SARS-CoV-2 and COVID-19 (32)

Nature Rev Immunol @NatRevImmunol: Our current understanding of the immunology behind #LongCovid, a comprehensive Review by @Daltmann10, Emily M. Whetlock, Siyi Liu, Deepa J. Arachchillage and @BoytonRosemary
Diagram ( https://twitter.com/NatRevImmunol/status/1678740068754653184/photo/1 )

Daniel M. Altmann et al. 2023. The immunology of long COVID ( Review Article). Nature Reviews Immunology (11 July 2023) https://www.nature.com/articles/s41577-023-00904-7

Abstract
Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia {autonomic dysfunction}. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.

...The oncoming burden of long COVID faced by patients, health-care providers, governments and economies is so large as to be unfathomable, which is possibly why minimal high-level planning is currently allocated to it. If 10% of acute infections lead to persistent symptoms, it could be predicted that ~400 million individuals globally are in need of support for long COVID. The biggest unknowns remain the joined-up scheme of its pathogenesis and thus the best candidate therapeutics to be trialled in randomized controlled trials, along with a better understanding of the kinetics of recovery and the factors influencing this. Some countries have invested in first-round funding for the pilot investigations. From the above, far more will be needed.

Harry Spoelstra @HarrySpoelstra | 4:50 AM · Jul 13, 2023
CardioVascular Surgeon, international clinical research, spin-offs, peer-Reviewer

Study: "SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis"

❗The good news: Colleagues are waking up
❗The bad news: They’re baffled and have as yet also no solution, but resort to definition bla, bla and surprise.....they call for PREVENTION!😷

➡️"This work has contributed to understanding the natural history and prevalence of PASC for previously hospitalised patients with SARS-CoV-2 infection up to 12 months after hospital discharge"
➡️"A significant proportion of infected individuals have persistent symptoms for a long period after acute infection"
➡️"Even in an era of SARS-CoV-2 vaccination and viral evolution, PASC continues to be reported in a substantial proportion of individuals"
➡️"but lack of symptom patterns and biomarkers have been barriers to defining this clinical entity"
➡️"Nonetheless, PASC poses a significant clinical, psychosocial and economic burden on society, underscoring the need for deeper clinical phenotyping and more pathogenesis studies, both of which will inform the definition of PASC while developing prevention(= Why didn't I think of this one 🤔) and treatment strategies"
➡️"As this study included data only from previously hospitalised patients, future analyses should consider both hospitalised and non-hospitalised patients to ensure that the results are more broadly generalisable to all infected individuals"

J. Daniel Kelly et al. 2023. SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis. European Respiratory Review 2023 32: 220254; DOI: 10.1183/16000617.0254-2022 https://err.ersjournals.com/content/32/169/220254

COVID and LC patients w anosmia:

Lorenzo Lupi et al 2023. Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis. Front. Immunol. 14 July 2023. Sec. Viral Immunology, Vol. 14-2023 | https://DOI.org/10.3389/fimmu.2023.1148595

{Will fix link when crummy internet permits. In mean time, one can google title plus the word "scholar" or try search at journal "Frontiers in Immunology".}

Fiona P. Havers et al. 2022. COVID-19-Associated Hospitalizations Among Vaccinated and Unvaccinated Adults 18 Years or Older in 13 US States, January 2021 to April 2022. JAMA Intern Med. September 8, 2022;182(10):1071-1081. doi:10.1001/jamainternmed.2022.4299 https://jamanetwork.com/.../jamainter.../fullarticle/2796235

Key Points
Question How do COVID-19–associated hospitalization rates compare among adults who are unvaccinated and vaccinated, and what are the risk factors for hospitalization for COVID-19 among vaccinated persons?

Findings In this cross-sectional study of US adults hospitalized with COVID-19 during January 2022 to April 2022 (during Omicron variant predominance), COVID-19-associated hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Compared with unvaccinated hospitalized persons, vaccinated hospitalized persons were more likely to be older and have more underlying medical conditions.

Meaning The study results suggest that COVID-19 vaccines are strongly associated with prevention of serious COVID-19 illness.

ABSTRACT
...Conclusions and Relevance In this cross-sectional study of US adults hospitalized with COVID-19, unvaccinated adults were 10.5X more likely to be hospitalized compared with vaccinated adults; hospitalization rates were lowest in those who had received a booster dose. Hospitalized vaccinated persons were older average 70 v 58 YO and more likely to have 3 or more underlying medical conditions and be long-term care facility residents compared with hospitalized unvaccinated persons...

SARS-CoV-2 Omicron subvariants BA.1 and BA.2 partially attenuated = reduced pathogenicity.
BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease.
Suggests that evolving Omicron subvariants can lose attenuation, at least partially.

Markus Hoffmann et al. 2023. Omicron subvariant BA.5 efficiently infects lung cells. Nature Communications volume 14, Article number: 3500 (13 June 2023) https://www.nature.com/articles/s41467-023-39147-4

Abstract
The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.

From Asymptomatic Covid to Long Covid: Major Advances in Genetic Underpinnings
Eric Topol (Scripps) | Jul 19, 2023

Today in Nature a groundbreaking and compelling report on the genomics of why some people do not manifest symptoms of Covid. And last week 2 papers... on the genetics of Long Covid. This represents genetic probes for the extreme of the clinical spectrum—from not exhibiting symptoms of SARS-CoV-2 infection to developing a debilitating, chronic condition. In this edition of Ground Truths, I’ll review the 3 new studies and contextualize their importance.

The Genomics of People Without Symptoms of Covid
...an immune function human leukocyte antigen (HLA) locus—HLA-B*15:01—was strongly associated with lack of developing symptoms....the odds ratio for asymptomatic to symptomatic was ~2.5-fold for this allele

The Genomics of Long Covid
...The risk of the key FOXP4 locus variant, with an allele frequency of 4.2%, was, in aggregate, 1.6-fold for its association with Long Covid...

In Context
More than 3 years into our exposure to SARS-CoV-2 we are seeing critically important progress to understand the marked heterogeneity of why some people, even after evidence of infection, escape Covid illness, while others develop a protracted, often quite debilitating condition. Our understanding of the biology of protection from Covid illness or increased susceptibility to Long Covid are still incomplete, but we are seeing some major advances in understanding. The protective HLA-B*15:01 allele finding is particularly striking, with additional T cell functional experiments to help point to cause and effect, and the impact of 2 copies of this variant carrying a more than 8-fold odds of remaining asymptomatic. On the other hand, the FOXP4 variant discovery, while derived from aggregating many studies and showing consistency across them for a 60% increased risk of Long Covid, remains more at the association level rather than established as a causal variant. These studies are not easy to do, because they entail accurate phenotyping of large numbers of participants (both phenotypes here of Asymptomatic and Long Covid are not straightforward), getting their biosamples and assaying their genomic data, and carrying out functional studies to interrogate the gene variants that are statistically significant. The work, however, has helped us to get to the basis of these conditions, and even further, for asymptomatic Covid, to guide us to better treatments and vaccines for the future. There will be more genomic loci that are validated in the future for both conditions as more GWAS and functional genomic studies are reported. It is exciting to unravel why our response to this virus is so variable, and hopefully steady progress will tell us more on how we can help people from ever getting ill or prevent the chronic condition from this virus.

https://erictopol.substack.com/p/from-asymptomatic-covid-to-long-covid
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Danillo G. Augusto et al. 2023. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature 19 July 2023. https://www.nature.com/articles/s41586-023-06331-x

Vilma Lammi 2023. Genome-wide Association Study of Long COVID (PREPRINT). medRxiv 1 July 2023. https://www.medrxiv.org/content/10.1101/2023.06.29.23292056v1

Krystyna Taylor et al. 2023. Genetic Risk Factors for Severe and Fatigue Dominant Long COVID and Commonalities with ME/CFS Identified by Combinatorial Analysis (PREPRINT). medRxiv 13 July 2023.
doi: https://doi.org/10.1101/2023.07.13.23292611 https://www.medrxiv.org/content/10.1101/2023.07.13.23292611v1

Study: 1 in 6 kids have persistent COVID symptoms for 3 months after infection (News brief)
Stephanie Soucheray | July 21, 2023

A systematic review today in Pediatrics of 31 studies published through December 2022 reveals that persistent symptoms 3 months after confirmed COVID-19 infections, or "long COVID," affect 16% of children and adolescents.

...Symptoms included fatigue, depression, sleep disturbance, cough, throat pain, and gastrointestinal symptoms.

The three most common persistent symptoms seen in the studies were sore throat...14.8%...; persistent fever...10.9%...; and sleep disturbance...10.3%...

https://www.cidrap.umn.edu/covid-19/study-1-6-kids-have-persistent-covid-symptom...
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Li Jiang et al. 2023. A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population (Review). Pediatrics e2022060351. July 21 2023. https://doi.org/10.1542/peds.2022-060351 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-060351/192...

Conclusions

We found less than one fifth of children and adolescents with a confirmed COVID-19 diagnosis continue presenting with at least 1 persistent clinical feature that cannot be explained by alternative diagnosis beyond 3 months after the acute phase of infection. Long COVID in children and adolescents has been reported with a very wide symptom spectrum and with great heterogeneity among studies included in this review. The presentation of long COVID may change with time. There is the need for high quality, prospective, and well controlled studies to address these issues. In the interim, preventing COVID-19 infection and vaccinations for children and adolescents must remain a priority.

JWeiland @JPWeiland | 7:17 PM · Jul 20, 2023:
Scientist. Infectious disease modeler.

Model for next 5 weeks:
Anticipating increases into August {US}, driven by EG.5.1, FL.1.5, and XBB.1.16.6.
Each of these have advantage over XBB.1.16, XBB.2.3 etc.
The lack of cases for the last 4 months is expected to have increased the number of people susceptable to infection.

US COVID Projections 18 July 2023 ( https://twitter.com/JPWeiland/status/1682167805553041408/photo/1 )

Raj Rajnarayanan @RajlabN | 4:32 AM · Jul 25, 2023:
Assistant Dean of Research and Associate Professor, NYITCOM at Arkansas State University

Just updated the KFF #LongCOVID chart with current data
The number of people currently experiencing #LongCOVID is not declining!

Source:
1) https://kff.org/policy-watch/long-covid-what-do-latest-data-show/
2) https://data.cdc.gov/NCHS/Post-COVID-Conditions/gsea-w83j

Bar graph, % people having/ever had LC, June 2022-July 2023 ( https://twitter.com/RajlabN/status/1683756990277750784/photo/1 )

NIH COVID-19 Treatment Guidelines:
Special Considerations in Children
US National Institute of Health | Updated: July 21, 2023

Key Considerations
...Children with 1 or more of the following comorbidities are at risk of severe COVID-19: cardiac disease, neurologic disorders, prematurity (in young infants), diabetes, obesity (particularly severe obesity), chronic lung disease, feeding tube dependence, and immunocompromised status. Age ( less than 1 year and 10–14 years) and non-White race/ethnicity are also associated with severe disease.

...A small subset of children and young adults with SARS-CoV-2 infection may develop multisystem inflammatory syndrome in children (MIS-C). Many patients with MIS-C require intensive care management. The majority of children with MIS-C do not have underlying comorbidities.

...For a description of children who are considered to be at high risk of severe COVID-19 and the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for their treatment, see Therapeutic Management of Nonhospitalized Children With COVID-19*...

https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of...

* NIH COVID-19 Treatment Guidelines:
Therapeutic Management of Nonhospitalized Children With COVID-19
US National Institute of Health | Updated: December 28, 2022
https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of...
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Lisa #SafeEdForAll @Sandyboots2020 · Jul 23

Long Covid in children:
The cardiopulmonary, neurocognitive and Type 1 diabetes have been added in the latest NIH update with zero fanfare.

How are parents supposed to know about this stuff?

Carol L Hodgson and Tessa Broadley 2023. Long COVID—unravelling a complex condition (Comment. Corrected Proof) The Lancet Respiratory Medicine, Available online 17 July 2023.
https://doi.org/10.1016/S2213-2600(23)00232-1 https://www.sciencedirect.com/science/article/pii/S2213260023002321

Refers to
Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness
View PDF

Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations
View PDF

Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation
View PDF

My knees...

Arthritis and Long COVID: A Double Whammy
— Worse pain and less functional ability with lingering virus symptoms, patients say
John Gever | July 24, 2023

...individuals in Laval, Quebec, who had some type of arthritis and developed post-acute COVID symptoms following initial infection...Just over half of these patients said they had experienced moderately to severely increased susceptibility to fatigue, and 42% complained of markedly more breathlessness when climbing stairs...Some 37% indicated they now had moderately or severely increased pain.

While fewer than 20% of respondents graded pre-COVID mobility and activity status as poor, about half did so for their current abilities:

Mobility: pre-COVID 18.5% poor, with long COVID 45.7% poor
Usual activities: pre-COVID 9.3% poor, with long COVID 52.5% poor

Furthermore, the unemployment rate among respondents with long COVID doubled after infection (14.5% pre-COVID vs 28% with long COVID). For context, among respondents without long COVID, their rate of unemployment rose from 13.8% pre-COVID to 19.0% at the time of the survey.

"Prevention of COVID is key for persons with arthritis. However, for those who are infected with COVID and develop long COVID, there is a need to implement timely and effective interventions to improve functional status," (Debbie Ehrmann Feldman, PhD, of the University of Montreal, and Barbara Mazer, PhD, of McGill University) wrote...

https://www.medpagetoday.com/rheumatology/arthritis/105626
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Debbie Ehrmann Feldman and Barbara Mazer 2023. Long covid in persons with self-reported arthritis - symptoms, associated factors and functional limitations (Brief Report). Arthritis Care and Research, 23 July 2023. https://doi.org/10.1002/acr.25200 {Accepted, in edit} https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.25200

Abstract
...Results
In our sample, 53.5% (91) reported being troubled by ongoing symptoms at the time of completing the questionnaire (long covid) and the most frequent symptoms were: fatigue, myalgia, weakness, breathlessness, low mood, anxiety, and sleep disturbance. Factors associated with long covid were female sex, having been hospitalized for covid, and having at least one other chronic disease. Persons with long covid had substantial declines in function, notably in global health status, usual activities, mobility, personal care, and employment status. Also, 37% of those with long covid reported moderate to severe increase in pain.

Conclusion
Persons with arthritis who have long covid have substantial limitations in function compared to their pre-covid status. There is a need to implement effective interventions to improve functional status in persons with arthritis and long covid.

COVID-19, but not flu (A), alters respiratory epithelium.

Bonnie H. Yeung-Luk et al. 2023. SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human respiratory epithelial cells mediated by expression of spike protein (AHEAD OF PRINT). mBio, 28 July 2023. DOI: https://doi.org/10.1128/mbio.00820-23 https://journals.asm.org/doi/10.1128/mbio.00820-23

...IMPORTANCE: COVID-19 has caused a global pandemic affecting millions of people worldwide, resulting in a higher mortality rate and concerns of more persistent symptoms compared to influenza A. To study this, we compare lung epithelial responses to both viruses. Interestingly, we found that in response to SARS-CoV-2 infection, the cellular energetics changed and there were cell structural rearrangements. These changes in cell structure could lead to prolonged epithelial cell survival, even in the face of not working well, potentially contributing to the development of chronic symptoms. In summary, these findings represent strategies utilized by the cell to survive the infection but result in a fundamental shift in the epithelial phenotype, with potential long-term consequences, which could set the stage for the development of chronic lung disease or long COVID-19...

...METHOD
...SARS-CoV-2 and influenza A infection in human nasal cells
Human nasal cells at ALI air-liquid interface were infected with mock, SCV2 SARS-C0V-2/USA/HP7(27)/2020, and IAV A/Baltimore/R0243/2018 H3N2...

Aerosols, y'all:

Scientists develop breath test that rapidly detects COVID-19 virus
(Washington U School of Medicine in St Louis News Release)
Jim Dryden • July 31, 2023

Test results available in less than a minute

...a breath test that could become a tool for use in doctors’ offices to quickly diagnose people infected with the virus. If and when new strains of COVID-19 or other airborne pathogenic diseases arise, such devices also could be used to screen people at public events. The researchers said the breath test also has potential to help prevent outbreaks in situations where many people live or interact in close quarters — for example aboard ships, in nursing homes, in residence halls at colleges and universities or on military bases...

https://medicine.wustl.edu/news/scientists-develop-breath-test-that-rapidly-dete...
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Earlier:

https://engineering.wustl.edu/news/2023/Air-monitor-can-detect-COVID-19-virus-va...

Puthussery JV et al. 2023. Real-time environmental surveillance of SARS-CoV-2 aerosols. Nature Communications, July 10, 2023. Doi: 10.1038/s41467-023-39419-z https://www.nature.com/articles/s41467-023-39419-z

Deonandan @deonandan | 9:05 AM · Aug 3, 2023
Professor Raywat Deonandan. Epidemiologist, Health Sciences, uOttawa. Senior Fellow, Massey College.

I'm not an immunologist, just a data guy. But my reading of the data reaches same conclusion: there is no actual "paxlovid rebound", just COVID rebound, which happens with or without paxlovid. Infection is often biphasic, with 2 distinct symptom periods.

'Paxlovid Rebound' Isn't Real. It Never Was
Josh Bloom — January 11, 2023

Some doctors are alarmed by the blase attitude toward the Covid drug Paxlovid, quite different from when the drug first became available. What's going on? Some of the waning interest in the drug is because of the widespread use of the term "Paxlovid rebound," implying that there is something wrong with it. More likely, the problem is the term, not the drug...

https://www.acsh.org/news/2023/01/11/paxlovid-rebound-isnt-real-it-never-was-167...

Combination test for COVID-19, influenza A/B, RSV receives FDA 510(k) clearance
Joshua Fitch | Aug 3, 2023

...Through an Emergency Use Authorization (EUA) from the FDA, the test has been available since February. According to BD (medical technology company Becton, Dickinson and Company), each BD MAX System is “capable of analyzing hundreds of samples over a 24-hour period.” The test is an RT-PCR assay that makes the distinction between the conditions in approximately 2 hours through the “walkaway workflow” of the BD MAX System, allowing for minimal human interaction...

https://www.contemporarypediatrics.com/view/combination-test-for-covid-19-influe...

Eric Topol (Scripps) @EricTopol | 11:43 AM · Aug 4, 2023:

Relevant to schools starting up soon is a new report on K-12 2° #SARSCoV2 transmission. It is low (~2-3%), but significantly reduced w/masks (by 88%), vaccination (by 96%), increased 2.5 fold in classroom vs out-of-classroom

Highlighted abstract ( https://twitter.com/EricTopol/status/1687489376732037120/photo/1 )

Sandra B. Nelson et al. 2023. Prevalence and Risk Factors for School-Associated Transmission of SARS-CoV-2. JAMA Health Forum. 4 Aug 2023;4(8):e232310. doi:10.1001/jamahealthforum.2023.2310 https://jamanetwork.com/journals/jama-health-forum/fullarticle/2807905

ABSTRACT...Results
...In multivariable analysis, during F20/S21 (fall 2020, spring 2021 semesters), masking was associated with a lower odds of transmission compared with not masking (odds radio (OR), 0.12...). In F21, classroom exposure vs out-of-classroom exposure was associated with increased odds of transmission (OR, 2.47...); a fully vaccinated vs unvaccinated contact was associated with a lower odds of transmission (OR, 0.04...). In both periods, a higher SVI (Social Vulnerability Index, e.g., socioeconomic status, household characteristics--age, single parenting, disability, and English language proficiency--and minority status--race and ethnicity) was associated with a greater odds of transmission.

Conclusions and Relevance
In this study of Massachusetts schools, the SAR for SARS-CoV-2 among school-based contacts was low during 2 periods, and factors associated with transmission risk varied over time. These findings suggest that ongoing surveillance efforts may be essential to ensure that both targeted resources and mitigation practices remain optimal and relevant for disease prevention.

Long Covid: A parallel pandemic (19:40)
Knowable Magazine | Aug 8, 2022

Many people may never be able to put the pandemic behind them. They have long Covid, a catch-all term for illness that lingers long after a Covid-19 infection. More than 200 symptoms have been reported by patients, from hair loss and incontinence to severe tremors, anxiety, extreme fatigue and heart palpitations. “Even if the pandemic virus spread were to stop today, we still have tens of millions of people suffering long Covid,” says Yale immunologist Akiko Iwasaki. “That’s a parallel pandemic that’s happening, which is getting a lot less attention than the acute and severe Covid.”

In this video, we hear from people struggling with long Covid and what scientists have learned about the condition — or conditions — so far. Iwasaki explains long Covid’s diverse effects on the body — on the central nervous system, the gastrointestinal tract, the respiratory and cardiac systems, and more — and the search for biological origins. Long Covid is likely more than one disease, but without biomarkers that indicate who will get long Covid and the ways each case will manifest, personalizing treatments is challenging. The prevalence of long Covid has been a wake-up call, Iwasaki says, for society to investigate other syndromes that emerge after a viral infection.

https://www.youtube.com/watch?v=7lfGu_UA75A

Chiara Pozzi et al. 2023. Association between duration of SARS-CoV-2 positivity and long COVID. Clinical Infectious Diseases, ciad434, Accepted Manuscript. Published: 22 July 2023 https://doi.org/10.1093/cid/ciad434 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad434/7227950?log...

Abstract
In an observational study {March 2020 to April 2022}, we analyzed 1,293 healthcare workers previously infected with SARS-CoV-2, of which 34.1% developed long COVID. Using a multivariate logistic regression model, we demonstrate that the likelihood of developing long COVID in infected individuals rises with the increasing of duration of infection and that three doses of the BNT162b2 vaccine are protective, even during the Omicron wave.

Hiroshi Yasuda (保田浩志) @Yash25571056 | 9:06 PM · Aug 6, 2023:
Scientist & Professor (科学者&教授). {Hiroshima, Japan}

"The main symptoms of the new Omicron strain EG.5.1 are a sore throat, a runny nose, a blocked nose, sneezing, a cough without phlegm, a headache, a cough with phlegm, a hoarse voice, muscle aches and pains and an altered sense of smell..
However, shortness of breath, a loss of smell and a fever are no longer the main symptoms."

Fever is no longer the main symptom..

https://mirror.co.uk/news/uk-news/ten-symptoms-new-rising-covid-30643261

Mask recommendations for kids as well as adults:

11 of the Very Best KN95 Masks for COVID Protection Authentic, high-quality KN95 masks as recommended by doctors and Strategist editors.
Liza Corsillo | Updated Mar. 10, 2023

https://nymag.com/strategist/article/best-kn95-masks-for-covid-protection.html#k...

Michael Olesen 💉😷🇺🇸🇺🇦 @maolesen | 5:09 PM · Aug 6, 2023:
Epidemiologist and federal disaster medicine team member.
Minneapolis, MN

I've added a forecast model to the US COVID positivity rate from the reference lab, including a 95% confidence interval through the end of August.

Graph 5/202-2023 incl. forecast US COVID positivity ( https://twitter.com/maolesen/status/1688296326377709568 )

Laurie Garrett @Laurie_Garrett | 12:06 PM · Aug 7, 2023
Former Sr Fellow @CFR_org. Recipient of Pulitzer Prize, Polk (2Xs) and Peabody Awards. Author: IHeard TheSirensScream, TheComingPlague, Ebola & BetrayalofTrust.

Ultra-cool.
"We put together a 1-stop shop dashboard for #COVID19 metrics that you can check at any time for 1000s of US jurisdictions. We have wastewater levels, hospitalization rates & capacities, ICU census data, death rates, & some testing data."

Inside Medicine COVID-19 Metrics Dashboard
by Benjamin Renton | Updated: Aug 7, 2023
https://public.tableau.com/app/profile/benjamin.renton/viz/InsideMedicineCOVID-1...

Thanks for continuing to aggregate a mass of great information.
Fwiw, I tried to utilize the above metrics dashboard, and didn’t get very far. I used mobile; will have to see if it performs better on a laptop.

>24 stellarexplorer: :) I thought vaccines would be the end of the story... But the seemingly endless permutations of this virus might be? And Long COVID, in a populace largely failing to protect itself?

People NEWLY positive for COVID needed for AT-HOME Pavlovid rebound study. Michael Mina is acclaimed scientist who discovered immune amnesia caused by measles (https://hms.harvard.edu/news/inside-immune-amnesia).

Michael Mina @michaelmina_lab | 7:14 PM · Aug 7, 2023:
https://twitter.com/michaelmina_lab/status/1688690215164973057

We are studying COVID rebound, including Paxlovid rebound.

If you have tested positive within the past 2 days, please take a look below.

A Fully at-home study that sends everything to your house and compensates for your time/energy/participation

https://redcapstsi.scripps.edu/redcap/surveys/?s=J83NTFYFHAJTXELY&utm_id=eMe...
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Even the home blood collection is a super simple at home collection called Tasso. It's a cool device, IMO
See picture here:
https://twitter.com/michaelmina_lab/status/1688668089813004288/photo/1

US COVID tracking shows another slight rise, increasing EG.5 proportion
Lisa Schnirring | August 7, 2023

With levels still very low, some indicators federal health officials use to track COVID-19 activity, such as hospitalizations and emergency department (ED) visits showed more small rises, according to the latest data from the Centers for Disease Control and Prevention (CDC).

Meanwhile, in its latest variant proportion update, the EG.5.1 Omicron subvariant, a descendant of XBB.1.9.2, continues its steady rise.

Most markers show more small rises for fourth straight week

Hospitalizations...were up 12.1% compared to a week ago. ...Deaths from COVID, another key indicator, remained level, with the virus linked to only 1% of deaths...

...ED visits rose 21.8% compared to a week ago, but as a whole, COVID infections make up only 1% of all ED visits. Increases were more marked in a handful of southeastern states, with Mississippi and Alabama reporting substantial increases from a week ago, and Louisiana and Florida reporting moderate increases.

Test positivity, another early marker, rose 1.3% compared to a week ago and is at 8.9% nationally. However, test positivity was higher in certain parts of the country, including the south-central states, southeastern states, and a portion of the northeast.

Wastewater tracking also reflects more rises, with all regions seeing a consistent rise with projected infections daily infections back to medium levels compared to the earlier Omicron months...

EG.5 noses ahead of XBB.1.16
...EG.5.1 showing another steady rise, now at an estimated 17.3% of sequences, up from 11.9% in the CDC's projections 2 weeks ago. EG.5.1 has now nudged ahead of XBB.1.16...

Other subvariants showing rising proportions in the United States include FL.1.5.1, which is at 8.6%, and XBB.1.16.6, at 7.7%.

Eric Topol, MD, director of the Scripps Research Translational Institute, said yesterday on his "Ground Truths" Substack blog that the EG.5.1 variant has shown a near doubling over the past few weeks...not clear if the rise in EG.5.1 is contributing to upward trends in the United States and when the rise will peak, Topol said, noting that the rise is noteworthy and concerning, but not to the level of the Omicron surge.

Topol pointed to concerns about a spike mutation in EG.5.1 and another variant that has a key spike mutation, F456L, that is part of mutation combination that can bind more tightly to ACE2, the cell receptor for the virus. He also referenced concerns scientists have that the "Flip" mutation combination could lead to a further reduction in neutralizing antibodies. So far, the prevalence of viruses that have the Flip combination is low globally, though Spain and Brazil are among the countries already seeing rises.

The nation isn't ready for EG.5.1 or impacts from viruses that have the Flip combination, Topol emphasized, citing concerns that the updated COVID vaccines won't be available until October. "We need to get serious about getting the new XBB.1.5 boosters out ASAP, and getting Project NextGen in high gear," he wrote. Project NextGen is a $5 billion Biden administration plan to speed the development of new COVID vaccines and treatments.

Experts have been pushing for better COVID vaccines, including ones that can curb transmission. ...

https://www.cidrap.umn.edu/covid-19/us-covid-tracking-shows-another-slight-rise-...

Michael Olesen 💉😷🇺🇸🇺🇦 @maolesen | 2:44 PM · Aug 6, 2023:
Epidemiologist and federal disaster medicine team member.
Minneapolis, MN

This is the reference lab I use for the antigen positivity rates in my state charts. I've created a graph for this for the entire country. We are in trouble.

Graph positivity May 2020-July 2023( https://twitter.com/maolesen/status/1688259766173229057/photo/1 )

Michael Mina @michaelmina_lab | 3:26 PM · Aug 8, 2023:

We are experiencing a surge in cases. Yes
Surprising? No
It’s happened ea year since ’20
Smaller surges (esp where A/C used) with peaks July/Aug
Then nationwide late fall/winter
It is a seasonal virus
This video puts in perspective

New U.S. COVID-19 Cases over Time (2:31)
This is "New U.S. COVID-19 Cases over Time" {Mar 2020 to July 2021}
SAVI | 2021
https://vimeo.com/466625351

Harry Spoelstra (cardiovascular surgeon) @HarrySpoelstra | 5:39 AM · Aug 10, 2023

Impacts of the COVID-19 pandemic on life expectancy at birth in Asia
Many other countries, outside Asia, should take note of the conclusions!

➡️"The COVID-19 pandemic had significantly affected e0 of Asian populations, and most contribution to the reduction of e0 came from the three older age groups, 60–79 years, 80 + years, and 45–59 years, with great variations across countries/territories"

➡️"Males suffered more losses than females in this pandemic"

➡️Important implications for development of more resilient public health systems in Asian societies with better policy interventions for vulnerable demographic groups.

Study: January 1, 2020 to December 31, 2021.

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-16426-9
Figure 2. ( https://twitter.com/HarrySpoelstra/status/1689572202834702336/photo/1 )

...

Eric Topol (Scripps MD-scientist) @EricTopol | 11:50 AM · Aug 9, 2023:

More than 3 years in, with tens of millions of people still suffering, this is the comprehensive list of validated treatments for #LongCovid, as established through rigorous, randomized clinical trials

Image ( https://twitter.com/EricTopol/status/1689303073494335488/photo/1 )

CIDRAP, U Minnesota: SARS-CoV-2 can damage mitochondrion in heart, other organs, study finds. Mitochondrial dysregulation leads to long-term damage and may help explain long COVID, the authors say.

SARS-CoV-2 can damage mitochondrion in heart, other organs, study finds
Mary Van Beusekom

...Research identifies potential therapeutic target

In autopsy tissue, mitochondrial gene expression had recovered in the lungs, but not in the heart, kidneys, and liver. The rodent tissue and measurement of the time of peak viral load in the lungs showed that mitochondrial gene expression was suppressed in the cerebellum, even though SARS-CoV-2 wasn't found in the brain. The cerebellum coordinates and regulates muscle activity.

Other animal models showed signs of recovery of mitochondrial function in the lungs during the mid-phase of COVID-19 infection.

Co-senior author Douglas Wallace, PhD, of CHOP, said that the study offers strong evidence that COVID-19 is a systemic disease that affects multiple organs rather than strictly an upper respiratory illness. "The continued dysfunction we observed in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to the internal organs of these patients," he said in the release.

The results also identified a potential therapeutic target, microRNA 2392, which was shown to regulate mitochondrial function in the human tissue samples, said co-senior author Afshin Beheshti, PhD, president of COV-IRT and a visiting researcher at the Broad Institute.

"This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see," he said. "Neutralizing this microRNA might be able to impede the replication of the virus, providing an additional therapeutic option for patients who are at risk for more serious complications related to the disease."

The researchers said they will use these data to conduct future studies on how systemic immune and inflammatory responses may lead to more severe illness in some patients.

https://www.cidrap.umn.edu/covid-19/sars-cov-2-can-damage-mitochondrion-heart-ot...
-----------------------------------------------------

Joseph W. Guarnieri et al. 2023. Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts. Science Translational Medicine 9 Aug 2023, Vol 15, Issue 708. DOI: 10.1126/scitranslmed.abq1533 https://www.science.org/doi/10.1126/scitranslmed.abq1533

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)–encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

Long covid has derailed my life. Make no mistake: It could yours, too.
Madeline Miller | August 9, 2023

...So how long am I going to do this? {mask, etc.} Until indoor air is safe for all, until vaccines prevent transmission, until there’s a cure for long covid. Until I’m not risking my family’s future on a grocery run. Because the truth is that however immortal we feel, we are all just one infection away from a new life.

GIFT LINK?
https://www.washingtonpost.com/opinions/2023/08/09/madeline-miller-long-covid-po...

Aiyiyi...

Long COVID is devastating and far from rare. As infections rise again, why are we still ignoring it?
As COVID cases rise once again, we are unprepared for the "mass disabling" event caused by long COVID
Philip Finkelstein | August 13, 2023

...an alarming scientific pattern is revealing itself across intersecting areas of research, which suggests that long COVID could be linked to neurodegenerative diseases like Parkinson's – having to do with the misfolding of alpha-synuclein proteins in the human nervous system...

https://www.salon.com/2023/08/13/long-is-devastating-and-far-from-rare-as-infect...
-------------------------------------------

Decrease risk of Long COVID with vaxx and masks, etc. Take Paxlovid and METFORMIN ASAP after infection suspected/confirmed. Contact your MD for Rx ASAP! (In some places, pharmacists may be able to test and prescribe?)

Carolyn T Bramante et al. 2023. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. The Lancet Infectious Diseases. Published:June 08, 2023 DOI:https://doi.org/10.1016/S1473-3099(23)00299-2 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00299-2/fullt...

Summary...Interpretation
Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.

Aiyiyiyi... "A potential role of SARS-CoV-2 in triggering the reactivation of other viruses, such as HHV-6, HHV-7 and Epstein-Barr virus has been hypothesized...(we) speculat(e) on a possible role of SARS-CoV-2 in the reactivation of human herpes virus-8 (HHV-8) infection."

Kaposi's sarcoma was seen in first AIDS patients. Both HIV and SARS-CoV-2 affect T cells? Granted, in this case, the recovering COVID patient was 83, and though rare, Kaposi's sarcoma was seen in the elderly, before the AIDS pandemic?

Francesca Magri et al. 2021. New-onset cutaneous kaposi's sarcoma following SARS-CoV-2 infection (Case Report). J Cosmet Dermatol. 2021 Dec;20(12):3747-3750. DOI: 10.1111/jocd.14549

Background: COVID-19 is associated with several cutaneous manifestations, including chilbain-like lesions, urticaria, erythema multiforme, and maculopapular lesions. Dermatoses may be directly linked to the viral infection or also represent a consequence of systemic therapies administrated for COVID-19. A potential role of SARS-CoV-2 in triggering the reactivation of other viruses, such as HHV-6, HHV-7 and Epstein-Barr virus has been hypothesized.

Objective: To better understand and hypothesize possible pathogenetic correlations of COVID-19 with other dermatological conditions.

Methods: We report the case of an 83-year-old woman hospitalized in a nursing home for several years. On November 2020, the patient had been diagnosed with SARS-CoV-2 infection, with repeated positive swabs until January 2021. After a month, new-onset asymptomatic cutaneous purplish macular lesions and violaceous patches occurred bilaterally on the feet.

Results: An incisional cutaneous biopsy and the histological examination of the plantar lesion revealed the diagnosis of Kaposi Sarcoma.

Conclusion: We report a unique case of new-onset bilateral Kaposi's sarcoma following COVID-19, speculating on a possible role of SARS-CoV-2 in the reactivation of human herpes virus-8 (HHV-8) infection.

Against transmission, think ventilation- government health advice from France
Contre la transmission, pensons aération !

From Ministère de la Santé et de la Prévention

0:30 ( https://twitter.com/Orla_Hegarty/status/1691523458385981440 )

- Orla Hegarty @Orla_Hegarty |2:53 PM · Aug 15, 2023
Architect Asst Professor @UCDDublin @UCDArch

Nate Bear @NateB_Panic | 6:17 AM · Aug 17, 2023:
Public health, climate, ecology, plausible futures.

Covid caused the biggest worldwide drop in life expectancy in modern history. When people say we overreacted to covid, I'd like to know where they wanted these lines to end up

Graph shows life expectancy 1962 to 2021 with the largest 2-year drop in modern history on every continent bar Australia-New Zealand coming in 2020 and 2021

Graph ( https://twitter.com/NateB_Panic/status/1692118489853497503/photo/1 )
----------------------------------------------

Cdn excess deaths

https://www.theglobeandmail.com/canada/article-excess-deaths-covid-canada/

Akiko Iwasaki (Yale): "nanoparticles poly(amine-co-ester) PACE can be used to deliver mRNA as a 👃🏼 #mucosal nasal vaccine to protect mice from lethal SARS-CoV-2 challenge."

Alexandra Suberi et al. 2023. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 16 Aug 2023 Vol 15, Issue 709
DOI: 10.1126/scitranslmed.abq0603 https://www.science.org/doi/10.1126/scitranslmed.abq0603

Editor’s summary
The ability to efficiently deliver mRNA to the lung would have applications for vaccine development, gene therapy, and more. Here, Suberi et al. showed that such mRNA delivery can be accomplished by encapsulating mRNAs of interest within optimized poly(amine-co-ester) polyplexes. Polyplex-delivered mRNAs were efficiently translated into protein in the lungs of mice with limited evidence of toxicity. This platform was successfully applied as an intranasal SARS-CoV-2 vaccine, eliciting robust immune responses that conferred protection against subsequent viral challenge. These results highlight the potential of this delivery system for vaccine applications and beyond. —Courtney Malo

Harry Spoelstra @HarrySpoelstra | 6:48 AM · Aug 17, 2023
CardioVascular Surgeon, international clinical research...

IMPORTANT:
The very special newly discovered Omicron variant has just been designated as: BA.2.86

https://github.com/cov-lineages/pango-designation/issues/2183

2nd-Generation BA.2 Saltation Lineage, ~31 spike mutations (3 seq, 2 countries, Aug 14) · Issue...
Description Sub-lineage of: BA.2 Earliest sequence: 2023-7-24, Denmark Most recent sequence: 2023-7-31; Denmark & Israel Countries circulating: Denmark (2), Israel Number of Sequences: 3 GISAID...

Londoners:

Danny Altmann @Daltmann10 | 6:15 AM · Aug 17, 2023
Immunology Prof. Ed at OUP OxfordOpenImmunol, Imperial Coll research group with @BoytonRosemary. Co-author - https://linktr.ee/thelongcovidha

WILCO Study update: would you like to help with #LongCovid research and can get to London for a blood test? We have a big push to recruit people infected during Omicron waves and either now have Long Covid, or fully recovered inside 4wks.

AltmannLongCovidStudy@imperial.ac.uk

Ad: WILCO Long Covid study ( https://twitter.com/Know_HG/status/1514693211259875334/photo/1 )

Australia

‘A death sentence’: More than 600 people die after catching COVID in hospital
By Henrietta Cook
June 26, 2023 — 5.00am

At least 659 Victorians have died after catching COVID-19 while being treated for other conditions in hospitals, with doctors warning that patients are delaying care over infection fears.

Health Department data obtained under freedom of information laws reveals 5614 people were suspected to have caught COVID while in the state’s public hospitals between 2020 and April this year...

https://www.theage.com.au/national/victoria/a-death-sentence-more-than-600-peopl...

Harry Spoelstra @HarrySpoelstra | 12:49 PM · Aug 16, 2023:
CardioVascular Surgeon, international clinical research...

❗️"Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events"
➡️Remember...you only have one heart, one life!

Quote
Emmanuel @ejustin46 · 20h:
SARS-CoV-2 infection triggers pro-atherogenic inflammatory 1 responses in human coronary vessels
"COVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection."

Graphs, figures, tables ( https://twitter.com/ejustin46/status/1691846529441562663/photo/1 )
-----------------------------------------------

Natalia Eberhardt et al. 2023. SARS-CoV-2 infection triggers pro-atherogenic inflammatory 1 responses in human coronary vessels. BioRxiv 15 Aug 2023. doi: https://doi.org/10.1101/2023.08.14.553245 https://biorxiv.org/content/10.1101/2023.08.14.553245v1

This article is a preprint and has not been certified by peer review

Abstract
COVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection. While the systemic inflammatory response to SARS-CoV-2 infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques to locally promote inflammation remains unknown. Here, we report that SARS-CoV-2 viral RNA (vRNA) is detectable and replicates in coronary atherosclerotic lesions taken at autopsy from patients with severe COVID-19. SARS-CoV-2 localizes to plaque macrophages and shows a stronger tropism for arterial lesions compared to corresponding perivascular fat, correlating with the degree of macrophage infiltration. In vitro infection of human primary macrophages highlights that SARS-CoV-2 entry is increased in cholesterol-loaded macrophages (foam cells) and is dependent, in part, on neuropilin-1 (NRP-1). Furthermore, although viral replication is abortive, SARS-CoV-2 induces a robust inflammatory response that includes interleukins IL-6 and IL-1β, key cytokines known to trigger ischemic cardiovascular events. SARS-CoV-2 infection of human atherosclerotic vascular explants recapitulates the immune response seen in cultured macrophages, including proatherogenic cytokine secretion. Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events.

Apparently Paxlovid doesn't head off serious disease in vaxxed folks? Does not engender confidence in Big Pharma OR govt that it's taken so long to get this info out. Maybe behind-the-scenes knowledge was behind failure to vigorously promote Paxlovid? (ETA: Doesn't seem to address Paxlovid reduction risk of Long Covid, per other studies, so I'd still take Paxlovid until I hear otherwise on LC.)

Andrew Morris @ASPphysician | 3:12 PM · Aug 15, 2023:
Paxlovid: a drug that does nothing to help low-risk patients.

Took over a year to post study on http://ClinicalTrials.gov after study completion and still no scientific publication available.
https://clinicaltrials.gov/study/NCT05011513?term=Epic%20sr&rank=1&tab=r...
-------------------------------------------

Jake Scott, MD @jakescottMD
The results from the only randomized controlled trial that studied Paxlovid in vaccinated people (EPIC-SR) are finally available: no evidence that it provides any benefit.

Good thing immune protection against serious illness has remained so robust.

Quote Todd C. Lee @DrToddLee · Aug 15
Epic-sr results quietly posted on CT dot gov.
Thanks for the tip @jpogue1...

https://clinicaltrials.gov/study/NCT05011513?term=Epic%20sr&rank=1&tab=r...

LC patients' successful promotion of concerns may benefit other sufferers of similarly obscure conditions going forward, e.g., Lyme, Chronic Fatigue Syndrome:

Melody Turner et al. 2023.The #longcovid revolution: A reflexive thematic analysis . Social Science & Medicine
Volume 333, September 2023, 116130
https://doi.org/10.1016/j.socscimed.2023.116130 https://sciencedirect.com/science/article/pii/S0277953623004872?via%3Dihub

Highlights
• Twitter users socially constructed long COVID by sharing 31,000+ tweets.
• Long COVID symptoms were described as multi-system and cyclical.
• These symptoms gained social consensus on Twitter.
• This social consensus led to a collective social movement.
• The movement identified and campaigned for long COVID healthcare needs.

Abstract
Research has identified long COVID as the first virtual patient-made condition (Callard and Perego, 2021). It originated from Twitter users sharing their experiences using the hashtag #longcovid. Over the first two years of the pandemic, long COVID affected as many as 17 million people in Europe (WHO, 2023). This study focuses on the initial #longcovid tweets in 2020 (as previous studies have focused on 2021–2022), from the first tweet in May to August 2020, when the World Health Organization recognised the condition.

We collected over 31,000 tweets containing #longcovid from Twitter. Using Braun and Clarke's reflexive thematic analysis (2020), informed by the first author's experience of long COVID and drawing on Ian Hacking's perspective on social constructionism (1999), we identified different grades of social constructionism in the tweets. The themes we generated reflected that long COVID was a multi-system, cyclical condition initially stigmatised and misunderstood. These findings align with existing literature (Ladds et al., 2020; Rushforth et al., 2021).

We add to the existing literature by suggesting that Twitter users raised awareness of long COVID by providing social consensus on their long COVID symptoms. Despite the challenge for traditional evidence-based medicine to capture the varied and intermittent symptoms, the social consensus highlighted that these variations were a consistent and collective experience. This social consensus fostered a collective social movement, overcoming stigma through supportive tweets and highlighting their healthcare needs using #researchrehabrecognition. The #longcovid movement's work was revolutionary, as it showed a revolutionary grade of social constructionism, because it brought about real-world change for long COVID sufferers in terms of recognition and the potential for healthcare provisions.

Twitter users' accounts expose the limitations of traditional evidence-based medicine in identifying new conditions. Future research on novel conditions should consider various research paradigms, such as Evidence-Based Medicine Plus (Greenhalgh et al., 2022).

Image ( https://twitter.com/HarrySpoelstra/status/1691740045156274512/photo/1 )

>44 margd: I don't think you should make any firm conclusions based on one study

>46 jjwilson61: Agreed that firm conclusions shouldn't rely on one study, but there are studies and there are studies, but the one cited in >44 margd: was a CLINICAL TRIAL!

I finally got to briefly review the CDC publication and it seems to restrict itself to serious acute disease and not to Long COVID so I'd still seek out Paxlovid if/when I get sick.

I'd also be asking my MD about taking metformin to head off serious disease #141 on thread 31:

Eric Topol (cardiologist, scientist, Scripps) @EricTopol | 1:35 PM · Mar 6, 2023:

Very good news
Metformin significantly helped prevent #LongCovid in a placebo-controlled randomized trial, a 42% relative reduction
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4375620 by @BramanteCarolyn and colleagues
Graph ( https://twitter.com/EricTopol/status/1632812104200908800/photo/1 )

Worked consistently across key subgroups
Table ( https://twitter.com/EricTopol/status/1632812109041119232/photo/1 )
-----------------------------------------------

Carolyn Bramante et al. 2023. Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months: A Multi-Center, Quadruple-Blind, Parallel Group Randomized Phase 3 Trial. SSRN,
24 Pages Posted: 6 Mar 2023. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4375620

PREPRINT. Not yet peer-reviewed.

Abstract
Background: Post-acute sequelae of COVID, termed “Long COVID”, is an emerging chronic illness potentially affecting ~10% of those with COVID-19. We sought to determine if outpatient treatment with metformin, ivermectin, or fluvoxamine could prevent Long COVID.

Methods: COVID-OUT (NCT04510194) was a decentralized, multi-site trial in the United States testing three medications (metformin, ivermectin, fluvoxamine) using a 2x3 parallel treatment factorial randomized assignment to efficiently share placebo controls. Participants, investigators, care providers, and outcomes assessors were masked to randomized treatment assignment. Inclusion criteria included: age 30 to 85 years with overweight or obesity, symptoms less than 7 days, enrolled within 3 or fewer days of documented SARS-CoV-2 infection. Long COVID diagnosis from a medical provider was a pre-specified secondary outcome assessed by monthly surveys through 300 days after randomization and confirmed in medical records.

Findings: Of 1323 randomized trial participants, 1125 consented for long-term follow up, and 95.1% completed more than 9 months of follow up. The median age was 45 years ..., and 56% were female (7% pregnant). The median BMI was 30 kg/m2 ... Overall, 8.4% reported a medical provider diagnosed them with Long COVID; cumulative incidence: 6.3% with metformin and 10.6% with matched placebo. The hazard ratio (HR) for metformin preventing Long COVID was 0.58...versus placebo. The metformin effect was consistent across subgroups, including viral variants. When metformin was started within less than 4 days of symptom onset, the HR for Long COVID was 0.37... No statistical difference in Long COVID occurred in those randomized to either ivermectin (HR=0.99...) or fluvoxamine (HR=1.36...).

Interpretations: A 42% relative decrease and 4.3% absolute decrease in the Long COVID incidence occurred in participants who received early outpatient COVID-19 treatment with metformin compared to exact-matching placebo.

...Conclusions
Outpatient treatment with metformin at the time of SARS-CoV-2 infection decreased the development of Long Covid by 42% in a phase 3 randomized trial, and by over 50% when started less than 4 days from symptom onset. This finding is consistent with the 42% reduction in healthcare utilization for severe Covid-19 with metformin in the first 14 days of the trial. Fluvoxamine and ivermectin did not decrease the development of Long Covid, which is consistent with outcomes in the first 14 days of the trial. These results are hihly {sic} relevant to the current state of the pandemic because the study sample was approximately half vaccinated, and despite the 10-month follow-up of these outcome, the trial enrolled during Omicron wave. Long Covid is a significant public health emergency that may have lasting health, mental health, and economic sequelae, especially in socioeconomically marginalized groups, and metformin is safe, low-cost, and widely available.

Jennifer Abbasi 2023. What to Know About EG.5, the Latest SARS-CoV-2 “Variant of Interest”. JAMA. Published online August 18, 2023. doi:10.1001/jama.2023.16498 https://jamanetwork.com/journals/jama/fullarticle/2808762

The Omicron descendant EG.5 is the latest to be labeled a “variant of interest” by the World Health Organization (WHO), joining the current ranks of XBB.1.16 and XBB.1.5. The new designation, made as part of an August 9 initial risk evaluation of the variant, reflects its “notable rise” in global prevalence during recent weeks...

It Has a Growth Advantage...
It Has Antibody Escape Properties...
It’s Unclear Whether It’s Driving the COVID Wave...
There’s No Indication It’s More Severe...
There’s Optimism About the Updated Vaccine Booster...

Eris {EG.5.1} and BA.2.86 {Pirola }: Do I need to worry about COVID again?
Deena Beasley and Nancy Lapid | August 19, 2023

...BA.2.86...has 36 mutations that distinguish it from the currently-dominant XBB.1.5 variant.

What is new about COVID?

What do scientists say about BA.2.86?
BA.2.86 stems from an "earlier branch" of the coronavirus, so it differs from the variant targeted by current vaccines...

...many countries have drastically reduced testing of patients and their efforts to analyze the genomes of the viruses causing new COVID cases. In that situation, the trajectory of BA.2.86 "doesn't look good right now," given the speed at which new cases are being identified, said Dr. Eric Topol, a genomics expert and director of the Scripps Research Translational Institute in La Jolla, California...many mutations make BA.2.86 "radically different in its structure" compared to earlier variants...The main question, he added, is whether BA.2.86 will turn out to be highly transmissible.

Do the new variants make people sicker?...too soon to know...

Will vaccines protect against new variants? ...defense against illness and death...Dr. S. Wesley Long, medical director of diagnostic microbiology at Houston Methodist Hospital. {BA.2.86 stems from an "earlier branch" of the coronavirus, so it differs from the variant targeted by current vaccines}

https://www.reuters.com/business/healthcare-pharmaceuticals/eris-ba286-do-i-need...

News Release: Long COVID still worrisome 2 years after infection
Kristina Sauerwein•August 21, 2023

Virus continues to pose risk of diabetes, lung problems, blood clots, GI issues, other conditions...

https://medicine.wustl.edu/news/long-covid-still-worrisome-2-years-after-infecti...

-------------------------------------------------------

Benjamin Bowe et al. 2023. Postacute sequelae of COVID-19 at 2 years. Nature Medicine (21 Aug 2023). https://www.nature.com/articles/s41591-023-02521-2

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 ... and 642.8 ... disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% ... and 21.3% ... of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.

Why a highly mutated coronavirus variant {BA.2.86 "Pirola"} has scientists on alert
Ewen Callaway | 21 August 2023

...linked to 6 cases in 4 countries: Israel, Denmark, the United Kingdom and the United States {Mich}. The {WHO} has designated BA.2.86 as a variant under monitoring.

...seems to be descended from an Omicron subvariant called BA.2, which caused large case spikes in early 2022. However, the BA.2.86 spike protein — the molecule that SARS-CoV-2 uses to enter cells — carries 34 changes relative to BA.2.

...there is a good chance that the variant will be able to escape some of the neutralizing antibodies triggered by previous infections and vaccine boosters.

...may already be fairly widespread

What do researchers want to find out? {distribution, immune evasiveness}

Should the public be concerned about BA.2.86?
...The appearance of BA.2.86 has caught scientists by surprise — and shows that SARS-CoV-2 still has more tricks up its sleeve that researchers will want to understand. “We’ll see if it’s important beyond that in terms of its public health impact,” says {Adam Lauring, a virologist and infectious-disease physician at the University of Michigan in Ann Arbor, whose lab identified one person infected with BA.2.86.}.

doi: https://doi.org/10.1038/d41586-023-02656-9
https://www.nature.com/articles/d41586-023-02656-9

Walgreen's COVID 19 index went private as US cases increased. Outcry.

CyFi @CyFi10 | 1:49 PM · Aug 21, 2023:
BREAKING: The Walgreens COVID-19 index is back, and has new data for this week!
California and Nevada set a new ALL TIME RECORD HIGH for positivity rate!

US current positivity map, graphs ( https://twitter.com/CyFi10/status/1693681660947317204/photo/1 )

US positivity changes fr previous week map, graphs ( https://twitter.com/CyFi10/status/1693681660947317204/photo/2 )

Nevada ( https://twitter.com/CyFi10/status/1693681660947317204/photo/3 )

California ( https://twitter.com/CyFi10/status/1693681660947317204/photo/4 )

Eric Topol @EricTopol | 2:15 PM · Aug 22, 2023

The US Project NextGen ($5B) vs Covid, to develop better, more durable, variant-proof vaccines, nasal vaccines, and effective monoclonal antibodies, is finally showing signs of life 👍👏

Screen shot HHS news release 22 Aug 2023 ( https://twitter.com/EricTopol/status/1694050723603050505/photo/1 )

News Release:
Project NextGen Awards Over $1.4 Billion to Develop the Future of COVID-19 Vaccines and Therapeutics
HHS | 22 Aug 2023

...the U.S. Department of Health and Human Services (HHS), through the Administration for Strategic Preparedness and Response (ASPR), awarded more than $1.4 billion for Project NextGen to support the development of a new generation of tools and technologies to protect against COVID-19 for years to come.

...The awards to BARDA’s Clinical Studies Network will speed the development of new vaccine candidates, providing a network of at-the-ready trials with the flexibility to pivot to the most promising new vaccines as they mature. The public can expect to see clinical trials for new vaccine candidates targeting longer-lasting protection against future variants as early as this winter under Project NextGen.

HHS’ partnership with Regeneron is advancing its efforts to prevent COVID-19 infections by developing a novel monoclonal antibody that will protect people who do not respond to or cannot take existing vaccines – a critical need and current gap in COVID-19 therapeutics. HHS and Regeneron expect that the new monoclonal antibody will enter clinical trials this fall.

The remaining awards will fund technologies that enable more efficient development and manufacturing strategies – accelerating development timelines across the board and bolstering future vaccine and therapeutic availability.

...HHS ... expects to announce additional awards before the end of this fiscal year...

https://www.hhs.gov/about/news/2023/08/22/funding-1-billion-vaccine-clinical-tri...

Risk Assessment Summary for SARS CoV-2 Sublineage BA.2.86 {Pirola}
CDC | August 23, 2023

Background
Current Risk Assessment
Prevention Actions
Scientific Understanding of BA.2.86 as of August 23, 2023

https://www.cdc.gov/respiratory-viruses/whats-new/covid-19-variant.html

Maxime Taquet t aal 2022. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. The Lancet Psychiatry, Volume 9, ISSUE 10, P815-827, October 2022. DOI:https://doi.org/10.1016/S2215-0366(22)00260-7 https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(22)00260-7/fullt...

Summary
...Findings: We identified 1 487 712 patients with a recorded diagnosis of COVID-19 during the study period, of whom 1 284 437 (185 748 children, 856 588 adults, and 242 101 older adults; overall mean age 42·5 years...; 741 806 (57·8%) were female and 542 192 (42·2%) were male) were adequately matched with an equal number of patients with another respiratory infection. The risk trajectories of outcomes after SARS-CoV-2 infection in the whole cohort differed substantially. While most outcomes had HRs {hazard ratios} significantly greater than 1 after 6 months (with the exception of encephalitis; Guillain-Barré syndrome; nerve, nerve root, and plexus disorder; and parkinsonism), their risk horizons and time to equal incidence varied greatly.

{Mood & anxiety} Risks of the common psychiatric disorders returned to baseline after 1–2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days).

{Acquired fog, dementia, pschosis, seizures} By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period.

{Children} Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 ...) or anxiety (1·00 ...) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 ... to 2·16 ...).

{Children} Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days).

{Over 65s} A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures.

{Alpha variant} Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort).

{Delta variant} Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate.

{Omicron variant} With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.

Interpretation: This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.

{Lead author responding to "Liberal arts major translation please?"}
Danny Altmann @Daltmann10 | 12:32 PM · Aug 24, 2023:
Quite a simple study! Some with #longcovid have speculated that their immunity when first infected may have been at fault, too high or low. We stratified healthcare workers from 1st wave into persistent symptoms or none, comparing antibody and T cell responses - no differences

DM Altmann et al. 2023. Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity. Nature Communications volume 14, Article number: 5139 (23 Aug 2023)
https://www.nature.com/articles/s41467-023-40460-1.epdf

COVID-19: examining the effectiveness of
non-pharmaceutical interventions
Executive summary
Royal Society 2023
20p
https://royalsociety.org/-/media/policy/projects/impact-non-pharmaceutical-inter...
-----------------------------------------

Lockdowns and face masks ‘unequivocally’ cut spread of Covid, report finds
PA Media | Thu 24 Aug 2023

Royal Society review looks at non-pharmaceutical interventions when applied in packages of several measures

...The review found social distancing and lockdowns were the most effective category of NPIs. Stay-at-home orders, physical distancing and restrictions on gathering size were repeatedly found to be associated with significant reduction in Sars-CoV-2 transmission. The more stringent the measures were the greater the effect they had, the experts found.

In care homes, measures such as cohorting and visitor restrictions were associated with reduced transmission and reduced outbreaks.

Additionally, the report found that in school settings, closures and other distancing measures were associated with reduced Covid-19 cases, but the effectiveness varied depending on a range of factors, including adherence and pupils’ ages.

When looking at the use of face masks and mask mandates, studies consistently reported the measures were an effective approach to reduce infection. The evidence further indicates higher-quality respirator masks – such as N95 masks – were more effective than surgical-type masks.

Assessing test, trace and isolate measures, studies from several countries which implemented high levels of contact tracing, with isolation of infected individuals and their contacts, found reductions in Covid-19 deaths.

For the future, the report recommends establishing international protocols for conducting clinical trials and observational research on NPIs in advance of further pandemics...

https://www.theguardian.com/world/2023/aug/24/lockdowns-face-masks-unequivocally...

Mike Hoerger, PhD MSCR MBA @michael_hoerger | 2:06 PM · Aug 24, 2023:
Founding Director of Louisiana's #HealthPsych PhD program.

Good news friends. Biobot #wastewater data suggest the late summer wave may have peaked nationally in the U.S. 🤞

This is consistent with the earlier PMC {Pub Med Central} forecasts, which I will update shortly.

Hopefully we're not resting at a crest before a larger school-induced peak.

Graph of Biobot wastewater data for the past 6 months ( https://twitter.com/michael_hoerger/status/1694773252059550058/photo/1)

"An estimated 1.87 million excess deaths occurred among individuals 30 years and older during the first 2 months after the end of China’s zero COVID policy"

Hong Xiao et al. 2023. Excess All-Cause Mortality in China After Ending the Zero COVID Policy. JAMA Netw Open. 24 Aug 2023;6(8):e2330877. doi:10.1001/jamanetworkopen.2023.30877 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808734

Key Points
Question Was the sudden end of China’s zero COVID policy associated with an increase in population all-cause mortality?

Findings In this cohort study across all regions in mainland China, an estimated 1.87 million excess deaths occurred among individuals 30 years and older during the first 2 months after the end of China’s zero COVID policy. Excess deaths predominantly occurred among older individuals and were observed across all provinces in mainland China, with the exception of Tibet.

Meaning These findings suggest that the sudden lifting of the zero COVID policy in China was associated with significant increases in all-cause mortality.

Laurie Garrett @Laurie_Garrett | 10:26 AM · Aug 24, 2023:
Former Sr Fellow @CFR_org. Recipient of Pulitzer Prize, Polk (2Xs) and Peabody Awards. Author: I Heard the Sirens Scream, The Coming Plague, Ebola and Betrayal of Trust.

As evidence mounts that #SARSCoV2 damages mitochondrial function inside human cells, thereby dampening the cellular energy flow, the wide range of #LongCovid symptoms start to make more sense...
-------------------------------------------------------------

NIH Research: SARS-CoV-2 can cause lasting damage to cells’ energy production
NIH | August 22, 2023

...The researchers also found a potential new target for treatment. They found that SARS-CoV-2 boosted expression of a regulatory molecule called miR-2392. This, in turn, lowered expression of mitochondrial genes involved in energy production...

http://dlvr.it/Sv58rN
--------------------------------------------------------------

Joseph W. Guarnieri et al. 2023. Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts. Science Translational Medicine, 9 Aug 2023, Vol 15, Issue 708. DOI: 10.1126/scitranslmed.abq1533 https://www.science.org/doi/full/10.1126/scitranslmed.abq1533

Editor’s summary
SARS-CoV-2 needs host cells to generate molecules for viral replication and propagation. Guarnieri et al. now show that the virus is able to block expression of both nuclear-encoded and mitochondrial-encoded mitochondrial genes, resulting in impaired host mitochondrial function. They analyzed human nasopharyngeal samples and autopsy tissues from patients with COVID-19 and tissues from hamsters and mice infected with SARS-CoV-2. Host cells attempt to compensate by activating innate immune defenses and mitochondrial gene expression, but chronically impaired mitochondrial function ultimately may result in serious COVID-19 sequelae such as organ failure. —Orla Smith
-------------------------------------------------------------
ETA

Study reveals how SARS-CoV-2 alters mitochondria, leading to energy outages and organ failure
31 Oct 2023

...The new findings also highlight new ways to address the mitochondrial dysfunction that occurs during COVID infection. Diet, exercise, natural compounds, or a combination of the three, may be able to stimulate mitochondrial function, but whether or not they are effective for patients with long COVID is yet to be known...

https://www.news-medical.net/news/20231031/Study-reveals-how-SARS-CoV-2-alters-m...

LC: one go-round was enough for me!

What the Latest Evidence Actually Says About Long COVID
Gideon Meyerowitz-Katz | Aug 25, 2023

A new study looks at data from patients two years after their initial infection. It contains some alarming figures—until you dig into them...

https://slate.com/technology/2023/08/long-covid-nature-medicine-public-health.ht...

>60 margd:

Jeff Gilchrist @jeffgilchrist | 7:55 AM · Aug 26, 2023:
PhD Biomedical researcher, data scientist, and finder of large prime numbers.

"an estimated 1.87 million excess deaths occurred among individuals 30 years and older during the first 2 months after the end of China’s zero COVID policy." - period was Dec. 2022 - Jan. 2023 ( https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808734 ) H/T: @anenigma420
1/2

Compare 1.87 million excess deaths that were missed to the 60,000 "official" deaths that was reported. Reuters story about the study ( https://reuters.com/world/china/nearly-2-million-excess-deaths-followed-chinas-s... ).
2/2

COVID Omicron carries 4 times the risk of death as flu, new data show
Mary Van Beusekom | August 25, 2023
https://www.cidrap.umn.edu/covid-19/covid-omicron-carries-4-times-risk-death-flu...
----------------------------------------

Edward Goldstein 2023. Mortality associated with Omicron and influenza infections in France before and during the COVID-19 pandemic (Accepted manuscript for Epidemiology & Infection). Published online by Cambridge University Press: 25 August 2023. DOI: https://doi.org/10.1017/S0950268823001358 https://www.cambridge.org/core/journals/epidemiology-and-infection/article/morta...

NG Gumanova et al. 2023. Effects of COVID-19 Infection in Healthy Subjects on Cardiac Function and Biomarkers of Oxygen Transport, Blood Coagulation and Inflammation. Viruses 25 July 2023, 15(8), 1623; https://doi.org/10.3390/v15081623 https://mdpi.com/1999-4915/15/8/1623

ABSTRACT
... Methods: The present cross-sectional study included 307 healthy volunteers (24–69 years of age...80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS ... to reveal 70 IgG-SARS-positive and 237 negative participants...

Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased ... in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants.

Conclusions: LV {left ventricle} filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. Our observations contribute to the definition of vulnerabilities in the apparently healthy subjects with long COVID-19. These vulnerabilities may be more severe in patients with certain chronic diseases.

·

Where we are in the pandemic (6:36)
The World | Aug. 25, 2023 ...

The COVID-19 pandemic was declared over in May this year, but a recent rise in cases and the spread of new variants is raising questions about what may be next. Host Carolyn Beeler speaks with Dr. Eric Topol, director of the Scripps Research Translational Institute, about a rise in new cases, concern about new variants, the state of vaccine production, and the potential impact of a new wave of infections in the colder months.

https://theworld.org/media/2023-08-25/where-we-are-pandemic

COVID-19 may trigger new-onset high blood pressure in high risk individuals
Dan Gray | August 21, 2023

...In an analysis of six-month follow-up data from more than 45,000 people who had COVID-19, researchers reported that 21% of people who were hospitalized for the virus and 11% who were not hospitalized later developed high blood pressure.

While similar effects happen with influenza – a similar respiratory infection – the numbers were higher across the board for people who’ve had COVID-19, the researchers reported...

https://www.medicalnewstoday.com/articles/covid-19-may-trigger-new-onset-high-bl...
--------------------------------------------------

Vincent Zhang et al. 2023. Incidence of New-Onset Hypertension Post–COVID-19: Comparison With Influenza. Hypertension, Originally published 21 Aug 2023. https://doi.org/10.1161/HYPERTENSIONAHA.123.21174. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.123.21174

Abstract
RESULTS:
At 6-month follow-up, new-onset persistent hypertension was seen in 20.6% of hospitalized patients with COVID-19 and 10.85% of nonhospitalized patients with COVID-19. Persistent hypertension incidence among hospitalized patients did not vary across the pandemic, whereas that of among hospitalized patients decreased from 20% in March 2020 to ≈10% in October 2020 ... and then plateaued thereafter. Hospitalized patients with COVID-19 were 2.23...times and nonhospitalized patients with COVID-19 were 1.52...times more likely to develop persistent hypertension than influenza counterparts. Persistent hypertension was more common among older adults, males, patients with preexisting comorbidities (chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease), and those who were treated with pressor and corticosteroid medications. Mathematical models predicted persistent hypertension with 79% to 86% accuracy. In addition, 21.0% of hospitalized patients with COVID-19 with no prior hypertension developed hypertension during COVID-19 hospitalization.

CONCLUSIONS:
Incidence of new-onset persistent hypertension in patients with COVID-19 is higher than those with influenza, likely constituting a major health burden given the sheer number of patients with COVID-19. Screening at-risk patients for hypertension following COVID-19 illness may be warranted.

Jeff Gilchrist @jeffgilchrist | 2:50 PM · Aug 27, 2023:
PhD Biomedical researcher, data scientist, and finder of large prime numbers.

This is why even non-perfect masking, improved ventilation and filtration are important since they might be able to get viral levels down enough to stop infection. Don't ignore things that are not 100% effective and go without any protection since it might just be enough.

Quote
Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 5:35 AM · Aug 27, 2023:
https://threadreaderapp.com/thread/1695731828206833769.html

A short 🧵on a recent study by @MaggieLind*2 with @MHitchingsEpi @datcummings Albert Ko et al. Data show that immunity induced by vaccines, prior infection or both (hybrid) protects against SARS-CoV-2 infection when viral exposure is low to moderate (1/)

Question being asked: What is the risk of becoming *infected* with SARS-CoV-2 after developing immunity following a vaccine, prior infection, or both if exposure to the virus is very high, moderate, or low? They did not study the severity of symptoms. (2/)

How? The authors used the existing database of the Connecticut Department of Correction, where infection data based on high frequency of testing for SARS-CoV-2 on ~9300 residents across 13 facilities were available. (3/)

What did they find? Prior infection, vaccination, or both provided significant protection against infection when the exposure was moderate (index case was within their cellblock) or low (no exposure was documented in cellblock co-residents) against Delta or Omicron. (4/)
Table ( https://twitter.com/VirusesImmunity/status/1695731836876419180/photo/1 )

However, when the viral exposure was intense (with infected cellmate - exposure is 24/7), none of these groups had enough immunity to protect against infection with Delta or Omicron virus. (5/)
Table ( https://twitter.com/VirusesImmunity/status/1695731842043777504/photo/1 )

These findings suggest that protection conferred by prior infection and vaccination is dependent on the cumulative viral exposure dose. An important question for the future is to determine how much the viral load vs. duration of exposure plays a key role. (6/)

If the protection is indeed dose-dependent, coupling non-pharmaceutical interventions with vaccination would be beneficial because the non-pharmaceutical intervention (masking, ventilation, etc..) reduces viral exposure, resulting in improved levels of conferred protection. (7/)

More broadly, this study answers a fundamental question on the nature of immunity. While the field speculated that immune protection against infection is exposure dose-dependent, data in support were limited. Now this study directly demonstrated this for COVID. (8/)

Their findings suggest the “need for layered interventions to mitigate SARS-CoV-2 spread, especially within dense settings, such as congregate settings, and in settings where prolonged contact is likely, such as households with infected people.” An important message to end 🧵
--------------------------------------------------------------

* Margaret L. Lind et al. 2023. Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population. Nature Communications volume 14, Article number: 5055 (19 Aug 2023). https://nature.com/articles/s41467-023-40750-8

... the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings...

Elite aquatic athletes surveyed after June/July 2022 intl championship without social distancing and w/o the imposition of an isolation “bubble”:

... 49.4% of athletes had experienced SARS-CoV-2 infection...infection rates varied significantly across different aquatic sports, with open water swimmers having the lowest (28%) and water polo players (67%) and artistic swimmers (61%) having the highest infection rates... {Marg: maybe group swim lessons aren't as benign as I thought? I worried more about dressing rooms...}

The majority reported mild (51%) or moderate (27%) symptoms, while 16% remained asymptomatic.

Reinfection occurred in 13%... 92% of athletes received at least two vaccine doses

...10% of initial infections led to long COVID, with fatigue (65%) and shortness of breath (48%) being the most common long-term symptoms...

...In conclusion, most athletes experienced a benign disease course despite a relatively high infection rate. {Marg: but 10% experienced LC, which may have ended/paused some people's athletic careers / scholarships?}
-----------------------------------------------

Vencel Juhász et al. 2023. Retrospective study of COVID-19 experiences in elite multinational aquatic athletes. Nature Scientific Reports volume 13, Article number: 13978 (26 Aug 2023) https://www.nature.com/articles/s41598-023-40821-2

Dillon S. McBride et al. 2023. Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer. Nature Communications volume 14, Article number: 5105 (28 Aug 2023) https://www.nature.com/articles/s41467-023-40706-y

Abstract
The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2–8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock.

...Discussion
...SARS-CoV-2 is currently not considered an important risk for North American livestock, but the continued spread of the virus in WTD, humans, and other hosts could open new pathways for SARS-CoV-2 evolution.

Some seniors infected with Omicron variants were more susceptible to reinfection, not less: McMaster study
Kenyon Wallace | August 21, 2023

A surprising finding by researchers at McMaster University runs counter to prevailing wisdom that previous COVID infection protects against future infections.

...In a sign that scientists still don’t fully understand how some COVID-19 variants manage to evade the immune system, a new Ontario study has found that retirement- and long-term-care home residents infected during the first Omicron wave were 20 times more likely to get reinfected by the virus than those who avoided a prior infection.

The surprising finding by researchers at McMaster University runs counter to the prevailing wisdom that a previous COVID infection affords protection against future infections, at least in the older adults who participated in the study.

“This is important because our vaccine strategy is based on the assumption that once you’ve had an infection, you’re going to be a little bit more protected so you don’t need to get vaccinated right away,” said Dawn Bowdish, an immunologist at McMaster University and a co-author of the study ... “We found that in older people at least, for some of the variants, the opposite seems to be true. Instead of becoming less vulnerable, they become more vulnerable to infection.”...

https://www.thestar.com/news/canada/some-seniors-infected-with-omicron-variants-...
--------------------------------------------------

Dawn Bowdish @MsMacrophage | 12:08 PM · Aug 25, 2023:
Executive Director, Firestone Institute for Respiratory Health. Canada Research Chair in Aging and Immunity

Addendum: To address some of your questions-
1)*all* participants in the study were vaccinated,
2) the average time btw their BA1/2 and BA5 infection was 4-5 months (the observation period is the start of the BA.5 wave, not right after their first infection).
--------------------------------------------------

Jessica A. Breznik et al. 2023. Early Omicron infection is associated with increased reinfection risk in older adults in long-term care and retirement facilities. (The Lancet Discovery Science) eCinicalMedicine., 21 August 2023. DOI:https://doi.org/10.1016/j.eclinm.2023.102148 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00325-5/fullt...

Summary
...Findings. 133 of 750 participants (17.7%) had a PCR-confirmed Omicron infection during the observation period {April 1 to June 30, 2022}. Increased infection risk was associated with prior Omicron infection (at 9–29 days: 47.67 ...), and this was not attributed to days since fourth vaccination (1.00 ...) or residence outbreaks (more than 6 compared to 6 or fewer...0.95 ...). Instead, reinfected participants had lower serum neutralizing antibodies to ancestral and Omicron BA.1 SARS-CoV-2, and lower anti-RBD IgG and IgA antibodies, after their initial Omicron infection.

Interpretation. Counterintuitively, SARS-CoV-2 Omicron infection was associated with increased risk of Omicron reinfection in residents of long-term care and retirement homes. Less robust humoral hybrid immune responses in older adults may contribute to risk of Omicron reinfection.

Maxime Taquet et al. 2022. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. The Lancet Psychiatry, August 17, 2022. DOI:https://doi.org/10.1016/S2215-0366(22)00260-7

Abstract
...Findings. ... Risks of the common psychiatric disorders returned to baseline after 1–2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days). By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period.

Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02...) or anxiety (1·00...) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 ... to 2·16 ...). Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days).

A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures. Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort). Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate. With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.

Interpretation. This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.

Effect of smoking and nicotine in SARS-CoV-2 infection?

Zahra Salehi et al. 2023. The controversial effect of smoking and nicotine in SARS-CoV-2 infection. (BMC) Allergy, Asthma & Clinical Immunology volume 19, Article number: 49 (1 June 2023) https://aacijournal.biomedcentral.com/articles/10.1186/s13223-023-00797-0

Abstract
The effects of nicotine and cigarette smoke in many diseases, notably COVID-19 infection, are being debated more frequently. The current basic data for COVID-19 is increasing and indicating the higher risk of COVID-19 infections in smokers due to the overexpression of corresponding host receptors to viral entry. However, current multi-national epidemiological reports indicate a lower incidence of COVID-19 disease in smokers. Current data indicates that smokers are more susceptible to some diseases and more protective of some other. Interestingly, nicotine is also reported to play a dual role, being both inflammatory and anti-inflammatory. In the present study, we tried to investigate the effect of pure nicotine on various cells involved in COVID-19 infection. We followed an organ-based systematic approach to decipher the effect of nicotine in damaged organs corresponding to COVID-19 pathogenesis (12 related diseases). Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.

Science Magazine @ScienceMagazine | 11:00 AM · Sep 6, 2023:
An inhalable formulation of an ACE2 decoy neutralizes multiple #Omicron subvariants and protects animals from infection with the Delta variant, potentially offering a non-invasive therapy for current and emerging #SARSCoV2 variants.

Emiko Urano et a. 2023. An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.
Science Translational Medicine, 30 Aug 2023, Vol 15, Issue 711. DOI: 10.1126/scitranslmed.adi2623 https://www.science.org/doi/10.1126/scitranslmed.adi2623

Editor’s summary
Although SARS-CoV-2 infects through the respiratory tract, the therapeutics that have been developed so far are rarely delivered in the same manner. Here, Urano et al. aimed to change this by delivering a previously developed, engineered angiotensin-converting enzyme 2 (ACE2) decoy by inhalation delivery. The ACE2 decoy, which the authors demonstrated is resistant to SARS-CoV-2 escape mutants, conferred protection against disease in mice, hamsters, and non-human primates when delivered through inhalation. These results support further clinical development of ACE2 decoy molecules and suggests that they could be delivered directly to the respiratory tract as a therapeutic. —Courtney Malo

Common-cold coronavirus* imprinting is associated with postacute sequelae of COVID-19 {Long COVID} in patients with systemic autoimmune rheumatic diseases.

Jonathan D. Herman et al. 2023. Why do some individuals develop post-acute sequelae of COVID-19 (PASC) while others do not? Science Translational Medicine 6 Sep 2023, Vol 15, Issue 712. DOI: 10.1126/scitranslmed.adf6598

Editor’s summary
It is not clear why some individuals develop postacute sequelae of COVID-19 Long COVID (PASC) while others do not. Here, Herman et al. used systems serology to probe antibody features associated with development of PASC in individuals with rheumatic diseases. The authors found that the presence of functional antibodies specific to OC43,* an endemic human coronavirus, were enriched in PASC. Although more causal analysis is warranted, these results suggest that immunological imprinting specific to OC43* may be a driver of PASC, particularly in individuals with prior rheumatic disease.

* "Common human coronaviruses, including types ... OC43 ... usually cause mild to moderate upper-respiratory tract illnesses, like the common cold. Most people get infected with one or more of these viruses at some point in their lives. https://www.cdc.gov/coronavirus/general-information.html

Eric Topol {Scripps} @EricTopol | 6:56 PM · Sep 8, 2023:
Take note: JP's model based on US wastewater indicates the current wave for infections is approaching the level of the ancestral, Alpha and Delta waves

Quote
JWeiland @JPWeiland | 6:40 PM · Sep 8, 2023
Scientist. Infectious disease modeler.

September 8th US update:
Community spread of Covid is "high", with a correction upwards last week as well. Current estimates:
🔸720,000 new infections/day
🔸1 in every 460 new people were infected today
🔸1 in every 46 people currently infected
Graph ( https://twitter.com/JPWeiland/status/1700277959532196168/photo/1 )

Richard Corsi, PhD, PE (Texas) @CorsIAQ | 9:07 PM · Sep 9, 2023
Dean of Engineering, University of California, Davis Indoor Environmental Engineer Proud UC Davis Alumnus

10h • 19 tweets • 3 min read Twitter logo Read on Twitter
1/ Been hearing of some push back by school districts over fears that fan motors on CR-Boxes may overheat and be a fire hazard. This thread addresses those concerns...

https://twitter.com/CorsIAQ/status/1700677380795515067
https://threadreaderapp.com/thread/1700677380795515067.html

Unraveling long COVID: Here's what scientists who study the illness want to find out
Will Stone | September 9, 2023

... researchers are making progress in the field, and they presented their recent findings at one of the first major gatherings dedicated to sharing emerging evidence about the possible root cause of long COVID and implications for treatment.

Honing in on some key suspects behind the disease
Finding activated T cells where they shouldn't be
Microclots could point the way to treatment
Sex differences may play a role in long COVID risk
Viral persistence offers one possible target for treating long COVID

https://www.npr.org/sections/health-shots/2023/09/09/1198342040/long-covid-cause...

Children aged 4 months to 2 years are more likely to have antibodies that attack insulin producing cells (a feature of type 1 diabetes) if they have had COVID.

Marija Lugar et al. 2023. SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood. JAMA. Published online September 8, 2023. doi:10.1001/jama.2023.16348 https://jamanetwork.com/journals/jama/fullarticle/2809621

Key Points
... Findings In this longitudinal cohort study of 885 infants with an elevated genetic risk of type 1 diabetes, the incidence rate of islet autoantibodies developing concurrently with or soon after SARS-CoV-2 antibodies were detected was 7.8 per 100 person-years and was 3.5 per 100 person-years in children without SARS-CoV-2 antibodies, a significant difference.

Meaning In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.

COVID levels are so high, they’re hovering near 2020’s initial peak, as the WHO urges those at high risk to take any booster they can get their hands on
Erin Prater | September 16, 2023

https://fortune.com/well/2023/09/16/united-states-covid-levels-approach-first-pa...

New weekly Covid admissions per 100,000 as of 9 Sept 2023, by state:
https://twitter.com/DrEricDing/status/1704137842841067689/photo/1

Lucky me, a collection of aches and pains that I ascribed to LC virtually disappeared after MY first vaxx...

COVID vaccination after long COVID may be linked to better outcomes (News brief)
Stephanie Soucheray | September 18, 2023

A new observational study from Canadian researchers reveals that COVID vaccination after long COVID was tied to fewer symptoms, increased well-being, and less inflammation...February 12 to September 8, 2021...Montreal...

...The five most common PCC (post-COVID condition) symptoms reported at the beginning of the study were fatigue (81.9%), trouble with concentration (47.0%), trouble with memory (39.8%), headache (32.5%) and shortness of breath at rest (31.3%) during all follow-ups.

After vaccination, 77.8%, 7.4%, and 14.8% of participants reported improved, worsened and unchanged well-being scores, respectively, the authors said. And 86%, 8.3% and 5.6% of participants reported fewer, more, and the same number of PCC symptoms, respectively.

...Sixteen cytokines and chemokines were significantly decreased after vaccination in participant blood samples, a sign that inflammatory proteins were mitigated by vaccination...

https://www.cidrap.umn.edu/covid-19/covid-vaccination-after-long-covid-may-be-li...
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Maryam Nayyerabadi et al. 2023. Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses. Intl J of Infectious Diseases. Open Access. Published:September 15, 2023 DOI:https://doi.org/10.1016/j.ijid.2023.09.006 https://www.ijidonline.com/article/S1201-9712(23)00720-8/fulltext

Highlights
• COVID-19 vaccination post-PCC reduced number of symptoms and increased well-being
• COVID-19 vaccination post-PCC down-regulated systemic markers of inflammation
• COVID-19 vaccination post-PCC did not abrogate the persistence of viral products
• A viral reservoir not cleared by one or two vaccine doses may persist

Does the risk of getting long Covid increase each time you get reinfected?
Elizabeth Cooney | Sept. 20, 2023
https://www.statnews.com/2023/09/20/do-long-covid-odds-increase-with-second-infe...

Olga Blagova et al. 2023. Chronic biopsy proven post-COVID myoendocarditis with SARS-Cov-2 persistence and high level of antiheart antibodies. Clinical Cardiology. First published: 19 July 2022. https://doi.org/10.1002/clc.23886 https://onlinelibrary.wiley.com/doi/10.1002/clc.23886

Abstract
...Methods...Fourteen patients (nine male...) ...The average time of admission after COVID-19 was 5.5 ... months. ...Coronary atherosclerosis was ruled out in all patients over 40 years.

Results
The new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID-19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28%.... Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS-Cov-2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47%...

Conclusions
COVID-19 can lead to long-term severe post-COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post-COVID myoendocarditis.

Eric Topol {Scripps} @EricTopol | 6:45 PM · Sep 20, 2023
Doctors with #LongCovid...
~4% of UK healthcare workers
"These are doctors left at risk and let down during the pandemic, and they're still being let down with lack of support."
"We've been left to rot."

Highlighted text:
https://twitter.com/EricTopol/status/1704627862731714800/photo/1
https://twitter.com/EricTopol/status/1704627862731714800/photo/2
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Adele Waters 2023. Long covid: the doctors’ lives destroyed by an illness they caught while doing their jobs. BMJ 20 Sept 2023;382:p1983. doi: https://doi.org/10.1136/bmj.p1983 https://bmj.com/content/382/bmj.p1983

>44 margd: >46 jjwilson61:

Covid Drug Paxlovid Now Less Effective Than In Early Trials—But It’s Still Great At Preventing Death
William Skipworth | 21 Sept 2023

Paxlovid—Pfizer’s antiviral Covid-19 treatment—is 37% effective at preventing hospitalization or death in high-risk patients compared with no treatment, according to a study published Thursday in the JAMA Network Open*, well below the 88% effectiveness rate Pfizer and regulators reported in clinical trials in 2021—though it remains very effective at staving off death.

The study found that when excluding hospitalizations and looking at death alone, the drug is 84% effective.

The observational study analyzed electronic health records from thousands of patients at the Cleveland Clinic Health System in 2022 and early 2023 to determine Paxlovid’s effectiveness, using real-world data rather than the clinical trials that were used before.

The study also found another antiviral Covid-19 treatment, Merck’s Lagevrio, was 42% effective in preventing hospitalization or death and 77% effective against death alone.

...Crucial Quote
Paxlovid is still “definitely recommended for high-risk patients,” said University of North Carolina professor Danyu Lin, one of the study’s authors, according to Bloomberg...

https://www.forbes.com/sites/willskipworth/2023/09/21/covid-drug-paxlovid-now-le...
-------------------------------------------------------

* Dan-Yu Lin et al. 2023. Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections.
JAMA Netw Open. 21 Sept 2023;6(9):e2335077. doi:10.1001/jamanetworkopen.2023.35077 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809779

"Compared with controls, {Long Covid} patients were more likely to have MRI evidence of lung abnormalities..., brain abnormalities..., and kidney abnormalities ... , whereas cardiac and liver MRI abnormalities were similar between patients and controls..."

Long COVID can cause long-term damage to multiple organs, study finds
Josephine Franks | 23 September 2023

Scans of long COVID patients show a third have multiple organ injuries months after leaving hospital, a new study shows...

https://news.sky.com/story/long-covid-can-cause-long-term-damage-to-multiple-org...
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The C-MORE/PHOSP-COVID Collaborative Group 2023. Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study. The Lancet Respiratory Medicine. Open Access. Published:September 22, 2023 DOI:https://doi.org/10.1016/S2213-2600(23)00262-X https:..//www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00262-X/fulltext#%20

ABSTRACT
...Findings. Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years...; 158 (61%) male and 101 (39%) female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years...; 30 (58%) male and 22 (42%) female) were included in the analysis. Patients were assessed at a median of 5·0 months ... after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 (61%) of 259 vs 14 (27%) of 52...) and independently associated with COVID-19 status (odds ratio OR 2·9 ...) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (... parenchymal abnormalities), brain abnormalities (... more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities ... lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years ... mean age of 59·8 years...with multiorgan abnormalities vs mean age of 52·8 years... without multiorgan abnormalities; ...), more likely to have three or more comorbidities (OR 2·47 ...), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 ...) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.

Interpretation.
After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.

Fig 3 Venn diagram showing overlap of organ abnormalities
https://twitter.com/EricTopol/status/1705385632712020313/photo/1

Dr. Sean Mullen @drseanmullen | 12:36 PM · Sep 24, 2023:
Research Director @EtcLab studying #Exercise #Technology #Cognition #Neuroscience
https://twitter.com/drseanmullen/status/1705984663733289216

As a PhD in Education with expertise in health behavior adherence, health tech and cognitive science, I believe there are multiple, co-contributing factors in the US and abroad {re: Why do you... think so many healthcare facilities, MD & dental offices, etc are not masking?}:

1. People can’t stick to things, period. Research on any heath behavior and it’s 50+% stop within 3-6 months. People can’t even take their BP meds regularly after a ❤️ attack!!

2. Survivor bias & other logical fallacies. Everyone knows people who’ve been infected 1+ times (most of the living had the experience). Survivors had “mild symptoms.” Must not be that bad right? It’s just “other people” (with XYZ) who are “vulnerable.”

3. Mainstream Media Silence & Propagation of Misinformation. It impacts culture. If people aren’t talking about it on TV, why would they discuss while on break? Then media picks up on a controversial study like the Cochrane review that no one interpreted correctly (and the hidden agenda). Note that no one is talking about the recent RCT showing efficacy of masking or the horrifying data showing neural cell fusion or autoimmune effects (just two examples).

4. Why would the average clinician stay on top of scientific papers (especially when it’s not covered in media or is downplayed by “experts”)? They didn’t pre-pandemic, why would they now?

5. Normative Peer Pressure. Nearly everyone succumbs to the majority of peers.

6. Low Relevant Health Literacy (Ignorance). There aren’t really any experts on this virus. It’s novel. It keeps evolving. You’d be surprised how little medical trainees learn about areas outside their specialty area but they certainly aren’t trained in all the areas you need to keep up with this.

I could keep going but there are layers to this disaster onion…
--------------------------------------------

{What explains the flaming hatred of masks, though?}
SM: Ok, a couple more…
- Perceived inability to breathe
- Perception that one cannot communicate with something on their mouth
- Perception that masking is only to appease others & that it is ineffective
- Ego/ vanity

Just another mom @erinelmvale
I’d like to add, that the time lapse from going to a super spreader event, or even the grocery store unmasked and the start of symptoms also has a huge part to play. If someone walked out of the large indoor festival and got hit by that covid lightening bolt right away…..

SM: Capacity to continue making those choices (no matter how small you may perceive them to be), is malleable and susceptible to… stress, being sick, health illiteracy and ability to resist misinformation and keep up with latest scientific developments). It’s a skill many don’t have. Pre-pandemic, just ~20% of adults maintained physical levels consistent with public health guidelines. Roughly 2/3 of fitness club members stop going within the first 1-3 months. Sure it’s a choice. Just like not drinking alcohol. Most can’t enact health decisions or inhibit unhealthy ones when needed.
________________________________________________

Normalcy bias, or normality bias, is a cognitive bias which leads people to disbelieve or minimize threat warnings. Consequently, individuals underestimate the likelihood of a disaster, when it might affect them, and its potential adverse effects. (Wikipedia)

Important advance in diagnosing Long COVID. Important for treatment, insurance, etc.
May help with other postviral disease conditions, e.g., EBV, Lyme, etc.?

Prof. Akiko Iwasaki {Yale U} @VirusesImmunity | 11:40 AM · Sep 25, 2023:

So pleased to report that our Mount Sinai-Yale long COVID (MY-LC) paper with @putrinolab & others is now published!! Proud of the hard work of all who contributed. We found biological signatures that can distinguish people with vs. without #longCOVID (1/)

...What biological factors did we find? Key findings = people with long COVID had 1) lower circulating cortisol, 2) higher activated B and cytokine-secreting T cells, 3) higher anti-Spike IgG, 4) higher EBV reactive Abs. No significant differences in # of autoantibodies. (5/)
https://twitter.com/VirusesImmunity/status/1706332982309491187/photo/1

Machine learning identified key immune factors that can distinguish those with long COVID. These factors included lower levels of cortisol, conventional DC1, central memory T and higher levels of EBV IgG, galectin-1, APRIL...etc. (6/)
https://twitter.com/VirusesImmunity/status/1706332987661451417/photo/1

What does this mean? The study is exploratory and signal seeking, not hypothesis testing. It is a first step in identifying biomarkers that can be used in the future to diagnose long COVID. To get there, we still need to validate these markers in external cohorts. (7/)...
-----------------------------------------------------

Jon Klein et al. Akiko Iwasaki 2023. Distinguishing features of Long COVID identified through immune profiling. Nature (25 Sept 2023) https://www.nature.com/articles/s41586-023-06651-y

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract
Post-acute infection syndromes (PAIS) may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a PAIS known as “Long COVID” (LC). Individuals with LC frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions...; however, the biological processes associated with the development and persistence of these symptoms are unclear. Here, 273 individuals with or without LC were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC. Marked differences were noted in circulating myeloid and lymphocyte populations relative to matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with LC. Further, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with LC, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with LC. Integration of immune phenotyping data into unbiased machine learning models identified key features most strongly associated with LC status. Collectively, these findings may help guide future studies into the pathobiology of LC and aid in developing relevant biomarkers.
__________________________________________

Eric Topol @EricTopol | 11:22 AM · Sep 25, 2023:
At the time this paper was preprint posted, I put together this explainer to highlights its importance

Some Light on Long Covid
A cluster of new data
Eric Topol | Aug 11, 2022
https://erictopol.substack.com/p/some-light-on-long-covid
__________________________________________

https://www.nbcnews.com/health/health-news/long-covid-differences-blood-test-stu...
__________________________________________
ETA

Long COVID Blood Tests Show Distinct Immune and Hormone Function
— Algorithm may help predict who gets long COVID
Judy George | September 25, 2023

...An algorithm that incorporated blood test and self-reported survey data showed diagnostic potential with an area under the curve (AUC) of 0.94, Iwasaki and co-authors found.

"We found a number of immunological and hormonal factors that collectively are able to distinguish people with versus without long COVID at 94% accuracy," Iwasaki told MedPage Today. "This study speaks to the underlying biological causes of long COVID and provides a basis for future studies that interrogate various therapies that target the root causes of this disease."

"The reduced cortisol levels found in the long COVID patients suggest hypothalamus-pituitary-adrenal imbalance," she pointed out. "The elevated activated B cells and exhausted T cells suggest persistent antigen and potentially persistent virus infection. The EBV reactivation, which was demonstrated by others also, inform about a subset of patients who may benefit from EBV-targeting therapies."

This work is "a crucial first step towards identifying a set of biological differences between people with and without long COVID" and may lead to novel blood biomarkers for an objective diagnosis of long COVID, co-author David Putrino, PhD, of Icahn Mount Sinai in New York City, told MedPage Today...

The study "provides physicians with important insights by highlighting the fact that people with long COVID show measurable signs of hormonal and immunological dysfunction, which should serve as further irrefutable evidence that long COVID is not a functional or psychosomatic diagnosis," Putrino said...

https://www.medpagetoday.com/neurology/longcovid/106485

US-resident volunteers sought for Scripps study:

Eric Topol @EricTopol | 3:13 PM · Sep 25, 2023:
physician-scientist, author, editor http://drerictopol.com Ground Truths: http://erictopol.substack.com

If you are immunocompromised or age 65+, please consider joining our study that provides free molecular Covid tests, telemedicine, and rapid Paxlovid home delivery. ⁦@ScrippsRTI ⁩ ⁦@scrippsresearch ⁩ ⁦@CueHealth ⁩ ⁦@julialmv ⁩

The ImmunoCARE Study
Rapid, Accurate COVID Testing to Reduce Hospitalization of Immunocompromised Individuals
https://immunocare.scripps.edu/

Vincent Zhang et al. 2023. Incidence of New-Onset Hypertension Post–COVID-19: Comparison With Influenza. (AHA)
Hypertension. 21 Aug 2023;80:2135–2148 https://doi.org/10.1161/HYPERTENSIONAHA.123.21174 https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.123.21174

Abstract
...RESULTS: At 6-month follow-up, new-onset persistent hypertension was seen in 20.6% of hospitalized patients with COVID-19 and 10.85% of nonhospitalized patients with COVID-19. Persistent hypertension incidence among hospitalized patients did not vary across the pandemic, whereas that of hospitalized patients decreased from 20% in March 2020 to ≈10% in October 2020 ... and then plateaued thereafter. Hospitalized patients with COVID-19 were 2.23 ... times and nonhospitalized patients with COVID-19 were 1.52 ... times more likely to develop persistent hypertension than influenza counterparts. Persistent hypertension was more common among older adults, males, Black, patients with preexisting comorbidities (chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease), and those who were treated with pressor and corticosteroid medications. Mathematical models predicted persistent hypertension with 79% to 86% accuracy. In addition, 21.0% of hospitalized patients with COVID-19 with no prior hypertension developed hypertension during COVID-19 hospitalization.

CONCLUSIONS: Incidence of new-onset persistent hypertension in patients with COVID-19 is higher than those with influenza, likely constituting a major health burden given the sheer number of patients with COVID-19. Screening at-risk patients for hypertension following COVID-19 illness may be warranted.

Michael Mina {formerly Harvard} @michaelmina_lab | 1:47 AM · Sep 26, 2023

Now that the GOV is again giving out free rapid tests (http://covidtests.gov)
If you do turn Positive this fall/winter, your rapid test may tell you more about your status (at the time of testing) than you think!
How much time X how dark it gets

Here's how I think about it:
https://twitter.com/michaelmina_lab/status/1706545922857992354/photo/1

Harry Spoelstra @HarrySpoelstra | 2:58 AM · Sep 26, 2023:
CardioVascular Surgeon, international clinical research

Tonsils are major sites of persistence of SARS-CoV-2 in children

❗Hallo, your attention, Children/SarsCoV2/Tonsils

➡️"Study shows that #SARSCoV2 of different lineages can infect tonsils and adenoids in one quarter of children undergoing tonsillectomy"

➡️"Showing that tonsils may be sites of prolonged infection, even without evidence of recent COVID-19 symptoms"

➡️"SARS-CoV-2 infection of B and T lymphocytes, macrophages, and dendritic cells may interfere with the mounting of immune responses in these secondary lymphoid organs"

➡️Unknown potential immunoinflammatory consequences"

➡️"These findings underpin the potential role of hypertrophic tonsils as sites of SARS-CoV-2 infection in children, for an undetermined prolonged time"

➡️"Such smoldering SARS-CoV-2 infection might involve continuous low-level production of viral proteins and cell-to-cell transmission, which circumvent immune surveillance and subvert sterilizing immunity by low virus replication and possibly antigenic variation"

➡️"Shedding of SARS-CoV-2 RNA in respiratory secretions from silently infected children raises concern about possible diagnostic confusion in the presence of symptoms of acute respiratory infections caused by other etiologies"

Histology, graphs ( https://twitter.com/HarrySpoelstra/status/1706563877285032429/photo/1 )
--------------------------------------------------

Thais Melquiades de Lima et al. 2023. Tonsils are major sites of persistence of SARS-CoV-2 in children. Clinical Microbiology. 22 September 2023. DOI: https://doi.org/10.1128/spectrum.01347-23 https://journals.asm.org/doi/10.1128/spectrum.01347-23 https://journals.asm.org/doi/10.1128/spectrum.01347-23

...Importance. This study shows that SRS-CoV-2 of different lineages can infect tonsils and adenoids in one quarter of children undergoing tonsillectomy. These findings bring advancement to the area of SARS-CoV-2 pathogenesis, by showing that tonsils may be sites of prolonged infection, even without evidence of recent COVID-19 symptoms. SARS-CoV-2 infection of B and T lymphocytes, macrophages, and dendritic cells may interfere with the mounting of immune responses in these secondary lymphoid organs. Moreover, the shedding of SARS-CoV-2 RNA in respiratory secretions from silently infected children raises concern about possible diagnostic confusion in the presence of symptoms of acute respiratory infections caused by other etiologies....

Anna Coleman et al. 2023. A deep dive into selected work sectors during the COVID-19 pandemic and the “living with COVID” phase: understanding similarities and differences in practice, perceptions, and preparedness. Annals of Work Exposures and Health, 23 September 2023. https://doi.org/10.1093/annweh/wxad053 https://academic.oup.com/annweh/advance-article/doi/10.1093/annweh/wxad053/72815...

{UK}

...Discussion
...Throughout both phases of this PROTECT research study {1. sector-specific empirical research conducted between October 2020 and February 2022...to explore the extent of similarities and differences in sector-specific research findings. , 2. “living with COVID” since February 2022}, the majority of participants expressed difficulty in responding to the changing rules and regulations issued by UK Government. Organisations with nationwide operations also struggled to bridge the gap between differing guidance across 4 UK nations in some sectors (construction, logistics/delivery, and public transport). The burden and cost for sectors responding to changing guidance was commonly acknowledged as a challenge, heightened by external factors (e.g. cost of living crisis, Ukraine war, etc.), unrelated to COVID-19, demanding attention and resource. Furthermore, a lack of understanding amongst workers and the public of why the rules, and changes to these rules over time, were necessary often compounded these issues. In this regard compliance fatigue, the reduction of enforcement powers and loss of data sources through which to actively monitor COVID-19 were said, during Phase 2, to make it more challenging for organisations to apply and enforce mitigation measures during the “living with COVID” phase.

Another common thread to emerge from both Phases of the research was a wish to understand which mitigations worked best, in what contexts and their relative cost effectiveness. During the “living with COVID” phase {2}, experts and organisational leaders remained unsure about which measures were the most impactful for their organisations, workers, and service users. This was due to the introduction of multiple measures simultaneously, likely compounded by the diverse challenges to mitigating the risk of SARS-COV-2 transmission evident in different sectors, sub-sectors, organisations, or even workplace settings. Indeed, layering control strategies in any given context was cited by some as an effective strategic approach (Canham et al. 2023).

Participant’s views and organisational practices changed quickly during the different phases of the pandemic. Following removal of the majority of restrictions, most sectors/organisations were keen to restore normal practice, thereby treating COVID-19 like any other illness, while planning for future stability and preparing for future health emergencies.

It is essential that those making policy at the national level and decision makers in organisations are mindful of the lessons learned and knowledge gained at all levels (national, regional, local, organisational, and individual) during the COVID-19 pandemic. Therefore, recommendations are proposed for: managing ongoing recovery, as sectors/organisations continue “living with COVID” and other respiratory diseases (e.g. seasonal flu); balanced with longer-term planning for the next public health crisis (discussed below)...

Fig 1 Timeline of COVID-19 Government policy and decision making in England. ( https://academic.oup.com/view-large/figure/418714134/wxad053_fig1.jpg )

Table 2. Mitigations by sector. ( https://academic.oup.com/view-large/418714157 )

Fig 2 ( https://academic.oup.com/view-large/figure/418714203/wxad053_fig2.jpg )

Preventing Aerosol-Transmissible Diseases in Healthcare Settings: The Need for Protective Guidelines and Standards
Rutgers School of Public Health
Webinar
FRIDAY, OCTOBER 13, 12:00 - 3:00 PM EST
Register at: go.rutgers.edu/PreventATD

...This webinar will include a scientific review of significant gaps in HICPAC’s {CDC's Healthcare Infection Control and Prevention Advisory Committee} proposed revisions to the {CDC} guidelines. Speakers will review the science that HICPAC and CDC should be considering for preventing transmission of aerosol transmissible diseases. Testimony on the importance of effective infection control measures will be provided by front line healthcare workers and patients. A list of recommended revisions will be produced that will be submitted to the CDC.

https://rutgerstraining.sph.rutgers.edu/PreventATD/

Magen E. Francis et al. 2023. Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2. Nature Communications volume 14, Article number: 5990 (26 Sept 2023) https://www.nature.com/articles/s41467-023-41761-1

...Discussion...results are important for calculating the antigenic distance and immune recall dynamics between coronaviruses to determine mechanisms of cross-protection. Understanding the immunological interactions between different but related viral antigen combinations will be useful for designing pan-coronavirus vaccines and avoiding OAS*...

*Immunological imprinting, previously described as ‘Original Antigenic Sin’ or OAS, is the powerful mark, positive or negative, that a first viral infection makes on the host’s immune system and the resulting response to subsequent antigenically related but distinct viral exposures.

Just wanted to comment that I appreciate your posts!

Thank you--like a detective story, isn't it? False leads, sudden breakthroughs, paradigm shifts, ever-evolving understanding... And then there's the socio-economic piece...

Me too.

Medicare sent an email yesterday announcing that the new booster version is now available.

T. Ryan Gregory @TRyanGregory | 8:05 AM · Sep 30, 2023:
Evolutionary biologist. {U Guelph}

It hasn't been "one variant, one tsunami" for more than a year, it's been about how high the baseline is kept by the evolving variant soup. This paper looks at how variants and our efforts at mitigation will affect how much COVID we have to deal with...
------------------------------------------------------

Sarah Otto @sarperotto | 7:53 AM · Sep 30, 2023:
Evolutionary biologist; Prof at UBC

Variant after variant of SARS-CoV-2 has spread over the past year. But what does that mean for the long-term burden of COVID-19? Check out our new preprint {link below}

➡️We find that the long-term rise in cases is not well predicted by rate of spread of a variant. Even with the same selection "s", case #s rise least if the variant is transiently immune evasive, most if persistently immune evasive, & in between for more transmissible variants.
Graphs ( https://twitter.com/sarperotto/status/1708087672592273516/photo/1 )

➡️This finding highlights the need to study when and how variant-specific immune responses develop. Which variants are prone to elicit antibodies that recognize them in subsequent infections and which don't?

➡️We can balance the rise in cases due to variants through vaccination and protective measures, such as ventilation & masking indoors. These always reduce an individual's risk of infection, cutting down # of infections per year. {Check out report: https://royalsociety.org/topics-policy/projects/impact-non-pharmaceutical-interv... }

➡️Protective measures, such as improved ventilation and masking indoors, provide double protection to those around you, reducing the chance that you get infected in the first place and that you then infect your friends, family, and other contacts.💉🪭😷

➡️If uptake of 💉🪭😷 is high enough, we can drive down and keep down the number of cases of COVID-19, as well as reduce long-COVID and severe COVID risks. For example, we can tamp out ~42% of cases if ~2/3 of us are boosted annually.
Graph ( https://twitter.com/sarperotto/status/1708087682864226595/photo/1 )

➡️Even though COVID-19 is endemic & continues to evolve, that does not mean it is out of our control. Get a booster when available, mask in indoor crowded spaces, & invest in air filtration & ventilation to protect all. We find that benefits ⬆️ with more uptake of more measures.
----------------------------------------------------------

Sarah Otto et al. 2023. Endemic means change as SARS-CoV-2 evolves. MedRx 29 Sept 2023
doi: https://doi.org/10.1101/2023.09.28.23296264
This article is a preprint and has not been certified by peer review

Abstract
COVID-19 has become endemic, with dynamics that reflect the waning of immunity and re-exposure, by contrast to the epidemic phase driven by exposure in immunologically naive populations. Endemic does not, however, mean constant. Further evolution of SARS-CoV-2, as well as changes in behaviour and public health policy, continue to play a major role in the endemic load of disease and mortality. In this paper, we analyse evolutionary models to explore the impact that newly arising variants can have on the short-term and longer-term endemic load, characterizing how these impacts depend on the transmission and immunological properties of variants. We describe how evolutionary changes in the virus will increase the endemic load most for persistently immune-escape variants, by an intermediate amount for more transmissible variants, and least for transiently immune-escape variants. Balancing the tendency for evolution to favour variants that increase the endemic load, we explore the impact of vaccination strategies and non-pharmaceutical interventions (NPIs) that can counter these increases in the impact of disease. We end with some open questions about the future of COVID-19 as an endemic disease.

Study: 75% of infants hospitalized with COVID-19 born to unvaccinated women
Stephanie Soucheray | September 28, 2023

...evidence from the Omicron surge shows {mRNA vaccines given to pregnant women} were effective in preventing hospitalizations for infants ages 6 months or less. Currently, babies 6 months and older can get vaccinated...

VE {vaccine effectiveness} of 54% for babies under 3 months
Only 54.7% of HCPs {healthcare providers} offered vaccines to women

https://www.cidrap.umn.edu/covid-19/study-75-infants-hospitalized-covid-19-born-...
---------------------------------------------------

Simeone RM, Zambrano LD, Halasa NB, et al. Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19–Associated Hospitalizations in Infants Aged less than 6 Months During SARS-CoV-2 Omicron Predominance — 20 States, March 9, 2022–May 31, 2023. {CDC} MMWR Morb Mortal Wkly Rep 2023;72:1057–1064. DOI: http://dx.doi.org/10.15585/mmwr.mm7239a3

Meghani M, Salvesen Von Essen B, Zapata LB, et al. COVID-19 Vaccination Recommendations and Practices for Women of Reproductive Age by Health Care Providers — Fall DocStyles Survey, United States, 2022. MMWR Morb Mortal Wkly Rep 2023;72:1045–1051. {CDC} DOI: http://dx.doi.org/10.15585/mmwr.mm7239a1

Razzaghi H, Kahn KE, Calhoun K, et al. Influenza, Tdap, and COVID-19 Vaccination Coverage and Hesitancy Among Pregnant Women — United States, April 2023. {CDC} MMWR Morb Mortal Wkly Rep 2023;72:1065–1071. DOI: http://dx.doi.org/10.15585/mmwr.mm7239a4

Isaac Bogoch (U Toronto) @BogochIsaac | 9:51 AM · Sep 30, 2023

Large UK investigation into the cases of acute pediatric hepatitis of unknown origin:
"We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis."
--------------------------------------------------------

Sema Mandal et al. 2023. Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK. The Lancet Child and Adolescent Health. Open Access Published:September 26, 2023 DOI:https://doi.org/10.1016/S2352-4642(23)00215-8 https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(23)00215-8/fullt...

Summary...We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation.
______________________________________________

Yisu Liu et al. 2023. T Cell Cross-reactivity in Autoimmune-like Hepatis (Letter). hLife Available online 28 September 2023. In Press, Journal Pre-proof. https://doi.org/10.1016/j.hlife.2023.09.002. https://www.sciencedirect.com/science/article/pii/S2949928323000093

...we hypothesized that following SARS-CoV-2 infection or vaccination, T cells carrying TCRs (T cell receptors) that recognize self-antigens undergo clonal expansion, which could eventually result in the onset of autoimmune-like hepatitis

...In conclusion, our findings support the notion that cross-reactivity of clonally expanded T cells could be one of the causes of COVID-19-related autoimmune-like hepatitis, including pediatric hepatitis of unknown etiology.

Some think Omicron is so different from Wuhan Wild Type that it's like a new species...below is technical discussion of Omicron biology:

Jeff Gilchrist @jeffgilchrist | 8:28 AM · Oct 1, 2023:
Senior AI Data Scientist at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute collaborating with physicians, researchers, and other teams on the use of machine learning.

Very interesting biology thread about the differences of why Omicron variants have a harder time infecting lung cells vs upper airways but still replicate really well in the gut. Definitely worth the read to the end. ...

Quote
Ryan Hisner @LongDesertTrain | 10:02 PM · Sep 30, 2023:
Teacher ( https://www.nature.com/articles/d41586-023-01047-4 )
https://twitter.com/LongDesertTrain/status/1708301438642729378

I think this preprint, by @Stuartturville , is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48
https://threadreaderapp.com/thread/1705385838207750579.html

... https://threadreaderapp.com/thread/1708301438642729378.html

The Nobel Prize @NobelPrize | 5:45 AM · Oct 2, 2023:

BREAKING NEWS
The 2023 #NobelPrize in Physiology or Medicine has been awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.

Image ( https://twitter.com/NobelPrize/status/1708780262883017166/photo/1 )
-----------------------------------------------

PRESS RELEASE
https://www.nobelprize.org/prizes/medicine/2023/press-release/
-----------------------------------------------

'Redemption': How a scientist's unwavering belief in mRNA gave the world a Covid-19 vaccine
Sarah Newey and Paul Nuki | 2 December 2020
https://www.telegraph.co.uk/global-health/science-and-disease/redemption-one-sci...
_____________________________________
ETA:

Tim Stearns @StearnsLab | 7:35 AM · Oct 2, 2023:
Professor and Dean at The Rockefeller University. Cell biologist...

Congratulations to Karikó and Weissman! The 2005 paper that is the basis for the award has a simple hypothesis - that modified bases prevent the immune response to exogenous RNA - which is then tested by well-designed experiments. A classic.
Image ( https://twitter.com/StearnsLab/status/1708807829543362953/photo/1 )

Katalin Karikó et al. 2023. Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity, Volume 23, ISSUE 2, P165-175, August 2005. Open Archive. DOI:https://doi.org/10.1016/j.immuni.2005.06.008 https://cell.com/immunity/fulltext/S1074-7613(05)00211-6

Rebecca Owen et al. 2023. Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey. Quality of Life Research. Open Access. Published: 22 September 2023.
https://doi.org/10.1007/s11136-023-03513-y https://link.springer.com/article/10.1007/s11136-023-03513-y

Abstract
Purpose. The complexity of long COVID and its diverse symptom profile contributes to unprecedented challenges for patients, clinicians, and healthcare services. The threat of long COVID remains ignored by Governments, the media and public health messaging, and patients’ experiences must be heard through understanding of the lived experience. This study aimed to understand the lived experience of those living with long COVID.

Methods. An online web-based survey was designed using Patient and Public Involvement and Engagement (PPIE) to increase understanding of the lived experiences of long COVID, and was distributed through PPIE groups, social media, and word of mouth. The survey used closed and open questions relating to demographics, pre- and post-COVID-19 health quality of life, daily activities and long COVID experiences.

Results. Within our sample of 132 people living with long COVID, the findings highlight that individuals are being severely impacted by their symptoms and are unable to or limited in participating in their daily activities, reducing quality of life. Long COVID places strain on relationships, the ability to live life fully and is detrimental to mental health. Varying health care experiences are described by participants, with reports of medical gaslighting and inadequate support received.

Conclusions. Long COVID has a severe impact on the ability to live life fully, and strains mental health. The appropriate mechanisms and support services are needed to support those living with long COVID and manage symptoms.

Fig 3 Patient recommendations for HCP helping PwLC to enhance HRQoL
https://link.springer.com/article/10.1007/s11136-023-03513-y/figures/3

Tea inactivates COVID, incl Omicron sub-variants?!

Masaharu Shin-Ya et al. 2023. Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2. (NATURE) Scientific Reports volume 13, Article number: 16577 (3 Oct 2023) Open Access. https://www.nature.com/articles/s41598-023-43563-3#Sec10

Abstract
The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (−)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly suppressed infectivity of BA.1 and XE subvariants, while effect on BA.2.75 was weaker. Neutralization assay showed that EGCG and TFDG inhibited interaction between BA.1 RBD and ACE2. In silico analyses suggested that N460K, G446S and F490S mutations in RBDs crucially influenced the binding of EGCG/TFDG to the RBDs. Healthy volunteers consumed a candy containing green tea or black tea, and saliva collected from them immediately after the candy consumption significantly decreased BA.1 virus infectivity in vitro. These results indicate specific amino acid substitutions in RBDs that crucially influence the binding of EGCG/TFDG to the RBDs and different susceptibility of each Omicron subvariant to EGCG/TFDG. The study may suggest molecular basis for potential usefulness of these compounds in suppression of mutant viruses that could emerge in the future and cause next pandemic.

Stephen M. Kissler et al. 2023. Viral kinetics of sequential SARS-CoV-2 infections. Nature Communications volume 14, Article number: 6206 (5 Oct 2023) Open Access. https://www.nature.com/articles/s41467-023-41941-z

Abstract
...evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.

Discussion
...In conclusion, immunity from a first SARS-CoV-2 infection affects the viral kinetics of a second SARS-CoV-2 infection principally by speeding up viral clearance and thus shortening the overall time of acute infection. The kinetics of a second BA.1/BA.2 infection are unaffected by the lineage of the first infection. Individuals who quickly cleared their first infection also generally tended to quickly clear their second infection, despite a high degree of variation in individual clearance times, pointing towards persistence of underlying immune response across multiple infections. These findings help guide the interpretation of quantitative SARS-CoV-2 tests both clinically and for surveillance and point towards persistent individual-level immune mechanisms against SARS-CoV-2 that so far remain unexplained.

Anton Gerashchenko @Gerashchenko_en | 7:16 AM · Oct 5, 2023:

Ukrainian partisans in Crimea report that they successfully got inside Russian fortifications located not far from Feodosia {a town of regional significance on the Crimean coast of the Black Sea}.

Partisans reported discovering and recording secret Russian positions and firing points.
0:56 ( https://twitter.com/Gerashchenko_en/status/1709890220361916451 )

Worthwhile read: Michael Mina, formerly with Harvard, perhaps most famous for uncovering measles-erasure of immune memory and EBV-MS connection, is interviewed re "the nature of the pandemic off-ramp — and about everything else we should’ve known about the disease from the outset" (New York Times).

We Should Have Known So Much About Covid from the Start
David Wallace-Wells | Oct. 5, 2023

...{Mina} We’ve seen a dramatic reduction in mortality. We’ve even seen, I’d say, a dramatic decline in rates of serious long Covid per infection.

But I do think it’s going to be a while before this virus becomes completely normal. And I’ve never been convinced that this current generation of elderly people will ever get to a place where it is completely normal. If you’re 65 or 75 or even older — it’s really hard to teach an immune system new tricks if you’re that age. And so while we may see excess mortality in the elderly decline somewhat, I don’t think we’ll see it ever disappear for this generation who was already old when the pandemic hit. Many will never develop that robust, long-term immunological memory we would want to see — and which happens naturally to someone who’s been exposed hundreds of times since they were a little baby.

For babies born today, though, I really think they’re not going to view Covid as any different than other viruses. By the time they are 20, it will be like any other virus to them. Because their immune systems will have grown up with it.

...{DWW} My understanding is that the best data on long Covid prevalence comes from the U.K.’s Office of National Statistics, which shows a much lower risk of developing long Covid now, from reinfection, than from an initial infection earlier in the pandemic.

{MM}I think the worst is behind us. By far. But I know multiple people, very close to me, who are dealing with really severe long Covid. Some of them have amorphous symptoms, but haven’t been able to work for a few years. Some have very significant heart disease. One person is in surgery right now today, from an infection a few years ago. But the worst is definitely behind us, which is a good thing, especially for people who worry that the problems will keep building and a lot of people — or even everyone — will get long Covid symptoms. I don’t think there’s a world where we’re looking at the babies of today dealing with long Covid at any meaningful scale.

{DWW} My understanding is that, for long Covid at least, the large majority are relatively well recovered within a year.

{MM} Yes, that’s right. But a lot of the fear right now comes from the worst cases, and there’s a lot of worst cases. Even one of the people that I know well, I know in their mind they’re worried that they’ll never recover, but I think objectively they are recovering slowly. It might not be an eight month course. It might be a year and a half. But they will get better. Most of us will.

Gift article via https://twitter.com/dcscheer/status/1710136182430921144
i.e.,
https://www.nytimes.com/2023/10/05/opinion/covid-pandemic-michael-mina.html?unlo...

Eric Topol @EricTopol | 5:08 PM · Oct 5, 2023:

Now we're talking!
A trivalent nasal vaccine vs mumps, measles and Covid, broadly effective vs #SARSCoV2 variants, with expected long duration (using preS-6P), in multiple experimental models

@PNASNews
Text first page highlighted ( https://twitter.com/EricTopol/status/1710039363701346769/photo/1 )
-------------------------------------------

Jiayu Xu et al. 2023. A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern. PNAS October 5, 2023, 120 (41) e2220403120 https://doi.org/10.1073/pnas.2220403120 https://pnas.org/doi/10.1073/pnas.2220403120

ABSTRACT
...This vaccine candidate is based on three components of the MMR vaccine, a measles virus Edmonston and the two mumps virus strains Jeryl Lynn 1 (JL1) and JL2 that are known to provide safe, effective, and long-lasting protective immunity. The six proline-stabilized prefusion S protein (preS-6P) genes for ancestral SARS-CoV-2 WA1 and two important SARS-CoV-2 VoCs {variants of concern} (Delta and Omicron BA.1) were each inserted into one of these three viruses which were then combined into a trivalent “MMS” candidate vaccine. Intranasal immunization of MMS in IFNAR1−/− mice induced a strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, mucosal IgA, and systemic and tissue-resident T cells. Immunization of golden Syrian hamsters with MMS vaccine induced similarly high levels of antibodies that efficiently neutralized SARS-CoV-2 VoCs and provided broad and complete protection against challenge with any of these VoCs. This MMS vaccine is an efficacious, broadly protective next-generation COVID-19 vaccine candidate, which is readily adaptable to new variants, built on a platform with a 50-y safety record that also protects against measles and mumps.

...The next-generation COVID-19 vaccine should utilize the best SARS-CoV-2 S antigen. Our trivalent vaccine uses preS-6P, the most immunogenic form of the S {spike} protein. In contrast, all current COVID-19 vaccines utilize the native full-length S or preS-2P as the vaccine antigen... Because preS-6P has much higher protein expression and is more stable compared to preS-2P, the use of preS-6P in vaccine design will significantly enhance the efficacy and longevity of immune responses

...In summary, we have developed a next-generation COVID-19 vaccine candidate that expresses the most highly optimized S antigen, preS-6P antigen, from the 3 most important SARS-CoV-2 strains delivered intranasally to induce durable mucosal IgA, serum IgG, and lung-resident memory T cell immune responses, thereby providing broad protection against SARS-CoV-2 VoCs.

Ralf Wittenbrink @RWittenbrink | 8:22 AM · Oct 6, 2023:

Translated from German by Google
that XBB. 1.5-containing mRNA vaccines are most likely to increase protection against the currently circulating #XBB subvariants and the new BA.2.86 variant...
-----------------------------------------------

Metodi V Stankov et al. 2023Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination. MedRx 5 Oct 2023. doi: https://doi.org/10.1101/2023.10.04.23296545 https://www.medrxiv.org/content/10.1101/2023.10.04.23296545v1

Preprint, not yet peer-reviewed.

Abstract
...In summary, BNT162b2 Omicron XBB.1.5 vaccination resulted in potent neutralizing antibody responses against Omicron XBB variants, including the recent Omicron variants EG.5.1 (Eris) and BA.2.86 (Pirola), as well as XBB.1.5 reactive T cell responses, suggesting that booster vaccination will augment protection against these emerging variants.

Osterholm Update
Episode 141: One Huge Puzzle (58:44--start at 7 min)
Dr. Michael Osterholm* | October 5, 2023

In "One Huge Puzzle," Dr. Osterholm and Chris Dall discuss the state of the pandemic in the U.S. and around the world, the rollout of the updated mRNA vaccines, and two recently published studies on long COVID. Dr. Osterholm also shares his thoughts on the updated Novavax vaccine and answers an ID Query about COVID vaccine side effects.

https://www.youtube.com/watch?v=l5AtEYMTgjc
via https://www.cidrap.umn.edu/covid-19/episode-141-one-huge-puzzle

* Director, the Center for Infectious Disease Research and Policy {CIDRAP} at the University of Minnesota

🚨WE MADE A BILLBOARD HAPPEN!!!🚨
...and YOU CAN TOO! Here's a guide to MAKING THIS HAPPEN IN YOUR CITY. 🧵

Photograph. A billboard in Georgia reads, "Long Covid stole my life from me" in large letters across a black background. Small text on the billboard says "BERLIN BUYERS CLUB" and "whn.global" Billboard artwork by Sophie Dimitriou. WHN url used with permission.
https://twitter.com/RealGayArbys/status/1710402326710673689/photo/1

With the help of @pickle_juice29 , I made a guide to replicating this project in your city. Our toolkit
(https://bit.ly/billboard_toolkit) has fundraising tips, vendor ideas, & more!
Billboards 101 https://drive.google.com/file/d/1qBVFujh8QisaKAiTc8L8ngJfJJwSZXzH/view

And our artist, @sophsoph_psd , has made her design open source (https://bit.ly/billboard_designs) so you can use it.

This didn't cost thousands of dollars! Two digital billboards in Georgia only cost *$125* for a 20-day ad campaign (made entirely possible by the generosity of @pickle_juice29 !)
We went through Blip, which is surprisingly affordable & straightforward: https://www.blipbillboards.com/

Our goal is to encourage other activists & organizations to replicate this project so we can spread the word about Long Covid. According to Blip, 90,000 people have driven past this billboard so far. This type of messaging reaches diverse audiences. It's tangible & loud & BIG.

Shoutout to @TheWHN for generously allowing us to include a link to http://whn.global, where people can learn the truth about the pandemic (and how to stay safe). And a big thank you to @BerlinBuyers + @sophsoph_psd
for creating this powerful design.

- lizwhatsherface.bsky @RealGayArbys | 5:11 PM · Oct 6, 2023

Opinion: Sick of your kids being sick? Clean air in schools may be the answer
It’s time to take a closer look at air filters in classrooms to prevent illnesses and absences
Julia Corey and Orla Hegarty | 7 Oct 2023

...In May, the Health and Safety Authority (HSA) published a new code of practice for indoor air quality. Under this guidance, which has been signed into law, all classrooms and workplaces should consistently have CO2 levels under 1,000ppm...

https://www.irishexaminer.com/opinion/commentanalysis/arid-41242243.html

AndersHviid @anders_hviid | 1:17 AM · Oct 11, 2023:
Head of Epidemiology Research (@SSI_AEF ) at @SSI_dk & Prof. of PharmacoEpi at @UCPH_health 🇩🇰.
https://twitter.com/anders_hviid/status/1711974305095929987

🚨New study out 🚨 in @NatureComms*
What was the impact of Covid-19 on post-acute sick leave in 🇩🇰?
...➡️4.5% of infected individuals reported substantial sick leave
...We identified subgroups who were particularly susceptible to substantial sick leave:
➡️females,
➡️50–65-yr-olds,
➡️obesity, chronic lung diseases, and fibromyalgia
...We conclude that Covid-19 infection was associated with substantial post-acute sick leave even in non-hospitalized cases.
🧵

*Elisabeth O’Regan et al. 2023. A hybrid register and questionnaire study of Covid-19 and post-acute sick leave in Denmark. Nature Communications volume 14, Article number: 6266 (7 Oct 2023) Open access https://www.nature.com/articles/s41467-023-42048-1

Abstract
Post-acute sick leave is an underexplored indicator of the societal burden of SARS-CoV-2. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which include 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index- and alpha-dominant waves. We observe that an additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave is defined as more than 1 month of sick leave within the period 1–9 months after the RT-PCR test date. Being female, 50–65 years, or having certain pre-existing health conditions such as obesity, chronic lung diseases, and fibromyalgia each increase risk for taking substantial sick leave. Altogether, these results may help motivate improved diagnostic and treatment options for persons living with post-Covid conditions.

Monika Marko & Rafał Pawliczak 2023. Assessment of the available therapeutic approaches for severe COVID-19: a meta-analysis of randomized controlled trials. Scientific Reports volume 13, Article number: 17114 (10 )ct 2023) Open access. https://www.nature.com/articles/s41598-023-44463-2

Abstract
...anakinra, remdesivir, baricitinib, ivermectin, ritonavir {Paxlovid}, tocilizumab, sarilumab, sotrovimab, casirivimab/imdevimab...We obtained the most statistically significant outcomes favorable tocilizumab* compared to SoC {standard of care} ...This meta-analysis has revealed that a considerable amount of research characterized by a very diverse methodology is available. Despite the limited data that met the criteria for inclusion in the meta-analysis, we showed that the available treatment options for severe COVID-19 are effective.

...Conclusion
Considering the statistical aspect of our study, due to the statistical significance and heterogeneity values, tocilizumab was the best given the number of deaths, number of patients needing mechanical ventilation, and number of patients discharged from the hospital compared to SoC. It should be noted that the most significant number of comparisons (for several endpoints) were made for remdesivir, anakinra, and tocilizumab, which proves that the studies on them are the most consistent. The results relate to WHO recommendations3 for severe COVID-19, where tocilizumab is recommended. This meta-analysis has revealed many COVID-19 studies characterized by a very different methodology. Therefore, the results of this study should be interpreted with caution. Despite the limited data that met the criteria for inclusion in the meta-analysis, we showed that the available treatment options for severe COVID-19 are effective and can be safely used.
----------------------------------------------------------

*Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 receptor. Wikipedia
______________________________________________

A peek into academic discussions re Paxlovid effectiveness:

Ilan Schwartz MD PhD @GermHunterMD | 2:47 PM · Oct 11, 2023:
ID infectious disease}doctor & researcher @DukeAdultID...; assoc editor @CIDjournal Clinical Infectious Diseases}

Didyaknow? EPIC-SR* has resulted @JGPharmD {ID pharmacy professor} with 🫖 {?}
Outpatient paxlovid didn’t ⬇️ Covid-related hospitalization & death in unvacc’d patients with standard risk or vaccinated high-risk patients (unlike in prevax era)
Are these still right endpoints?

#IDWeek2023 #MedIQ23IDWeek
Bar graph showing decrease in Covid-related hospitalization and death in epic hr (seronegative and high risk seropositive) but not epic sr (vaccinated high risk and unvaccinated standard risk)

bar graph ( https://twitter.com/GermHunterMD/status/1712178053701407117/photo/1 )

{Discussion follows at https://twitter.com/GermHunterMD/status/1712178053701407117}
--------------------------------------------------

* EPIC-SR: E valuation of P rotease I nhibition for C OVID-19 in S tandard- R isk Patients study
https://clinicaltrials.gov/study/NCT05011513

Bao-Qiang Guo et al. 2023. Incidence of myopericarditis after mRNA COVID-19 vaccination: A meta-analysis with focus on adolescents aged 12–17 years. Vaccine Volume 41, Issue 28, 23 June 2023, Pages 4067-4080. https://doi.org/10.1016/j.vaccine.2023.05.049 https://www.sciencedirect.com/science/article/pii/S0264410X23006102

ABSTRACT
...Results. Fifteen studies were included. The pooled incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12–17 years were 43.5 ... cases per million vaccine doses for both BNT162b2 {Pfizer COVID-19 vaccine} and mRNA-1273 {Moderna COVID-19 vaccine}..., and 41.8 ... cases for BNT162b2 alone ... Myopericarditis was more common among males (66.0...cases) than females (10.1... cases) and among those receiving the second dose (60.4 ... cases) than those receiving the first dose (16.6...cases). The incidences of myopericarditis did not differ significantly when grouped by age, type of myopericarditis, country, and World Health Organization region. None of the incidences of myopericarditis pooled in the current study were higher than those after smallpox vaccinations and non-COVID-19 vaccinations, and all of them were significantly lower than those in adolescents aged 12–17 years after COVID-19 infection...

...5. Conclusions
The incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12–17 years were very rare; they were not higher than those after smallpox vaccinations and non-COVID-19 vaccinations and were significantly lower than those in adolescents aged 12–17 years after COVID-19 infection. These findings provide an important context for health policy makers and parents with vaccination hesitancy to weight the risks and benefits of mRNA COVID-19 vaccination among adolescents aged 12–17 years.

Kim D-H et al. 2023. Neurologic effects of SARS-CoV-2 transmitted among dogs. Emerg Infect Dis. Volume 29, Number 11—November 2023. https://doi.org/10.3201/eid2911.230804 {Early release. Any changes will be reflected in the online version in the month the article is officially released.}

Abstract
...SARS-CoV-2 can induce brain pathology in humans and other hosts...we used a canine transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2–infected dogs, particularly involving blood–brain barrier damage resembling small vessel disease...Furthermore, we detected...a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2–associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.

...Discussion...
_________________________________________

Ontario:

"since there is still so much uncontrolled transmission of the virus, it is constantly mutating to evade immunity built up by previous variants which can lead to some people becoming reinfected again within weeks not months or years...If you have been infected, don't assume you have months of protection before the next infection and increase risky
behaviour of exposure thinking you are safe. You might be getting all the damage from the virus and very little protection."

- Jeff Gilchrist (Senior AI Data Scientist at the Children's Hospital of Eastern Ontario (CHEO) Research Institute)

https://twitter.com/jeffgilchrist/status/1713602505865572458

Fabio Angeli e al. 2023. Global burden of new-onset hypertension associated with severe acute respiratory syndrome coronavirus 2 infection. European Journal of Internal Medicine, Available online 16 October 2023. In Press, Corrected Proof. https://doi.org/10.1016/j.ejim.2023.10.016 https://www.sciencedirect.com/science/article/pii/S0953620523003710

ABSTRACT
...Overall, COVID-19 was associated with a 65% increased risk of new-onset hypertension when compared with controls ...; furthermore, incidence of new-onset hypertension was 9% and 5% among COVID-19 patients and controls, respectively. In both the acute phase and recovery from infection, the interaction between spike proteins of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) receptors remain the most plausible mechanism explaining the raise in BP (ranking new onset hypertension as one of the most prevalent cardiovascular sequelae of COVID-19). In this area of research, it is worth to mention that new variants of SARS-CoV-2 exhibit specific mutations in the spike protein that promotes entry into viral cells via ACE2. Thus, the enhanced spike affinity for ACE2 of new variants has the potential to increase the risk of new-onset hypertension when compared with the original Wuhan strain.

Eric Topol @EricTopol | 9:34 AM · Oct 19, 2023:
How #SARSCoV2 can rev up atherosclerosis in the coronary artery and plaque instability
-------------------------------------------

Mauro Giacca 2023. SARS-CoV-2 infection boosts inflammation in atherosclerotic plaques. Nature Cardiovascular Research (18 Oct 2023) https://www.nature.com/articles/s44161-023-00358-z

The incidence of acute cardiovascular events, including myocardial infarction and ischemic stroke, is increased in individuals with COVID-19. A study shows that SARS-CoV-2 can directly infect macrophages and foam cells in atherosclerotic plaques and contribute to plaque instability.

Fig 1 Covid-19 infects coronary vessel lesions ( https://twitter.com/EricTopol/status/1714998367279817012/photo/1 )

Alex Qinyang Liu et al. 2023. SARS-CoV-2 infection correlates with male benign prostatic hyperplasia deterioration. Journal of Internal Medicine. First published: 18 October 2023. Open Access
https://doi.org/10.1111/joim.13719 https://onlinelibrary.wiley.com/doi/10.1111/joim.13719

Abstract
...Conclusions. SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.

...DISCUSSION
... even patients with asymptomatic or mild infection, which represents the majority of the COVID-19 population, can still be affected by SARS-CoV-2 urologically and suffer from BPH {male benign prostatic hyperplasia} complications...

Pfizer to price Covid drug Paxlovid at $1,390 per course
Annika Kim Constantino | Oct 18 2023

Key Points
Pfizer will price a five-day course of its Covid antiviral drug Paxlovid at $1,390 when the company starts to sell it on the commercial market later this year.
A company spokesperson on Wednesday confirmed the price, which was first reported by the Wall Street Journal.
But health insurance plans will likely pay much less than the nearly $1,400 list price for Paxlovid, meaning patients will probably have small or no out-of-pocket costs....

https://www.cnbc.com/2023/10/18/pfizer-to-price-covid-drug-paxlovid-at-1390-per-...

Yi Mu etal. 2023. Healthcare Utilisation of 282,080 Individuals with Long COVID Over Two Years: A Multiple Matched Control Cohort Analysis. The Lancer preprints. 29 Pages Posted: 19 Oct 2023 https://papers.ssrn.com/sol3/papers.cfm

Preprint. Not yet reviewed.

Abstract
Background: In the UK alone, long Covid(LC) has affected over 2 million individuals...

Findings: ...Healthcare utilisation of the LC group increased progressively between 2020 and 2023, compared to controls.

...Discussion
In the first national study of healthcare utilisation in individuals with LC to consider a range of
control populations, we have three main findings. First, despite low mortality rates, we showed
that individuals with LC had the highest healthcare utilisation over 2 years across GP, ED and OP*
care, and the second highest rates of hospital and critical care admission (after individuals with
COVID and without LC), compared with pre-pandemic and pandemic control groups. Second, LC
care was estimated to cost over £3000 (~USD 3750) per person per year, nearly four times more
than care in the same individuals before the pandemic, and nearly three times as much as care
in age- and comorbidity-matched individuals before and during the pandemic. Third, most of the
LC healthcare burden was in the first 2 months post-diagnosis, but persisted over the following
two years, whether primary care, OP or IP...

* GP: General Practice; OP: Outpatient; IP: Inpatient; ED: Emergency Department

Orla Hegarty @Orla_Hegarty | 4:37 AM · Jan 23, 2021:
Architect Asst Professor @UCDDublin @UCDArch
https://twitter.com/Orla_Hegarty/status/1352913377094475776
(Thread) Learning from #COVID19 #superspread

🇺🇸USA Skagit Choir practice: 1 person with mild symptoms, 2.5-hours indoors, 50 infected, 2 deaths
“you can be inhaling what someone else exhaled even if they are far away from you” 1/
https://scholar.colorado.edu/concern/articles/n583xw008

🇰🇷 South Korea, restaurant #Covid19 #superspread
CCTV shows 1 person infected another seated 6 metres away within 5 mins
“person was seated near a ceiling-type air conditioner, which blew virus droplets” 2/
https://www.verywellhealth.com/air-flow-covid-19-restaurant-outbreak-5090663

🇩🇪 Germany, meat factory #Covid19 #superspread
1,500 workers infected, indoors at 10°C low humidity
“Cold & stale air conditions allowed coronavirus particles to travel more than 8 meters” 3/
https://www.bloomberg.com/news/articles/2020-07-23/virus-can-jump-26-feet-at-col...

🇻🇳 Vietnam 10 hour flight #COVID19 #superspread
1 passenger infected 15 on same plane (no masks)
“12 were sitting in business class, along with patient, where seats are spread further apart, 2 in economy & 1 crew” 4/ https://independent.co.uk/travel/news-and-advice/coronavirus-flight-transmission... & https://wwwnc.cdc.gov/eid/article/26
https://www.independent.co.uk/travel/news-and-advice/coronavirus-flight-transmis...

🇨🇳 China, restaurant #Covid19 #superspread
Infection of 10 persons from 3 families who had eaten at separate tables in air-conditioned restaurant
“key factor for infection was the direction of the airflow” 5/
https://wwwnc.cdc.gov/eid/article/26

🇦🇺 Australia, nursing homes
CO2 carbon dioxide in some homes over 3 times recommended level, meaning poor ventilation
“If anyone in building is infected, risk of cross-infection may be significant even if PPE protocols followed & surfaces cleaned” 6/
https://theconversation.com/poor-ventilation-may-be-adding-to-nursing-homes-covi...

🇺🇸 Washington, Capitol Building #Covid19
200 national guard & 3 lawmakers infected
“committee room lockdown had all ingredients for #superspread event.. overcrowding, hours indoors, people without masks & low ventilation” 7/
https://washingtonpost.com/politics/capitol-riot-coronavirus-lockdown-room-super... & https://newsweek.com/hundreds-natio

🇸🇪 Sweden, hospital
#COVID19 detected in central ventilation systems, distant from patient areas, indicating it can be transported long distances
“increased infection indoors, as well as #superspread, could be explained by airborne transmission” 8/
https://www.nature.com/articles/s41598-020-76442-2

🇰🇷 South Korea, Call Centre #superspread
97 infected in open office
“virus can be exceptionally contagious in crowded offices.. despite considerable interaction between workers in the building #COVID19 spread limited almost exclusively to 11th floor” 9/ https://wwwnc.cdc.gov/eid/article/26

🇰🇷 South Korea, coffee shop
27-person cluster linked to ceiling mounted air-conditioning in coffee outlet
“4 mask-wearing employees escaped infection... masks may not provide 100% protection, but there’s nothing out there that’s as effective” 10/
https://fortune.com/2020/08/25/covid-outbreak-starbucks-seoul-masks-employees/

🇫🇷 France, aircraft carrier (ship) #Covid19 #superspread
668 out of nearly 2,000 sailors infected
“Proximity & contagion make for dangerous shipmates. We have already seen how deadly virus can be in close confines of cruise ships” 11/
https://www.bbc.com/news/world-europe-52308073

🇳🇿 New Zealand, quarantine hotel #superspread
29 mariners, 2 health workers
“poor ventilation & double-bunking helped spread Covid... with poor ventilation in corridors, factors all added up to being conducive to inhalation of #Covid19 aerosols” /12
https://www.stuff.co.nz/national/health/coronavirus/124026191/poor-ventilation-a...

🇮🇪Ireland, airplane #COVID19 #superspread
13 on flight (59 total)
“4 of flight cases were not seated next to any other positive case, had no contact in the transit lounge, wore face masks in-flight & were not ‘close contacts’ under ECDC definition” 13/
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.42.2001624

🇨🇦 Canada, Seniors Residence #COVID19 #superspread
156 residents & 91 staff infected
“infectious disease experts & an air quality specialist determined the ventilation system was malfunctioning” /14
https://globalnews.ca/news/6940893/staff-infected-vigi-mont-royal-residence-vent...
{margd: Geez, could this be the outbreak that killed Bernice, my cousin's sweet MIL?}

🌎 Global, Conference #COVID19
20,000 may have acquired conference virus
“ #superspread is hallmark of coronavirus. When infected person shows up —inside, with poor ventilation & close contact— virus can infect a lot of people in very little time” /15
https://www.nytimes.com/2020/08/26/health/covid-19-superspreaders-boston.html

🇳🇱 Netherlands, Care Home
#suprspread
17 residents & 17 staff, at time of low virus infection in local community
“data suggest that this outbreak is caused by aerosol transmission of #COVID19 in a situation of inadequate ventilation” /16
https://academic.oup.com/cid/article/73/1/170/5898577

🇮🇱 Israel, school #Covid19 #superspread
153 students, 25 staff & 87 cases among close contacts
‘during extreme heatwave, air-conditioning functioned continuously in all classes’ & a ‘face mask exemption’ /17
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384285/

🇻🇳 Vietnam, bar
19 infected
“Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission” /18 https://wwwnc.cdc.gov/eid/article/27

🇨🇳 China, bus #superspread
1 person infected 23 (of 67) passengers on 100 minute round trip
“prevention & control must consider airborne spread of #COVID19 which is a highly transmissible pathogen in closed environments with air recirculation” 19/
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2770172
.
.
.
🇨🇦Canada, convent #superspread
46 cases, 9 deaths
“#COVID19 has been cited in the deaths of dozens of retired or infirm nuns who lived in congregate settings” /49
https://abcnews.go.com/Health/wireStory/retired-nuns-michigan-die-covid-19-janua...

Time to mask and vaxx up!
(I think similar rates in n US at least. In summer, Ontario was lagging NY.)

Jeff Gilchrist @jeffgilchrist | 7:14 AM · Oct 22, 2023:
PhD Biomedical researcher, data scientist...{Children's Hospital of Eastern Ontario, Ottawa}

If there are 1 in 23 people infected {with COVID} in Ontario like @MoriartyLab {U Toronto} estimates {below}, that means any group of 10 people has a 36% chance at least 1 person is infected, increases to almost 50% for 15 people and 67% for 25 people. Online calculator available here: https://tinyurl.com/2emnj8nj

Graph: https://twitter.com/jeffgilchrist/status/1716050279450185985/photo/1
-----------------------------------------------------------------

Tara Moriarty @MoriartyLab | 11:59 PM · Oct 21, 2023
Assoc Prof @UofT {U Toronto} Bloodborne infections, Lyme disease, misinfo.

Canadian COVID Forecast Oct 21-Nov 3, 2023
ONTARIO SEVERE (increasing) About 1 in every 23 people infected Compared to lowest point of pandemic in Canada:
-Infections ~18X higher
-Long COVID ~13X higher
-Hospitalizations ~11X higher
-Deaths ~20X higher

Cdn COVID Forecast 21 Oct- 3 Nov 2023 ( https://twitter.com/MoriartyLab/status/1715940965184143600/photo/1 )

So as we await more studies, I'm wondering if it wouldn't hurt/might help LC patients to eat more tryptophan (whole milk, canned tuna, turkey and chicken, oatmeal), and to supplement w anti-inflammatory such as curcumin (extract of turmeric)?

A Crucial Pattern Behind Long COVID May Have Been Identified
Clare Watson | 22 October 2023

A new study pointing to reduced levels of a well-known chemical messenger in people with long COVID has landed on a pathway that unites several possible causes of the disabling condition...increased blood clotting, a lingering virus, persistent inflammation, and a dysfunctional nervous system}... could explain the cognitive difficulties and memory loss people with long COVID report. Not only that, the study could point the way toward possible treatments if the results are replicated in larger cohorts.

...The connection they propose goes like this: lingering viral material could trigger the body's immune system to pump out interferons, a group of signaling proteins involved in anti-viral defenses.

This drives inflammation, which limits the absorption of tryptophan, an amino acid used to make serotonin, in the gut.

Persistent inflammation also messes with platelets, blood cells involved in blood clotting that also carry serotonin around the body.

Less circulating serotonin then impairs the activity of the vagus nerve, the body's superhighway sending signals between the brain, gut, and other organs.

...In mice, low serotonin levels and reduced vagus nerve activity from a viral infection resulted in the animals performing worse on memory tests.

Yet remarkably, those memory impairments – which resemble but obviously don't replicate the cognitive troubles of long haulers – could be prevented when serotonin levels were restored.

More human studies are needed to test those suggestions. Future research also needs to resolve why some people in a second cohort of long COVID patients, possibly with milder symptoms, didn't have low serotonin levels...

https://www.sciencealert.com/a-crucial-pattern-behind-long-covid-may-have-been-i...
----------------------------------------------

Andrea C. Wong et al. 2023. Serotonin reduction in post-acute sequelae of viral infection. Cell, 16 Oct 2023. Open Access. DOI:https://doi.org/10.1016/j.cell.2023.09.013 https://www.cell.com/cell/fulltext/S0092-8674(23)01034-6

Sarah C. J. Jorgensen et al. 2023. Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy. JAMA Pediatr. Published online October 23, 2023. doi:10.1001/jamapediatrics.2023.4499 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2810937
-----------------------------------------------------------

Editorial:

Catherine Mary Healy and Laura E. Riley 2023. Safety and Benefits of COVID-19 Vaccination in Pregnancy—Implications for the Maternal Vaccination Platform. JAMA Pediatrics. Published online October 23, 2023. doi:10.1001/jamapediatrics.2023.4496 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2810941

...The most compelling factor influencing a pregnant woman’s decision against being vaccinated in pregnancy is concern regarding the safety of the intervention for the infant. In this issue of JAMA Pediatrics, Jorgensen and colleagues provide considerable evidence that this concern is unfounded for COVID-19 vaccination. In a well-designed, population-based, retrospective cohort study of live births in Canada, investigators studied 142 006 singleton, live births, 60% of whom had been born to mothers who received 1 or more messenger RNA (mRNA) COVID-19 vaccine doses during pregnancy and compared them with the infants of unvaccinated women. Other studies have assessed short-term neonatal outcomes, but this study attempted to assess a broader range of outcomes and extended follow-up to 6 months of age.

...The findings reported by Jorgensen and colleagues are striking and reassuring, confirming the benefit of this intervention. The risks of severe neonatal morbidity, neonatal death, and admission to the neonatal intensive care unit were all significantly lower in infants of vaccinated mothers, with an adjusted risk ratio (ARR) of 0.86... for severe neonatal morbidity, an ARR of 0.47 ... for death, and an ARR of 0.86 ... for neonatal intensive care unit admission.

Infants of vaccinated mothers did not have higher rates of readmission in the neonatal period up to 6 months of age. Results were unaffected by number of vaccine doses, trimester of maternal vaccination, type of mRNA vaccine received, or infant sex.

The significance of these findings in this analysis compared with those of other studies lies in the robust number of participants, high vaccination rate of mothers, inclusion of a greater proportion of maternal-infant pairs vaccinated in the first trimester (a period where both pregnant women and health care providers may be hesitant to vaccinate), and duration of infant follow-up. These all combine to provide considerable evidence of the safety of COVID-19 vaccination...

Interesting read:

The 60-Year-Old Scientific Screwup That Helped Covid Kill
All pandemic long, scientists brawled over how the virus spreads. Droplets! No, aerosols! At the heart of the fight was a teensy error with huge consequences.
Megan Molteni | May 13, 2021

...superspreading events in restaurants, call centers, cruise ships, and a choir rehearsal, instances where people got sick even when they were across the room from a contagious person. The incidents contradicted the WHO’s main safety guidelines of keeping 3 to 6 feet of distance between people and frequent handwashing. If SARS-CoV-2 traveled only in large droplets that immediately fell to the ground, as the WHO was saying, then wouldn’t the distancing and the handwashing have prevented such outbreaks? Infectious air was the more likely culprit, {aerosol scientists} argued. But the WHO’s experts appeared to be unmoved. If they were going to call Covid-19 airborne, they wanted more direct evidence—proof, which could take months to gather, that the virus was abundant in the air. Meanwhile, thousands of people were falling ill every day.

...{Medical text} books {that Linsey Marr, an aerosol scientist at Virginia Tech and one of the few in the world who also studies infectious diseases} flipped through drew the line between droplets and aerosols at 5 microns. A micron is a unit of measurement equal to one-millionth of a meter. By this definition, any infectious particle smaller than 5 microns in diameter is an aerosol; anything bigger is a droplet. The more she looked, the more she found that number. The WHO and the US Centers for Disease Control and Prevention also listed 5 microns as the fulcrum on which the droplet-aerosol dichotomy toggled.

There was just one literally tiny problem: “The physics of it is all wrong,” Marr says. That much seemed obvious to her from everything she knew about how things move through air. Reality is far messier, with particles much larger than 5 microns staying afloat and behaving like aerosols, depending on heat, humidity, and airspeed. “I’d see the wrong number over and over again, and I just found that disturbing,” she says. The error meant that the medical community had a distorted picture of how people might get sick...

...after {Harvard engineer named William Firth Wells author of "Airborne Contagion and Air Hygiene"} (1955)} died, scientists inside the CDC conflated his observations. They plucked the size of the particle that transmits tuberculosis out of context, making 5 microns stand in for a general definition of airborne spread. Wells’ 100-micron threshold got left behind. “You can see that the idea of what is respirable, what stays airborne, and what is infectious are all being flattened into this 5-micron phenomenon,” {Katie Randall, citation tracker, a type of scholastic detective work} says. Over time, through blind repetition, the error sank deeper into the medical canon...

https://www.wired.com/story/the-teeny-tiny-scientific-screwup-that-helped-covid-...

>128 margd: contd. (aerosols, indoor air)

60 Minutes @60Minutes | 3:00 PM · Oct 26, 2023:
When COVID-19 surfaced in 2020, the medical field missed something, and it cost lives.

Airborne viruses can travel much further than originally thought. To curb infection, we should have focused on indoor air systems. @DrLaPook reports, Sunday (29 Oct 2023). http://60Minutes.com

The “original sin” of the pandemic
Watch 60 Minutes Sundays on CBS, or anytime on @paramountplus and https://cbsn.ws/34D1mLY
0:27 ( https://twitter.com/60Minutes/status/1717617200360542443 )

>43 margd: Preprint published

COVID Coronary Plaque Infection Confirms CV {Cardiovascular} Risk
Sue Hughes and Allison Shelley | October 23, 2023

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

..."This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we're seeing so much heart disease in COVID patients," Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston, told Medscape.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both {senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at New York University's Grossman School of Medicine} and Hotez said they believe this may be a specific COVID effect.

...Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. "But I can't think of another virus that stimulates the sequence of events in coronary artery inflammation like we're seeing here."

Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. "These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza," he suggested.

https://www.medscape.com/viewarticle/997638
-------------------------------------------------------------

Natalia Eberhardt et al 2023. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels. Nature Cardiovascular Research volume 2, pages 899–916 (28 Sept 2023). https://www.nature.com/articles/s44161-023-00336-5

>131 margd:

This study found during contact tracing that someone got infected after using a shared bathroom 40 minutes after the index case left. A good example of it isn't just the people currently there in a public bathroom you need to worry about
- Jeff Gilchrist {Children's Hospital of E Ontario} @jeffgilchrist | 9:24 AM · Oct 29, 2023

Jiwon Jung et al. 2021. Nosocomial Outbreak of COVID-19 in a Hematologic Ward. Infect Chemother. 2021 Jun;53(2):332-341. English. https://doi.org/10.3947/ic.2021.0046 https://icjournal.org/DOIx.php?id=10.3947/ic.2021.0046

Study: Regardless of variant, half of long-COVID patients fail to improve after 18 months (News brief)
Stephanie Soucheray | October 30, 2023
https://www.cidrap.umn.edu/covid-19/study-regardless-variant-half-long-covid-pat...
---------------------------------------------------
Jane Agergaard et al. 2023. Long-term Prognosis at 1.5 years after Infection with Wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron Variants. Intl J of Infectious Diseases Open Access, Published:October 29, 2023. DOI:https://doi.org/10.1016/j.ijid.2023.10.022 https://www.ijidonline.com/article/S1201-9712(23)00760-9/fulltext

Highlights
Trajectory of long COVID in SARS-CoV-2 wild-type, Alpha, Delta, and Omicron
Similar patterns of symptoms and severity of long COVID across all four variants
No clinically significant decline in median severity up to 1.5 years after infection
More than 50% of long COVID patients failed to improve using any outcome measure
Patients infected with Omicron may experience severe non-improving long COVID

...Discussion
...while the risk of developing long COVID 7, 12 and of getting a long COVID diagnosis following omicron is reduced..., as well as milder cases are seen ..., this study documents that some individuals were diagnosed with long COVID and experienced long COVID of the same severity following Omicron infection compared to previous variants, which are potentially not captured in population studies and studies including milder cases.

...Considering the high percentage of the population infected with the Omicron variant, ... a substantial number of patients infected with Omicron variant may develop long COVID

...we found that patients infected in the Delta and Omicron period tended to be more physical exhausted.

...half of the patients failed to experience any improve until 1.5 years after infection, regardless of SARS-CoV-2 variants and outcome measure. There was a statistically significant drop in long COVID severity from 7 to 10 months after infection... However, the median PCQ score of long COVID severity dropped less than 7 points, which were considered the MCID, and there was no further decline until 18 months after infection. Explorative analyses of the most severely affected long COVID patients confirmed that 50% failed to improve.

...we did not find different patterns of long COVID comparing variants of concern to the wild-type strain, suggesting a systemic disease with a common underlying pathophysiological mechanism.

...COVID-19 vaccination reduces the risk of long COVID

...Reinfection increases long COVID risk...

Conclusion
During the different waves of SARS-CoV-2 variants, patients referred to a Danish Post COVID Clinic at a university hospital presented with similar characteristics, symptoms, and severity of long COVID. In all variants more than half of patients failed to improve during follow-up 1.5 years after SARS-CoV-2 infection. We suggest the search for long COVID treatment options focus on these severely affected patients to develop future new treatments, which we believe will be effective across all SARS-CoV-2 variants.

Eric Topol {Scripps} @EricTopol | 5:48 PM · Oct 30, 2023:
From the @DeptVetAffairs large data resource for Covid (86% male, median age 66 yrs), there was little to show for benefit of Paxlovid for preventing most #LongCovid sequelae
Text Abstract ( https://twitter.com/EricTopol/status/1719109167334748671/photo/1 )
Fig 3 Table ( https://twitter.com/EricTopol/status/1719109167334748671/photo/2 )
--------------------------------------------

George N. Ioannou et al. 2023. Effectiveness of Nirmatrelvir–Ritonavir {Brand Name Paxlovid} Against the Development of Post–COVID-19 Conditions Among U.S. Veterans: A Target Trial Emulation. Annals of Internal Medicine. 31 Oct 2023. https://doi.org/10.7326/M23-1394 https://www.acpjournals.org/doi/10.7326/M23-1394

Abstract
...Participants: Nonhospitalized veterans in VHA (Veterans Health Administration) care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.

Intervention: Nirmatrelvir–ritonavir treatment for acute COVID-19.

Measurements: Cumulative incidence of 31 potential PCCs (post–COVID-19 conditions ) at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms.

Results: Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir–ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir–ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 ...; cumulative incidence difference, −0.29 percentage points ...).

Conclusion: Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir–ritonavir.

At least 14% of Americans have long COVID, research suggests
University College London | 2 Nov 2023
https://medicalxpress.com/news/2023-11-americans-covid.html
---------------------------------------------

David G. Blanchflower and Alex Bryson 2023. Long COVID in the United States. PLOS November 2, 2023. Open access. https://doi.org/10.1371/journal.pone.0292672 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0292672

Abstract
Although yet to be clearly identified as a clinical condition, there is immense concern at the health and wellbeing consequences of long COVID. Using data collected from nearly half a million Americans in the period June 2022-December 2022 in the US Census Bureau’s Household Pulse Survey (HPS), we find 14 percent reported suffering long COVID at some point, half of whom reported it at the time of the survey. Its incidence varies markedly across the United States–from 11 percent in Hawaii to 18 percent in West Virginia–and is higher for women than men, among Whites compared with Blacks and Asians, and declines with rising education and income. It is at its highest in midlife in the same way as negative affect. Ever having had long COVID is strongly associated with negative affect (anxiety, depression, worry and a lack of interest in things), with the correlation being strongest among those who currently report long COVID, especially if they report severe symptoms. In contrast, those who report having had short COVID report higher wellbeing than those who report never having had COVID. Long COVID is also strongly associated with physical mobility problems, and with problems dressing and bathing. It is also associated with mental problems as indicated by recall and understanding difficulties. Again, the associations are strongest among those who currently report long COVID, while those who said they had had short COVID have fewer physical and mental problems than those who report never having had COVID. Vaccination is associated with lower negative affect, including among those who reported having had long COVID.

How to measure improvement in Long COVID identified in an international consensus study
King's College London (News Release) | 2-Nov-2023

Researchers have reached an agreement on how best to measure the severity and impact of Long COVID by identifying a “Core Outcome Measure Set” (COMS).

...Dr Margaret O’Hara, from Long COVID Support said, “...this study...is important to us because we need research to measure symptoms that are relevant, and to use measurement tools that can capture our actual experience. We also need researchers around the world to use the same instruments so that studies can be compared and we can rapidly build a body of evidence to assess if treatments work...”

https://www.eurekalert.org/news-releases/1006769?
------------------------------------------------

Sarah L Gorst et al. 2023. Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study. The Lancet Respiratory Medicine, November 02, 2023. DOI:https://doi.org/10.1016/S2213-2600(23)00370-3 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00370-3/fullt...

Small, but significant, six-months post-COVID-19 changes in the vascular {and nerve?} structures of the eye compared to the pre-disease values in 20 patients with no no systemic or ocular disease. "We found statistically significant changes in choriocapillaris blood flow, subfoveal chroidal {choroidal?} thickness and retinal nerve fiber layer thickness."
---------------------------------------------------------

B. Gedik et al. 2023. Evaluation of the retina, choroid and optic disc vascular structures in individuals with a history of COVID-19Évaluation des structures vasculaires de la rétine, de la choroïde et du disque optique chez les personnes ayant des antécédents de COVID-19. Journal Français d'Ophtalmologie. Available online 2 November 2023. In Press, Corrected Proof

Summary
...Results. The mean choriocapillaris blood flow was 2.00 ± 0.13 mm2 before COVID-19 and 2.08 ± 0.23 mm2 after the disease, and the mean subfoveal choroidal thickness was 247.33 ± 7.65 μm before the disease and 273.08 ± 4.92 μm after.... The mean retinal nerve fiber layer thickness before and after COVID-19 were 119.33 ± 3.88 and 117.50 ± 3.92 μm, respectively, representing a statistically significant decrease.
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Image anatomy of eye circulation ( https://twitter.com/HarrySpoelstra/status/1721105034878840889/photo/1 )

Secondary transmission is reduced in household if COVID patient wears mask (reduced by 67%) and bed is not shared (reduced by 78%), November 21, 2020, through July 31, 2021. (margd: I'd wear N95 mask myself when in patient's vicinity, as well as exchange and filter air AMAP. I really don't want to risk Long COVID via re-infection.)

Kaiyuan Sun et al. 2023. Behavioral factors and SARS-CoV-2 transmission heterogeneity within a household cohort in Costa Rica. NATURE Communications Medicine volume 3, Article number: 102 (22 July 2023) Open access https://www.nature.com/articles/s43856-023-00325-6

Conor Browne @brownecfm | 11:50 AM · Nov 7, 2023:
Biorisk consultant specialising in COVID-19 business continuity, forecasting / analysis.
https://threadreaderapp.com/thread/1721933173725016159.html

1. There are several studies that show the potential for SARS-CoV-2 infection to activate latent TB. At the very least, this should be taken into consideration when attempting to determine why TB rates have risen to record levels.
https://www.telegraph.co.uk/global-health/science-and-disease/global-tuberculosi...

2. This is the earliest study I could find:
Mohammed Khayat et al. 2021. COVID-19 promoting the development of active tuberculosis in a patient with latent tuberculosis infection: A case report. Respiratory Medicine Case Reports Volume 32, 2021, 101344 https://www.sciencedirect.com/journal/respiratory-medicine-case-reports/vol/32/s...

3. The hypothesised mechanism of latent TB reactivation in the above study is CD4+ T-cell depletion caused by Covid-19 disease...

/end

{American Academy of Physical Medicine and Rehabilitation Clinical} Guidance Focuses on Mental Health Symptoms in Long COVID
— Multidisciplinary group calls for clinicians to reduce stigma by validating patient experiences
Michael DePeau-Wilson | November 8, 2023
https://www.medpagetoday.com/psychiatry/generalpsychiatry/107219
-------------------------------------------------

Abby L. Cheng et al. 2023. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM&R First published: 08 November 2023. Online Version of Record before inclusion in an issue. Free Access. https://doi.org/10.1002/pmrj.13085 https://onlinelibrary.wiley.com/doi/full/10.1002/pmrj.13085
___________________________________
Also:

Jonathan H. Whiteson et al. 2022. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cardiovascular complications in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM&R Volume14, Issue 7, July 2022. Pages 855-878. Free access. https://doi.org/10.1002/pmrj.12859 https://onlinelibrary.wiley.com/doi/full/10.1002/pmrj.12859

Jeffrey S. Fine et al. 2021. Multi‐disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC). PM&R Volume14, Issue1, January 2022. Pages 96-111. Free access. https://doi.org/10.1002/pmrj.12745 https://onlinelibrary.wiley.com/doi/full/10.1002/pmrj.12745

Joseph E. Herrera et al. 2021. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients.
Correction(s) for this article. PM&R Volume13, Issue12, December 2021. Pages 1439-1440. Free access. https://doi.org/10.1002/pmrj.12684 https://onlinelibrary.wiley.com/doi/full/10.1002/pmrj.12684

Joseph E. Herrera et al. 2021. Response to letter to the editor regarding “Multi-Disciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in patients with Post-Acute sequelae of SARS-CoV-2 infection (PASC)". PM&R First published: 06 October 2021. Free access. https://doi.org/10.1002/pmrj.12719 https://onlinelibrary.wiley.com/doi/full/10.1002/pmrj.12719

Scoop: Biden tells Bibi 3-day fighting pause could help secure release of some hostages
headshot
Barak Ravid | 7 Nov 2023

...According to a proposal that is being discussed between the U.S., Israel and Qatar, Hamas would release 10-15 hostages and use the three-day pause to verify the identities of all the hostages and deliver a list of names of the people it is holding, the U.S. official said.

...According to the Israeli assessment, Hamas is holding about 180 hostages, the Palestinian Islamic Jihad is holding 40 and people loosely affiliated with the militant factions are holding about 20, two Israeli officials said.

Hamas claimed in a statement on Tuesday that it was ready to release 12 foreign nationals it is holding hostage, but it couldn't because of Israel's airstrikes and ground operation.

...Netanyahu told Biden he doesn't trust Hamas' intentions and doesn't believe they are ready to agree to a deal regarding the hostages. He also said that Israel could lose the current international support it has for the operation if the fighting stops for three days...

The Israeli official told Axios that part of Netanyahu's reservation is because Hamas attacked a group of Israeli soldiers, kidnapped one of them, and killed several others during a humanitarian pause during the 2014 war...

https://www.axios.com/2023/11/07/biden-netanayhu-gaza-hamas-ceasefire-pause-host...

New study suggests gargling with salt water may be associated with lower COVID hospitalization
American College of Allergy, Asthma, and Immunology | November 9, 2023

A new study being presented at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting in Anaheim, Calif. determined that both a low- and high-dose saline regimen appeared to be associated with lower hospitalization rates compared to controls in SARS-CoV-2 infections.

"Between 2020 and 2022, individuals aged 18–65 years with positive PCR test for SARS-CoV-2 infection were randomly selected to undergo low- or high-dose saline regimens for 14 days...The low- and high-saline solutions consisted of 2.13 grams and 6 grams of salt dissolved in 8 ounces of warm water, respectively. Gargling and nasal rinsing was done four times a day for 14 days. Primary outcomes included frequency and duration of symptoms associated with SARS-CoV-2 infection; secondary outcomes included hospital or ICU admission, mechanical ventilatory support, or death. Exclusion criteria were chronic hypertension or participation in another interventional study. Those on the low- and high-dose saline solutions, as well as those in the reference population, had similar rates of vaccination."

...The hospitalization rates in the low- (18.5%) and high- (21.4%) saline regimens were significantly lower than in the reference population (58.8%.) No significant differences were noted in other outcomes among these groups.

More information: Abstract P244: Double blind randomized controlled trial of saline solution gargling and nasal rinsing in SARS-CoV-2 infection
https://annualmeeting.acaai.org/

https://medicalxpress.com/news/2023-11-gargling-salt-covid-hospitalization.html

Sweeping ban on COVID-19 vaccine mandates by private employers heads to governor
The legislation, which Republican lawmakers have been trying to pass since 2021, offers no exceptions for doctors’ offices, clinics or other health facilities.
Karen Brooks Harper | Oct. 31, 2023

...a $50,000 fine for employers who punish workers for refusing the shot.

...The legislation, which Republican lawmakers have been trying to pass since 2021, offers no exceptions for doctors’ offices, clinics or other health facilities. The bill also includes unpaid volunteers and students working in medical internships or other unpaid positions as part of graduation requirements.

Private employers are allowed by the legislation to require unvaccinated employees and contractors to wear protective gear, such as masks, or enact other “reasonable” measures to protect medically vulnerable people who work or come into their places of businesses or medical facilities.

The legislation makes it illegal, however, for any employer to take action against or otherwise place requirements on an unvaccinated employee that the Texas Workforce Commission determines would adversely affect the employee or constitute punishment...

https://www.texastribune.org/2023/10/31/texas-legislature-covid-vaccine-mandates...
----------------------------------------------

0:21 ( https://twitter.com/DrEricDing/status/1723332650104938911 )
Abbott Signs Ban on Private Employers from Mandating COVID-19 Vaccine
From The Recount

Rashmin Hira et al. 2023. Autonomic Manifestations of Long‑COVID Syndrome (Review). Current Neurology and Neuroscience Reports. Accepted 25 Oct 2023. https://link.springer.com/epdf/10.1007/s11910-023-01320-z

Astract
Purpose of Review. Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

Recent Findings. Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients.

Summary. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.

Keywords. Long-COVID syndrome · Autonomic dysfunction· Postural orthostatic tachycardia syndrome· Orthostatic hypotension· Initial orthostatic hypotension· Heart rate variability

zeynep tufekci zeynep | 9:06 AM · Nov 14, 2023:
Complex systems, wicked problems. Society, technology, science and more. Princeton professor. @NYTimes columnist.

Significant new analysis of Long Covid impact in the @UpshotNYT.
About a million people are *NEWLY* reporting cognitive difficulties, and it's driven by ages 18-49.
No other explanation besides pandemic impact makes sense — I was also looking at the same data.
Text, graph NYT ( https://twitter.com/zeynep/status/1724428479905632656/photo/1 )

First, this is monthly current population survey (CPS) data, a crucial survey. We get unemployment numbers etc. from it, which drive markets, and it is a high-quality survey with decades of data.
It's much better than some of the newer lower-quality sources with no baseline.

Second, CPS is not a Long Covid survey. It's asking specific questions it always asked.
We've long discovered merely asking people "Do you have new symptoms since having had Covid" is lousy ways to measure Long Covid. No baseline, no controls. All such surveys are unreliable.

Emmanuel @ejustin46 | 1:29 AM · Nov 17, 2023:
Fast EVOLUTION of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure
(new interesting study from @yunlong_cao and colleagues 👍)

Neutralization of B.A.2.86 against plasma from XBB BTI patients
Bar graph ( https://twitter.com/ejustin46/status/1725400862711832799/photo/1 )
------------------------------------------------

Yunlong Cao et al 2023. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure
BioRxiv 16 Nov 2023. doi: https://doi.org/10.1101/2023.11.13.566860 https://www.biorxiv.org/content/10.1101/2023.11.13.566860v1 https://www.biorxiv.org/content/10.1101/2023.11.13.566860v1.full.pdf

This article is a preprint and has not been certified by peer review

Abstract
While the BA.2.86 variant demonstrated significant antigenic drift and enhanced ACE2 binding affinity, its ability to evade humoral immunity was relatively moderate compared to dominant strains like EG.5 and HK.3. However, the emergence of a new subvariant, JN.1 (BA.2.86.1.1), which possesses an additional spike mutation, L455S, compared to BA.2.86, showed a markedly increased prevalence in Europe and North America, especially in France. Here, we found that L455S of JN.1 significantly enhances immune evasion capabilities at the expense of reduced ACE2 binding affinity. This mutation enables JN.1 to effectively evade Class 1 neutralizing antibodies, offsetting BA.2.86's susceptibility and thus allowing it to outcompete both its precursor BA.2.86 and the prevailing variants HV.1 (XBB.1.5+L452R+F456L) and JD.1.1 (XBB.1.5+L455F+F456L+A475V) in terms of humoral immune evasion. The rapid evolution from BA.2.86 to JN.1, similar to the earlier transition from BA.2.75 to CH.1.1, highlights the importance of closely monitoring strains with high ACE2 binding affinity and distinct antigenicity, despite their unremarkable immune evasion capabilities. Such strains have the potential to quickly accumulate mutations that enhance their immune escape during transmission, often at the cost of receptor binding.
----------------------------------------------------

Josette Schoenmakers @JosetteSchoenma | 5:09 PM · Nov 15, 2023:
JN.1 seems to be already dominant in Iceland and the fastest in France, Denmark and Canada as well!

I have cut off weeks that are probably less then half complete. Be aware that for Iceland, France and Canada that still means that the most recent week is incomplete.

Graphs % JN.1 recent weeks by country
https://twitter.com/JosetteSchoenma/status/1724912569293340782/photo/1
https://twitter.com/JosetteSchoenma/status/1724912569293340782/photo/2
https://twitter.com/JosetteSchoenma/status/1724912569293340782/photo/3
https://twitter.com/JosetteSchoenma/status/1724912569293340782/photo/4
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Marc Johnson @SolidEvidence | 10:34 AM · Nov 16, 2023:
Molecular virologist, Professor, sewage sage and wastewater wizard.

There are two places I'm aware of where JN.1 is the dominant lineage, Limerick, Ireland and Iceland.
Both locations had recent news reports about their ERs being flooded.
This doesn't mean that JN.1 is more pathogenic, but it's got my attention.

https://www.mbl.is/frettir/innlent/2023/11/11/mikid_alag_a_bradamottokunni_i_fos...
{Icelandic?}

Some good news? While 18% experience LC and it lasts up to 1y, LC does not seem to be due to reactivation of Epstein-Barr Virus--in asymptomatic/mild COVID patients, at least.

Alexandra Domnica Hoeggerl et al. 2023. Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course. BMC Infectious Diseases volume 23, Article number: 800 (15 Nov 2023). Open access. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08820-w

Abstract
Purpose. ... Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS...

Results. Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.

Conclusion. Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.

YAY! 1-2 cups coffeeevery six hours , though?? (At least decaf works!)

Coffee and COVID: Study finds coffee inhibits SARS-CoV-2, offers new dietary defense strategy
Tarun Sai Lomte | Nov 16 2023

https://www.news-medical.net/news/20231116/Coffee-and-COVID-Study-finds-coffee-i...
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Wu CS, et al. 2023. Coffee as a dietary strategy to prevent SARS-CoV-2 infection. Cell Biosci, 14 Nov 2023, DOI: 10.1186/s13578-023-01154-9, https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01154-9

ABSTRACT
...Results
Here, we identified that coffee can inhibit multiple variants of the SARS-CoV-2 infection by restraining the binding of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), and reducing transmembrane serine protease 2 (TMPRSS2) and cathepsin L (CTSL) activity. Then, we used the method of "Here" (HRMS-exploring-recombination-examining) and found that isochlorogenic acid A, B, and C of coffee ingredients showed their potential to inhibit SARS-CoV-2 infection (inhibitory efficiency 43–54%). In addition, decaffeinated coffee still preserves inhibitory activity against SARS-CoV-2. Finally, in a human trial of 64 subjects, we identified that coffee consumption (approximately 1–2 cups/day) is sufficient to inhibit infection of multiple variants of SARS-CoV-2 entry, suggesting coffee could be a dietary strategy to prevent SARS-CoV2 infection.

...DISCUSSION
...we showed that the best timeline for impeding SARS-CoV-2 entry is within 6 h. after drinking coffee. It is recommended to intake coffee once again after 6 h. to maintain the efficacy of inhibiting SARS-CoV-2 infection.

Summary thread of the oral-vascular-pulmonary model of #COVID-19 lung disease, why this is important and what to do about it.
Also potentially relevant in #LongCOVID

- Dr Graham Lloyd-Jones @DrGrahamLJ | 11:53 AM · Nov 17, 2023:
Consultant Radiologist. Medical imaging educator: Director of Radiology Masterclass. Linking poor #oralhealth to systemic diseases #COVID #longCOVID.
21 tweets
https://twitter.com/DrGrahamLJ/status/1725557784752619633
https://threadreaderapp.com/thread/1725557784752619633.html
...
16/21
Why is this so important?
It means that it makes sense to care for your mouth if you have #COVID
Here is the mouth care guidance we offer our #COVID-19 patients @SalisburyNHS UK. It includes provision of an antiviral mouthwash against #SARS2
Salisbury Hospital COVID-19 Mouth Care Guidance ( https://patientinfo.microguide.global/SALIS/PIL1#content,1f6fad6a-c374-4517-9c58... )
Mouthcare infographic ( https://twitter.com/DrGrahamLJ/status/1725557821394104370/photo/1 )

7/21
Based on evidence that specific mouthwash ingredients eradicate #SARS2 in vitro and make it undetectable in the mouth for a prolonged period
See this systematic review of CPC mouthwash I wrote with Italian colleagues @DrFDamico
/@MMarmiere et al
Efficacy of Cetylpyridinium Chloride mouthwash against SARS-CoV-2: A systematic review of randomized controlled trials, 2023 ( https://onlinelibrary.wiley.com/doi/full/10.1111/omi.12408 )

18/21
And evidence that use of mouthwash in the setting of acute COVID-19 reduces intensive care admission and mortality!
See this research paper published in Nature {2021}
Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: randomised trial ( https://www.nature.com/articles/s41598-021-99013-5 )
...
21/21
Here's my brief summary of how to care for the mouth
1 - Stop smoking/vaping
2 - Stop eating free sugar in all its forms (sugary/fruit drinks, cake, sweets)
3 - Learn how to brush your teeth properly
4 - Visit the dentist/hygienist preventatively (before things go wrong)
--------------------------------------------------

G. Lloyd-Jones et al. 2023. The Oral-Vascular-Pulmonary Infection Route: a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19 (Review). Current Oral Health Reports. Open access. Published: 03 November 2023. https://link.springer.com/article/10.1007/s40496-023-00354-z#Sec18

ABSTRACT
...Summary
High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation...

...Oral Immune Barrier, Periodontitis, and Acute COVID-19
The oral mucosa is an immune defence barrier, providing physical and antimicrobial protection in healthy individuals through the beneficial effects of a health-promoting oral microbiome. Oral pathogens or toxins can more readily enter the body via the bloodstream when this barrier is compromised.... Simple actions like toothbrushing can result in transient bacteraemia in those with a healthy mouth ..., or even chewing in those with periodontitis .... Therefore, high titres of SARS-CoV-2 in a healthy mouth could result in viral entry into the bloodstream and to a greater degree in those with periodontal disease.

Periodontitis is strongly associated with chronic inflammatory diseases, such as type-2 diabetes mellitus, atherogenic cardiovascular disease, chronic kidney disease, inflammatory lung diseases, cognitive decline, and rheumatoid arthritis...

...Conclusion
The proposed disease model of the oral cavity as a SARS-CoV-2 reservoir combined with a breach of the oral mucosal immune barrier facilitating vascular viral delivery to the lungs and body remains compelling. Thus, the mouth can act as a mediator for disease severity via intravascular viral translocation. This oral-vascular-pulmonary infection route provides an anatomical model for the dominant vascular pathological mechanisms characteristic of the acute-phase COVID-19 lung disease and a potential model for long COVID. Detailed studies are required to enhance evidence for this pathway and to determine the role of oral hygiene measures and periodontal therapy, particularly in the context of long COVID.

Vitamin D supplementation reduced the rates of ICU admissions and mechanical ventilation associated with SARS-CoV-2 Infection
Physician's Weekly | Nov 18, 2023

1. In this meta-analysis, vitamin D supplementation was associated with reduced ICU admission and mechanical ventilation rates in patients with SARS-CoV-2 infection.

2. However, vitamin D supplementation did not significantly affect mortality associated with SARS-CoV-2 infection.

Evidence Rating Level: 1 (Excellent)...

https://www.physiciansweekly.com/vitamin-d-supplementation-reduced-the-rates-of-...
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Jiahao Meng etal. 2023. The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials. Clinical Nutrition, Volume 42, ISSUE 11, P2198-2206, November 2023. Open Access. DOI:https://doi.org/10.1016/j.clnu.2023.09.008 https://www.clinicalnutritionjournal.com/article/S0261-5614(23)00296-0/fulltext

Summary
...Results
We retrieved 25 eligible trials, including 8128 participants. Four trials compared the preventive effects of vitamin D supplementation on SARS-CoV-2 infection, and the results (RR {relative risk} 0.31) were inconclusive. Regarding the treatment of SARS-CoV-2 infection with vitamin D supplementation, it was found that vitamin D supplementation could significantly reduce the rates of ICU admission (RR 0.63...) and mechanical ventilation (RR 0.58...), but had no statistically significant effect on mortality. However, in subgroup analyses based on the patients' specific conditions, vitamin D supplementation significantly reduced the mortality in patients with vitamin D deficiency (RR 0.76...).

Conclusion
Vitamin D supplementation may have some beneficial impact on the severity of illness caused by SARS-CoV-2, particularly in VitD deficient patients, but further studies are still needed.

>149 margd: On a side note: Here in Denmark they concluded that blood tests for vitamin D were not needed since we all lack vitamin D when the sun starts disappearing in the fall. So we should just take vitamin D and not go to the doctor first to waste their time on telling us :-)

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As of November 20, 2023, residential households in the U.S. are eligible for another order of #4 free at-home tests from USPS.com. Here's what you need to know about your order:

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