Covid19-Sources

This cohort study of electronic health care data of more than 8 million individuals in England attempts to quantify the neuropsychiatric sequelae following discharge from COVID-19 hospitalization compared with patients surviving hospitalization due to non–COVID-19 severe acute respiratory...

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 [SD 21·9]; 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 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. 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 [95% CI 0·94–1·10) or anxiety (1·00 [0·94–1·06]) 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 [1·09–1·33] to 2·16 [1·46–3·19]). 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.

Age-standardised mortality rates for deaths involving coronavirus (COVID-19), non-COVID-19 deaths and all deaths by vaccination status, broken down by age group.

SARS-CoV-2 Omicron sub-variants have generated a world-wide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron sub-variants and prepare for potential new variants, additional means of isolating broad and potent humanized SARS-CoV-2-neutralizing antibodies are desirable. Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human VH1-2 heavy chain (HC) and, substantially, a human Vκ1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact complementarity-region-3 (CDR3) sequences generated by non-templated junctional modifications during V(D)J recombination. Immunizing the human VH1-2/Vκ1-33-rearranging mouse model with SARS-CoV-2 (Wuhan-Hu-1) spike protein immunogens elicited several VH1-2/Vκ1-33-based neutralizing antibodies that bound RBD in a different mode from each other and from those of many prior human patient-derived VH1-2-based neutralizing antibodies. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 bound RBD away from the receptor-binding-motif via a CDR3-dominated recognition mode. Lattice-light-sheet-microscopy-based studies showed that SP1-77 did not block ACE2-mediated viral attachment or endocytosis, but rather blocked viral-host membrane fusion. The broad and potent SP1-77 neutralization activity and non-traditonal mechanism of action suggest this antibody might have therapeutic potential. Likewise, the SP1-77 binding epitope may further inform on vacccine strategies. Finally, the general class of humanized mouse models we have described may contribute to identifying therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.

New antibody neutralizes all known SARS-CoV-2 variants in lab tests

Im Jahr 2021 belief sich der durchschnittliche Krankenstand in der gesetzlichen Krankenversicherung auf rund 4,34 Prozent.

This cohort study estimates the proportion of persons who became reinfected with SARS-CoV-2 during the Omicron wave in Iceland.

Anhand von Daten der in der prä-Pandemie-Ära begonnenen, longitudinal angelegten „UK Biobank“ konnten erstmals zerebrale MRT-Befunde vor und nach COVID-19 bei denselben Personen erhoben und mit einer Kontrollgruppe Nicht-Infizierter verglichen werden [1]. Im Ergebnis zeigte sich bei den zwischenzeitlich SARS-CoV-2-Infizierten ein Rückgang an grauer Substanz im orbitofrontalen Kortex sowie eine Abnahme der Gesamthirnmasse. Bei den […]

Sehr guter Artikel - passt auf (nicht nur bei COVID), ob in einem Argument "orange Kreise", also absolute und nicht relative Fakten, vorkommen.Und passt noch mehr darauf auf, wie diese unverrückbaren Fakten durch "blaue Kreise" relativiert werden.⬇️⬇️https://t.co/KxKnlba9eo pic.twitter.com/XWoYJrgwAI— Michael (Mike) Meier (@AK_Meier) August 3, 2021

Die von etwa Dezember bis April dominanten Omikron-Varianten BA.1 und BA.2 des SARS-CoV-2-Virus können bereits nach drei Monaten den Schutz vor einer Infektion unterlaufen, den Impfungen oder überstandene Infektionen bieten. […]

Original Article from The New England Journal of Medicine — Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age

A string of negatives can still presage a clear-as-day positive.

Some friends and I are currently in an interesting covid predicament, which we're calling "phantom-covid", we don't know anyone who's had this experience and we can't find any precedent for it, but we're pretty desperate to figure out what's going on, so time to turn to twitter🧵 pic.twitter.com/EU5G3IZ8BI— Saoi O’Connor (@saoi4climate) August 14, 2022

The rise of BA.2.75 has been studied very carefully by @TWenseleers and its trajectory may vary considerably between countries. Or we could see a co-dominance pattern, something that hasn't occurred yet /9 pic.twitter.com/myYGLCDDGg— Eric Topol (@EricTopol) August 14, 2022

ONFH after COVID-19 can have a varied presentation. While the most common presentation is like classical ONFH, some patients can have an acute and aggressive presentation with rapid destruction. They have features like elevated serological markers and extensive periarticular bone and soft tissue ede …

Background. In February 2022, following the rescinding of a Massachusetts statewide school masking mandate, only two cities (Boston and neighboring Chelsea) out of 79 school districts in the greater-Boston area, maintained masking requirements in K-12 schools. This provided an opportunity to examine the impact of removing masking on COVID-19 case rates among students and staff in the public-school setting. Methods. We used difference-in-differences for staggered policy adoption to compare incidence of COVID-19 cases among students and staff in greater-Boston area school districts that lifted masking requirements to those that had not yet lifted masking requirements during the 2021-2022 school year. Results. Before the statewide school masking policy was lifted, there was no statistically significant difference in case rate trajectories between school districts. However, weekly and cumulative case rates were significantly higher in students and staff in school districts that removed masking requirements, compared to districts that had not yet lifted requirements. We estimate that lifting of school masking requirements was associated with an additional 44.9 (95% CI: 32.6, 57.1) COVID-19 cases per 1,000 students and staff over the 15 weeks since the lifting of the statewide school masking requirement, representing nearly 30% of all cases observed in schools during that time. School districts that sustained masking requirements for longer periods tended to have older school buildings in poorer condition, more crowded classrooms, higher proportion of low income and English learning students and students with disabilities, and a higher proportion of Black and Latinx students and staff. Conclusions. Masking is a relatively low-cost but effective intervention that can protect students and staff from substantial illness and loss of in-person days in school. Despite compelling evidence that masking significantly reduces the spread of SARS-CoV-2, political will and public adherence to masking has waned. Our study confirms that universal masking requirements can benefit all students and staff, and therefore represents an important strategy to mitigate the impacts of structural racism, ensure health equity, and to avoid potential deepening of educational inequities. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any external funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data utilized in this study are publicly available through the Massachusetts Department of Elementary and Secondary Education (https://www.doe.mass.edu/covid19/positive-cases/default.html#weekly-report); Massachusetts Department of Public Health (https://www.mass.gov/info-details/covid-19-response-reporting); and the Massachusetts School Building Authority (https://www.massschoolbuildings.org/programs/school_survey)

Background Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. [Clinicaltrials.gov][1] NCT05289037 ### Competing Interest Statement ARB has research grants from Pfizer, Janssen, Merck Sharp and Dohme and CyanVac and serves on the DSMB board for AzurX Biopharma and has served as a consultant for Janssen. ARF has research grants from Pfizer, Janssen, CyanVac, Merck Sharp and Dohme and BioFire Diagnostics and serves on the DSMB for Novavax. EW has research grants from Janssen, Merck Sharp and Dohme and Pfizer and served on a DSMB sponsored by GlaxoSmithKline. NGR has research grants from Pfizer, Sanofi Pasteur, Merck Sharp and serves on the Safety Monitoring Committees for ICON and EMMES. DSG receives consulting fees from Critica, Inc a non-profit organization. LRB has received grant support from NIH for SARS-CoV-2 therapeutic and vaccine development work and is involved in SARS-CoV-2 vaccine trials conducted in collaboration with the NIH, Covid Prevention Network (CoVPN), Crucell/Janssen, Moderna, and Harvard Medical School. SRW has conducted clinical trials funded by Sanofi Pasteur, Janssen Vaccines, ModernaTx, and NIAID/NIH and chairs an Independent Data Monitoring Committee (IDMC) for Janssen Vaccines. CMH is a member of a Safety Monitoring Committee for the Emmes Corporation. SJL has received research grant support to UCSD from Gilead Sciences. Her institution has also received funding from NIH to conduct clinical trials of Janssen and AstraZeneca COVID-19 vaccines. EJA has consulted for Pfizer, Sanofi Pasteur, Janssen, GSK, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on data and safety monitoring boards for Kentucky BioProcessing, Inc. and Sanofi Pasteur. He also serves on safety monitoring committees for WCG-ACI Clinical. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. The institution for SK has received funding from CDC to conduct clinical research unrelated to this manuscript, from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines, and from Pfizer to conduct clinical trials of Pfizer COVID-19 vaccine. The institution for CAR has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Novavax, PaxVax, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc. Her institution has received funds from NIH, Moderna, Pfizer, and Janssen to conduct clinical trials of COVID-19 vaccines. EBW has served as an investigator for vaccine studies sponsored by Pfizer, Moderna and Sequiris. He has served on advisory boards for Vaxcyte and Iliad Biotechnologies. MJS has served as an investigator for vaccine studies sponsored by Pfizer, and has received investigator-initiated grants from Merck related to antimicrobial stewardship. RMN has received research grant funding from ModernaTX, Inc and Janssen Vaccines & Prevention B.V. AW has received funding from NIH, GlaxoSmithKline and Sanofi and has been a consultant for Aicuris, X-Vax, Vir, Crozet, and Auritec. ACK reported clinical trials contract funding for vaccines or MAB vs SARS-CoV-2 with Regeneron and Pfizer. AFL has received research grant support to UCSF from Astra Zeneca. The Washington University Clinical Trials Unit has received unrelated funding support in sponsored research agreements from Moderna. PAG receives grant funding from the NIH and is a consultant for Johnson and Johnson. ### Clinical Trial NCT05289037 ### Funding Statement The trial was sponsored and funded by the National Institute of Allergy and Infectious Diseases. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was reviewed and approved by the Advarra central institutional review board which gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://Clinicaltrials.gov

Eine vollständige Entwarnung kann Leif Erik Sander für den nahenden Corona-Herbst nicht geben. Das sagt der Impfstoffforscher von der Berliner Charité im RND-Interview. Und erklärt, warum sich Jüngere nicht unbedingt ein viertes Mal gegen Covid-19 impfen lassen müssen.

Der Kinderpneumologe und -kardiologe Dr. Gerald Hofner erzählt im Interview, welche Herausforderungen die Pädiatrie meistern muss, wie er die Corona-Debatte zwischen „Kinderdurchseuchung“ und psychosozialen Folgen erlebt und wie es um die Zukunft von Kinder- und Jugendarztpraxen steht.

Mit den eigenen Waffen schlagen: Die Moleküle der hochansteckenden Omikron-Variante besitzen eine höhere Ladung – das lässt sich auch gegen das Coronavirus verwenden

🚨POST-COVID & Kids🚨New @CDCgov report showing quite clearly that children are at significantly more risk for life-threatening diagnoses after COVID infection. Very convincing evidence that prevention of COVID-19 in children is very important to reduce childhood mortality./1 pic.twitter.com/ntNs5CuQ6d— Tyler Black, MD (@tylerblack32) August 4, 2022

Kids, School, and Suicide=-=-=-=-=-=-=-=-People are asking about the stats I presented about school days being associated with child suicide. There are many ways to look at it.Simply, using July as a reference month, you can easily see "school peaks."It's very striking./1 pic.twitter.com/3CYslprNFP— Tyler Black, MD (@tylerblack32) July 1, 2022

Recently, we reported that BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs), yet less against the highly contagious Omicron sublineages BA.4 and BA.5 that have displaced previous variants. As the latter sublineages are derived from Omicron BA.2, we characterized serum neutralizing activity of COVID-19 mRNA vaccine triple-immunized individuals who experienced BA.2 breakthrough infection. We demonstrate that sera of these individuals have broadly neutralizing activity against previous VOCs as well as all tested Omicron sublineages, including BA.2 derived variants BA.2.12.1, BA.4/BA.5. Furthermore, applying antibody depletion we showed that neutralization of BA.2 and BA.4/BA.5 sublineages by BA.2 convalescent sera is driven to a significant extent by antibodies targeting the N-terminal domain (NTD) of the spike glycoprotein, whereas their neutralization by Omicron BA.1 convalescent sera depends exclusively on antibodies targeting the receptor binding domain (RBD). These findings suggest that exposure to Omicron BA.2, in contrast to BA.1 spike glycoprotein, triggers significant NTD specific recall responses in vaccinated individuals and thereby enhances the neutralization of BA.4/BA.5 sublineages. Given the current epidemiology with a predominance of BA.2 derived sublineages like BA.4/BA.5 and rapidly ongoing evolution, these findings are of high relevance for the development of Omicron adapted vaccines. ### Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE. A.M., B.G.L., K.K., A.W., M.B., A.F., A.T., and O.O. are employees at BioNTech SE. K.G., S.H. and S.C. are employees at University Hospital, Goethe University Frankfurt. U.G. is an employee at the Health Protection Authority, City of Frankfurt am Main. U.S., O.T. and A.M. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccines. U.S., O.T., A.M., B.G.L., K.K., A.W., M.B., A.F., A.T., and O.O. have securities from BioNTech SE. S.C. has received honorarium for serving on a clinical advisory board for BioNTech.

Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, that displays enhanced antibody escape properties. Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 16 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta and Omicron BA.1, BA.2, BA.5 variants in 291 sera and 35 nasal swabs from 27 individuals. Upon vaccination, serum Nab titers were reduced by 10-, 15-and 25-fold for BA.1, BA.2 and BA.5, respectively, compared with D614G. The duration of neutralization was markedly shortened, from an estimated period of 11.5 months post-boost with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 4-5 months. In nasal swabs, infection, but not vaccination, triggered a strong IgA response and a detectable Omicron neutralizing activity. Thus, BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Work in OS lab is funded by: Institut Pasteur Urgence COVID-19 Fundraising Campaign of Institut Pasteur Fondation pour la Recherche Medicale (FRM) ANRS Vaccine Research Institute (ANR10LABX77) Labex IBEID (ANR10LABX62IBEID) ANR/FRM Flash Covid PROTEOSARSCoV2 ANR Coronamito and IDISCOVR. DP is supported by the Vaccine Research Institute. Work in OS lab is funded by: Institut Pasteur INCEPTION program (Investissements Avenir grant ANR16CONV0005) The French Government Investissement Avenir programme Laboratoire Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR10LABX62IBEID) NIH PICREID (grant no U01AI151758). The Opera system was cofunded by Institut Pasteur and the Region ile de France (DIM1Health). Work in UPBI is funded by: grant ANR10INSB0401 Region Ile de France program DIM1 Health. The funders of this study had no role in study design data collection and analysis and interpretation or writing of the article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study [NCT04750720][1] was approved by the Ile de France IV ethical committee. At enrollment, written informed consent was collected and participants completed a questionnaire covering sociodemographic characteristics, virological findings (SARSCoV2 RTqPCR results, date of testing) and data related to SARSCoV2 vaccination (brand product, date of first, second and third vaccination). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the corresponding authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04750720&atom=%2Fmedrxiv%2Fearly%2F2022%2F07%2F22%2F2022.07.22.22277885.atom

Nature Medicine - A retrospective analysis of primary care records in the United Kingdom reveals individual symptoms associated with SARS-CoV-2 infections, which persisted for 12 weeks or more...

Nature Biotechnology - Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC. ### Competing Interest Statement David Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company and also serves on its Board of Directors. Dr. Walt's interests were reviewed and are managed by Brigham and Women's Hospital and Partners Healthcare in accordance with their conflict of interest policies. ### Funding Statement This study was funded by the Hostetter Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Massachusetts General Brigham Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon request to the authors.

The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of 80,000 virus-reactive CD8+ T cells, obtained using a modified antigen-reactive T cell enrichment assay, from 39 patients with COVID-19 and 10 healthy participants. Patients with COVID-19 were segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was “exhausted” or “non-exhausted.” SARS-CoV-2–reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in patients with COVID-19 experiencing mild compared with severe illness. In contrast, SARS-CoV-2–reactive cells in the dominant nonexhausted subset from patients with severe disease showed enrichment of transcripts linked to costimulation, prosurvival NF-κB signaling, and antiapoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy participants displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2–reactive cells from both patients with COVID-19 and healthy controls nonexposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.

This evidence brief includes evidence that has emerged since the previous Public Health Ontario (PHO) BA.4 and BA.5 Evidence and Risk Assessment. 1