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Different roads, same destination: Study shows COVID variants evolve to suppress immunity
Different roads, same destination: Study shows COVID variants evolve to suppress immunity
The spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19, has basked in the spotlight since the pandemic began. | In the world of COVID variants, many mutations seem to lead to the same goal: Evade innate immunity. By pinpointing key proteins that make this "convergent evolution" possible, researchers are on the way to finding new targets for therapies.
·fiercebiotech.com·
Different roads, same destination: Study shows COVID variants evolve to suppress immunity
Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections
Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections
Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers of de novo responses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on these de novo responses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naïve B cells. We conclude that dampened de novo B cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance. ### Competing Interest Statement Sana Biotechnology has licensed intellectual property of D.B. and Washington University in St. Louis. Gilead Sciences has licensed intellectual property of D.B. and Stanford University. Clade Therapeutics has licensed intellectual property of D.B. and University of Arizona. D.B. is a co-founder of Clade Therapeutics. D.B. served on an advisory panel for GlaxoSmithKline. B.J.L. has a financial interest in Cofactor Genomics, Inc. and Iron Horse Dx. Geneticure Inc. has licensed intellectual property of R.S. and R.S is a co-founder of Geneticure Inc. M.W. has received consulting fees from GLG on SARS-CoV-2 and the COVID-19 pandemic. ### Funding Statement This work was supported by NIH grants R01AI099108 and R01AI129945 (D.B.) and a research grant from the Arizona Board of Regents (M.W. and D.B). This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00015 (M.W.) The HEROES-RECOVER cohort is supported by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention (contracts 75D30120R68013 to Marshfield Clinic Research Institute, 75D30120C08379 to the University of Arizona, and 75D30120C08150 to Abt Associates). ### 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: IRB of The University of Arizona 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors
·medrxiv.org·
Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections
Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses
Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses
Long-COVID, also known as post-COVID-19 conditions (PCC), has emerged as the next public health crisis with an estimated incidence of 10-30% in non-hospitalized and 50-70% in hospitalized individuals [1]. PCC is clinically heterogeneous, having been associated with over 200 symptoms [2]. In October 2021, the World Health Organization (WHO) defined PCC as ε1 symptom not explained by an alternate diagnosis, lasting at least 2 months, in individuals with probable or confirmed SARS-CoV-2 infection, 12 weeks from the onset of illness [3].
·ijidonline.com·
Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses
COVID-19 patients retain elevated risk of death for at least 18 months after infection
COVID-19 patients retain elevated risk of death for at least 18 months after infection
COVID-19 is associated with higher risks of cardiovascular disease and death in the short- and long-term, according to a study in nearly 160,000 participants published today in Cardiovascular Research, a journal of the European Society of Cardiology (ESC).1 Compared to uninfected individuals, the likelihood of COVID-19 patients dying was up to 81 times higher in the first three weeks of infection and remained five times higher up to 18 months later.
·eurekalert.org·
COVID-19 patients retain elevated risk of death for at least 18 months after infection
Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant
Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant
In September, 2023, the SARS-CoV-2 XBB descendants, such as XBB.1.5 and EG.5.1 (originally XBB.1.9.2.5.1), are the predominant variants circulating worldwide.1 Unexpectedly, however, a lineage distinct from XBB was identified and named BA.2.86 on Aug 14, 2023.2 Notably, BA.2.86 bears more than 30 mutations in the spike (S) protein when compared with XBB and the parental BA.2, and many of these mutations are assumed to be associated with immune evasion (appendix p 10).2 Although the number of reported cases is low (68 sequences have been reported as of Sept 7, 2023), BA.2.86 has been detected in several continents (Europe, North America, and Africa), suggesting that this variant might be spreading silently worldwide.
·thelancet.com·
Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant
Differences of Disabling Symptoms between Previously Hospitalized or Non-Hospitalized Currently Working Long-COVID Survivors One Year after Infection: A Descriptive Study
Differences of Disabling Symptoms between Previously Hospitalized or Non-Hospitalized Currently Working Long-COVID Survivors One Year after Infection: A Descriptive Study
This study aimed to describe the presence of disabling symptoms in currently working Long-COVID survivors by comparing the hospitalized and non-hospitalized one year after infection. Patients with Long-COVID syndrome (LCS) that have been infected by COVID-19 a year ago and were actually working were included. Participants that had been hospitalized due to COVID-19 were included in the LCS hospitalized group, and participants that had not been hospitalized were included in the LCS non-hospitalized group. The eligible patients were prompted to complete the latest self-report version of the COVID-19 Yorkshire Rehabilitation Screening Tool (C19-YRS). A total of 465 subjects were included in the study. Participants in the LCS hospitalized group were significantly older, had a significantly higher BMI, and had a significantly higher prevalence of women compared to the LCS non-hospitalized group. Additionally, participants in the LCS hospitalized group had obtained significantly worse results in symptom severity, functional disability, and global health perceived subscales of C19-YRS compared to the participants included in the LCS non-hospitalized group. We concluded that disabling symptoms are presented in patients with LCS at working age one year after infection and are higher in LCS hospitalized patients compared to LCS non-hospitalized patients.
·mdpi.com·
Differences of Disabling Symptoms between Previously Hospitalized or Non-Hospitalized Currently Working Long-COVID Survivors One Year after Infection: A Descriptive Study
Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines
Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines
Background Subvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. Methods In this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-µg doses of mRNA-1273.815 monovalent (50-µg omicron XBB.1.5 spike mRNA) or mRNA-1273.231 bivalent (25-µg omicron XBB.1.5 and 25-µg omicron BA.4/BA.5 spike mRNAs) vaccines, administered as 5th doses, to adults who previously received a primary series and 3rd dose of an original mRNA coronavirus disease 2019 (Covid-19) vaccine, and a 4th dose of a bivalent (omicron BA.4/BA.5 and original SARS-CoV-2) vaccine. Interim safety and immunogenicity data 15 days post-vaccination are presented. Results In April 2023, participants received mRNA-1273.815 (n=50) and mRNA-1273.231 (n=51). The median intervals from the prior dose of BA.4/BA.5-containing bivalent vaccine were 8.2 and 8.3 months for the mRNA-1273.815 and mRNA-1273.231 groups, respectively. Both vaccines increased neutralizing antibody (nAb) geometric mean titers against all variants tested at day 15 post-booster nAb compared to pre-booster levels. Geometric mean fold-rises from pre-booster titers after the monovalent booster were numerically higher against XBB.1.5, XBB.1.16 and SARS-CoV-2 (D614G) than those of the bivalent booster and were comparable against BA.4/BA.5 and BQ1.1 variants for both vaccines. The monovalent vaccine also elicited nAb responses against omicron XBB.2.3.2, EG.5.1, FL.1.5.1 and BA.2.86 that were similar to those against XBB.1.5 in a subset (n=20) of participants. The occurrence of solicited adverse reactions and unsolicited adverse events were overall similar to those previously reported for the original mRNA-1273 50-µg and omicron BA.4/BA.5-containing bivalent mRNA-1273 vaccines. Conclusion In this interim analysis, XBB.1.5-containing monovalent and bivalent vaccines elicited potent neutralizing responses against variants of the omicron XBB-lineage (XBB.1.5, XBB.1.6, XBB.2.3.2, EG.5.1, and FL.1.5.1) as well as the recently emerged BA.2.86 variant. The safety profile of the XBB.1.5-containing vaccine was consistent with those of prior vaccines. These results overall indicate that the XBB.1.5-containing mRNA-1273.815 vaccine has the potential to provide protection against these emerging variants and support the Covid-19 vaccine update in 2023-2024 to a monovalent XBB.1.5-containing vaccine. ### Competing Interest Statement JW, BE, and AB have nothing to disclose; DCM reports funding from Moderna, Inc. for pseudovirus neutralization assays performed in the study; LRB is a co-primary principal investigator of the COVE trial funded by NIAID and conducted in conjunction with Moderna, Inc. SC, NMcG, BG, KW, DKE, AN, DL, LEA, JF, WD, JMM and RD are employees of Moderna, Inc. and may hold stock/stock options in the company. JET is a Moderna consultant. ### Clinical Trial NCT04927065 ### Funding Statement This study was funded by Moderna, Inc., Cambridge, Massachusetts, USA. ### 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 central Institutional Review Board (Advarra, Inc., 6100 Merriweather Drive, Columbia, MD 21044) approved the protocol and consent forms. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes As the trial is ongoing, access to patient-level data and supporting clinical documents with qualified external researchers may be available upon request and subject to review once the trial is complete.
·medrxiv.org·
Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines
Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes
Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes

During the winter of 2022-2023, high rates of all-cause mortality, not seen since April 2020, were recorded in France, with excess all-cause mortality being related to the Omicron and influenza epidemics during that period. Moreover, that period saw a significant increase in the proportion of residents in long-term care facilities among cases of death in the population. Studies have found that increased influenza vaccination coverage in healthcare workers can result in a substantial reduction (up to 20%-30% during the course of select influenza seasons in the pre-pandemic period) in all-cause mortality in residents in nursing homes. Methods: We applied the previously developed methodology to estimate the contribution of influenza infections to all-cause mortality in France for the 2014-2015 through the 2018-2019 influenza seasons, and the contribution of both SARS-CoV-2 and influenza infections to all- cause mortality between week 33, 2022 through week 12, 2023. Results: For the 2014-2015 through the 2018-2019 seasons, influenza was associated with an average of 15654 (95% CI (13013,18340)) deaths, while between week 33, 2022 through week 12, 2023, we estimated 7851 (5213,10463) influenza-associated deaths and 32607 (20794,44496) SARS-CoV-2 associated deaths. The number of SARS-CoV-2-associated deaths during the Omicron epidemic was significantly higher than the number of deaths with COVID-19 listed on the death certificate or the hospitalization record – for example, between weeks 33-52 in 2022, we estimated 23983 (15307,32620) SARS-CoV-2-associated deaths in France, compared with 12811 deaths with COVID-19 listed on the death certificate, and 8639 in-hospital deaths with COVID-19 during the .CC-BY-NC 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)

NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. same period. Examination of US mortality data suggests a significant contribution of Omicron infections to mortality for cardiac disease and mental/behavioral disorders with COVID-19 not listed on the death certificate. Conclusions: Our results suggest the need for boosting influenza vaccination coverage in different population groups (including healthcare workers, particularly nurse assistants for whom influenza vaccination coverage rates in France are low), as well as for wider use of influenza antiviral medications in influenza-related respiratory hospitalizations with different diagnoses (including pneumonia). Wider detection and treatment of Omicron infections, particularly in older individuals/persons with underlying health conditions such as cardiac disease and mental/behavioral disorders, and wider use of bivalent COVID-19 boosters would be needed in the event of the recrudescence of Omicron circulation in France.

·medrxiv.org·
Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes
A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population
A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population
CONTEXT. Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain.OBJECTIVE. To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population.DATA SOURCES. PubMed, Embase, Web of Science,...
·publications.aap.org·
A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
Nature Communications - The authors characterize immune response in Omicron-infected vaccinated individuals and observe an immune enhancement. While increases in neutralizing antibodies and spike T...
·nature.com·
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron
SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron
We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373) cross-recognize early S…
·sciencedirect.com·
SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron