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Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis
Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis
The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (V˙˙O2) at maximum fat oxidation (g min−1) than the healthy controls (P 0.05). Moderation analysis indicated that muscle power output significantly influenced the relationship between LCS and reduced peak fat oxidation (interaction β = −0.105 [95% confidence interval −0.174; −0.036]; P = 0.026). Therefore, when muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study sample P = 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy controls.
·clinicalnutritionespen.com·
Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis
TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by TMPRSS2 cleavage of ACE2
TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by TMPRSS2 cleavage of ACE2
Continued high-level spread of SARS-CoV-2 has enabled an accumulation of changes within the Spike glycoprotein, leading to resistance to neutralising antibodies and concomitant changes to entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) dependent entry by primary SARS-CoV-2 isolates that occurred upon arrival of Omicron lineages. Mechanistically we show this shift to be a function of two distinct ACE2 pools based on cleavage by TMPRSS2. In engineered cells overexpressing ACE2 and TMPRSS2, ACE2 cleavage by TMPRSS2 led to either augmentation or attenuation of viral infectivity of pre-Omicron and Omicron lineages, respectively. Mutagenesis of the TMPRSS2 cleavage site in ACE2 restored infectivity across all Omicron lineages through enabling ACE2 binding that facilitated TMPRSS2 activation of viral fusion. Our data supports the evolution of Omicron lineages towards the use of pools of ACE2 with the latter consistent with its role as a chaperone for many tissue specific amino acid transport proteins. ![Figure][1] Graphical Abstract: Cleaved ACE2 pool model and evolution of SARS-CoV-2 tropism. A. &-B. ACE2 cleaved pool model to reconcile the evolving entry requirements of SARS-CoV-2 and changes in viral tropism in vivo . A. Both SARS-CoV-1 and early SARS-CoV-2 (pre-Omicron) lineages undergo cleavage of ACE2 (blue protein) by TMPRSS2 (green protein) which promotes viral entry. In other settings in which ACE2 is not cleaved by TMPRSS2, viral entry still proceeds. Therefore, regardless of the cleavage state of ACE2, TMPRSS2 cleavage and activation of Spike S2 can proceed (“on” conformation) in pre-Omicron variants. B. For Omicron lineages, cleavage of ACE2 by TMPRSS2 does not lead to TMPRSS2 Spike S2 activation (“off” confirmation”). Whilst this supports attenuation in tissue where ACE2 is cleavage sensitive due to its role in soluble ACE2 regulation (e.g. lung), replication in other tissues proceeds. Independent of RAS, ACE2 can also act as a chaperone for several tissue-specific amino acid transporters which engage at and around the TMPRSS2 cleavage site, thus blocking the ACE2 cleavage site from TMPRSS2. To mimic the lack of ACE2 cleavage in this setting, we mutated the TMPRSS2 cleavage site in ACE2 and demonstrated that Omicron viral infection and TMPRSS2 Spike S2 activation can occur in the presence of non-cleaved ACE2 (“on” conformation). C. Cleaved (black dashed line) versus non-cleaved ACE2 (blue line) usage by SARS-CoV-2 variants throughout the pandemic. The appearance of globally dominant variants over time is presented as a backdrop (Nextstrain). Here, e arly SARS-CoV-2 lineages are observed to be augmented by the action of ACE2/TMPRSS2 cleavage. This augmentation steadily declines and crosses over to attenuation upon the arrival of the first Omicron lineage BA.1. Further attenuation is then observed with the appearance of the recombinant lineages such as O micron XBB and XBF. Concurrently, ACE2 resistant to TMPRSS2 cleavage has supported TMPRSS2 Spike S2 activation entry across all SARS-CoV-2 lineages equally. ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes
·biorxiv.org·
TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by TMPRSS2 cleavage of ACE2
SARS-CoV-2 infection and persistence throughout the human body and brain
SARS-CoV-2 infection and persistence throughout the human body and brain
COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with68 prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple pulmonary and extrapulmonary tissues early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our80 data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.
·assets.researchsquare.com·
SARS-CoV-2 infection and persistence throughout the human body and brain
Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets | American Journal of Physiology-Heart and Circulatory Physiology
Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets | American Journal of Physiology-Heart and Circulatory Physiology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection damages the heart, increasing the risk of adverse cardiovascular events. Female sex protects against complications of infection; females are less likely to experience severe illness or death, although their risk for postacute sequelae of COVID-19 (“long COVID”) is higher than in males. Despite the important role of the heart in COVID-19 outcomes, molecular elements in the heart impacted by SARS-CoV-2 are poorly understood. Similarly, the role sex has on the myocardial effects of SARS-CoV-2 infection has not been investigated at a molecular level. We intranasally inoculated female and male ferrets with SARS-CoV-2 and assessed myocardial stress signals, inflammation, and the innate immune response for 14 days. Myocardial phosphorylated GSK3α/β decreased at day 2 postinfection (pi) in male ferrets, whereas females showed no changes. Myocardial levels of p62/SQSTM1 decreased in male ferrets at days 2, 7, and 14 pi while lower baseline levels in females increased on day 2. Phosphorylated ERK1/2 increased in cardiomyocyte nuclei in females on days 2 and 14 pi, whereas male ferrets had no changes. Only hearts from females increased fibrosis on day 14 pi. Immune and inflammation markers increased in hearts, with some sex differences. These results are the first to identify myocardial stress responses following SARS-CoV-2 infection and reveal sex differences that may contribute to differential outcomes. Future research is required to define the pathways involving these stress signals to fully understand the myocardial effects of COVID-19 and identify targets that mitigate cardiac injury following SARS-CoV-2 infection. NEW & NOTEWORTHY Cardiovascular disease is a leading risk factor for severe COVID-19, and cardiovascular pathologies are among the most common adverse outcomes following SARS-CoV-2 infection. Females and males have different outcomes and adverse cardiovascular events following SARS-CoV-2 infection. This study shows sex differences in stress proteins p62/SQSTM1, ERK1/2, and GSK3α/β, along with innate immunity and inflammation in hearts of ferrets infected with SARS-CoV-2, identifying mechanisms of COVID-19 cardiac injury and cardiac complications of long COVID.
·journals.physiology.org·
Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets | American Journal of Physiology-Heart and Circulatory Physiology
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Importance/Background: The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients.Methods: We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin.Results: We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56–0.78; I2 = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53–1.00; I2 = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77–1.16; I2 = 0.0% for intubation and OR, 2.04; 95% CI, 0.65–6.34; I...
·frontiersin.org·
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Ambulante Metformin-Gabe in Akutphase senkt Long-COVID-Inzidenz
Ambulante Metformin-Gabe in Akutphase senkt Long-COVID-Inzidenz
Eine randomisiert-kontrollierte US-Studie zeigt, dass Metformin bei ambulant behandelten übergewichtigen und adipösen SARS-CoV-2-Infizierten offenbar vor der späteren Entwicklung von Long-COVID schützen kann. Wurde eine Metformin-Therapie innerhalb von drei Tagen nach Beginn der Akuterkrankung begonnen, sank das Risiko für Langzeitsymptome um 63 %.
·dgn.org·
Ambulante Metformin-Gabe in Akutphase senkt Long-COVID-Inzidenz
The Sato Lab (Kei Sato) on Twitter / X
The Sato Lab (Kei Sato) on Twitter / X
Altogether, these results suggest that a single dose of XBB.1.5 monovalent vaccine may not be sufficient to induce effective antiviral humoral immunity in infection-naïve individuals and that a booster dose of XBB.1.5 monovalent vaccine may be required in some cases. 9/— The Sato Lab (Kei Sato) (@SystemsVirology) November 30, 2023
·twitter.com·
The Sato Lab (Kei Sato) on Twitter / X
Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization
Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization
Introduction A chronic post-vaccination syndrome (PVS) after covid-19 vaccination has been reported but has yet to be well characterized. Methods We included 241 individuals aged 18 and older who self-reported PVS after covid-19 vaccination and who joined the online Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study from May 2022 to July 2023. We summarized their demographics, health status, symptoms, treatments tried, and overall experience. Results The median age of participants was 46 years (interquartile range [IQR]: 38 to 56), with 192 (80%) identifying as female, 209 (87%) as non-Hispanic White, and 211 (88%) from the United States. Among these participants with PVS, 127 (55%) had received the BNT162b2 [Pfizer-BioNTech] vaccine, and 86 (37%) received the mRNA-1273 [Moderna] vaccine. The median time from the day of index vaccination to symptom onset was three days (IQR: 1 day to 8 days). The time from vaccination to symptom survey completion was 595 days (IQR: 417 to 661 days). The median Euro-QoL visual analogue scale score was 50 (IQR: 39 to 70). The five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%). In the week before survey completion, participants reported feeling unease (93%), fearfulness (82%), and overwhelmed by worries (81%), as well as feelings of helplessness (80%), anxiety (76%), depression (76%), hopelessness (72%), and worthlessness (49%) at least once. Participants reported a median of 20 (IQR: 13 to 30) interventions to treat their condition. Conclusions In this study, individuals who reported PVS after covid-19 vaccination had low health status, high symptom burden, and high psychosocial stress despite trying many treatments. There is a need for continued investigation to understand and treat this condition. ### Competing Interest Statement Harlan Krumholz received expenses and/or personal fees from Element Science, Eyedentify, and F-Prime in the past three years. He is a co-founder of Refactor Health and Ensight-AI. He and his spouse are co-founders of, and have equity in, Hugo Health, the personalized health data platform company that developed the Hugo Kindred platform. His spouse is an officer with Hugo Health. The Yale Conflict of Interest Committee oversees his involvement in this study. He is the editor of Journal Watch: Cardiology of the Massachusetts Medical Society and a section editor for UpToDate. He is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services, and through Yale University from Janssen, Johnson & Johnson Consumer, and Pfizer. Akiko Iwasaki co-founded RIGImmune, Xanadu Bio, and PanV, consults for Paratus Sciences and InvisiShield Technologies, and is a member of the Board of Directors of Roche Holding Ltd. Yuan Lu received research grants from the United States National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Sentara Research Foundation outside of the submitted work. Jeph Herrin receives funding from multiple institutes of the National Institutes of Health, from the Patient-Centered Outcomes Research Institute, the American Heart Association, and the Agency for Healthcare Research and Quality for research projects; from the Centers for Medicare & Medicaid Services for development of quality measures; and from Pfizer. Chenxi Huang receives K12 funding from the National Center for Advancing Translational Science of the National Institutes of Health (UL1TR001863). Bornali Bhattacharjee is supported by, and Cesar Caraballo was supported by, a grant from the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). The other authors have no financial relationships to disclose. ### Funding Statement This project was in part supported by the Howard Hughes Medical Institute Collaborative COVID-19 Initiative and in part supported by CTSA Grant Number UL1 TR001863 from the National Center for Advancing Translational Science, a component of the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. ### 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 Yale University Institutional Review Board gave ethical approval to the LISTEN (Listen to Immune, Symptom and Treatment Experiences Now) study. STROBE reporting guidelines were followed. Harlan Krumholz, a co-founder of Hugo Health, developed the Hugo Kindred platform, and the Yale Conflict of Interest Committee oversees his involvement. 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 Deidentified data in the present study are available upon reasonable request to the authors.
·medrxiv.org·
Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans
Immune imprinting - also known as ‘original antigenic sin’ - describes how the first exposure to a virus shapes the immunological outcome of subsequent exposures to antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown to primarily recall cross-reactive memory B cells and antibodies induced by prior mRNA vaccination with the Wuhan-Hu-1 spike rather than priming naive B cells that recognize Omicron-specific epitopes. These findings underscored a strong immune imprinting resulting from repeated Wuhan-Hu-1 spike exposures. To understand if immune imprinting can be overcome, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID mRNA vaccine booster. Our data show that the XBB.1.5 booster elicits neutralizing antibody responses against current variants that are dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. These results indicate that immune imprinting persists even after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 spike booster mRNA vaccination, which will need to be considered to guide the design of future vaccine boosters. ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans
Excess mortality in England post Covid-19 pandemic: implications for secondary prevention
Excess mortality in England post Covid-19 pandemic: implications for secondary prevention
Many countries, including the UK, have continued to experience an apparent excess of deaths long after the peaks associated with the COVID-19 pandemic in 2020 and 2021.1,2 Numbers of excess deaths estimated in this period are considerable. The UK Office for National Statistics (ONS) has calculated that there were 7.2% or 44,255 more deaths registered in the UK in 2022 based on comparison with the five-year average (excluding 2020).1 This persisted into 2023 with 8.6% or 28,024 more deaths registered in the first six months of the year than expected.
·thelancet.com·
Excess mortality in England post Covid-19 pandemic: implications for secondary prevention
Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naïve individuals independently of their antibody affinity
Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naïve individuals independently of their antibody affinity
Memory B cells (MBCs) formed over the individual’s lifetime constitute nearly half of the adult peripheral blood B cell repertoire in humans. To assess their response to novel antigens, we tracked the origin and followed the differentiation paths of MBCs in the early anti-S response to mRNA vaccination in SARS-CoV-2-naïve individuals on single-cell and monoclonal antibody level. Newly generated and pre-existing MBCs differed in their differentiation paths despite similar levels of SARS-CoV-2 and common corona virus S-reactivity. Pre-existing highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody secreting cells (ASCs). In contrast, newly generated MBCs derived from naïve precursors showed strong signs of antibody affinity maturation before differentiating into ASCs. Thus, although pre-existing human MBCs have an intrinsic propensity to differentiate into ASCs, the quality of the anti-S antibody and MBC response improved through the clonal selection and affinity maturation of naïve precursors. Highlights ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naïve individuals independently of their antibody affinity
Long COVID is associated with severe cognitive slowing
Long COVID is associated with severe cognitive slowing
Background COVID-19 survivors may suffer from a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods To examine cognitive slowing, PCC patients completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). Findings We identified pronounced cognitive slowing in PCC patients, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-second task measuring simple reaction time (SRT), with PCC patients responding to stimuli ~3 standard deviations slower than healthy controls. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in PCC patients. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of PCC patients on the NVT measure of sustained attention. Interpretation Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in PCC patients. Funding Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thuringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by funding from the Wellcome Trust, NIHR Oxford Health Biomedical Research Centre, and the Thuringer Aufbaubank (2021 FGI 0060). S.Z. and M.H. were funded by the Wellcome Trust (206330/Z/17/Z). E.M.M. was funded by Ph.D. scholarship Landesgraduiertenstipendium of Friedrich-Schiller-University Jena. K.F. was funded by German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890). ### 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 ethics committee of Jena University Hospital (Approval Reference: 5082-02/17) and South Central Oxford A Research Ethics Committee (Approval Reference: 18/SC/0448) 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 De-identified data supporting this study may be shared based on reasonable written requests to the corresponding author. Access to de-identified data will require a Data Access Agreement and IRB clearance, which will be considered by the institutions who provided the data for this research. The simple reaction time task and the number vigilance task can be tried online at [https://octalportal.com/pcc]. The source code is shared using a Creative Commons NC-ND 4.0 international licence upon reasonable written request to the corresponding author and publicly available at [https://octalportal.com/pcc].
·medrxiv.org·
Long COVID is associated with severe cognitive slowing
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants
COVID-19 vaccines have recently been updated with the spike protein of SARS-Co-V-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public. ### Competing Interest Statement D.D.H. co-founded TaiMed Biologics and RenBio, and he serves as a consultant for WuXi Biologics and Brii Biosciences and is a board director at Vicarious Surgical. A.G. served as a member of the scientific advisory board for Janssen Pharmaceuticals. The remaining authors declare no conflicts of interest.
·biorxiv.org·
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants
Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study
Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study
Objective To investigate the effectiveness of primary covid-19 vaccination (first two doses and first booster dose within the recommended schedule) against post-covid-19 condition (PCC). Design Population based cohort study. Setting Swedish Covid-19 Investigation for Future Insights—a Population Epidemiology Approach using Register Linkage (SCIFI-PEARL) project, a register based cohort study in Sweden. Participants All adults (≥18 years) with covid-19 first registered between 27 December 2020 and 9 February 2022 (n=589 722) in the two largest regions of Sweden. Individuals were followed from a first infection until death, emigration, vaccination, reinfection, a PCC diagnosis (ICD-10 diagnosis code U09.9), or end of follow-up (30 November 2022), whichever came first. Individuals who had received at least one dose of a covid-19 vaccine before infection were considered vaccinated. Main outcome measure The primary outcome was a clinical diagnosis of PCC. Vaccine effectiveness against PCC was estimated using Cox regressions adjusted for age, sex, comorbidities (diabetes and cardiovascular, respiratory, and psychiatric disease), number of healthcare contacts during 2019, socioeconomic factors, and dominant virus variant at time of infection. Results Of 299 692 vaccinated individuals with covid-19, 1201 (0.4%) had a diagnosis of PCC during follow-up, compared with 4118 (1.4%) of 290 030 unvaccinated individuals. Covid-19 vaccination with any number of doses before infection was associated with a reduced risk of PCC (adjusted hazard ratio 0.42, 95% confidence interval 0.38 to 0.46), with a vaccine effectiveness of 58%. Of the vaccinated individuals, 21 111 received one dose only, 205 650 received two doses, and 72 931 received three or more doses. Vaccine effectiveness against PCC for one dose, two doses, and three or more doses was 21%, 59%, and 73%, respectively. Conclusions The results of this study suggest a strong association between covid-19 vaccination before infection and reduced risk of receiving a diagnosis of PCC. The findings highlight the importance of primary vaccination against covid-19 to reduce the population burden of PCC.
·bmj.com·
Covid-19 vaccine effectiveness against post-covid-19 condition among 589 722 individuals in Sweden: population based cohort study
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
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
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.
·thelancet.com·
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