Covid19-Sources

The COVID‐19 pandemic has endured for over three years with over twelve variants afflicting humans worldwide. The impact and longevity of the pandemic has driven the medical community and researchers to identify high‐risk populations, yet few studies have explored temporal trends during the pandemic. The objective of this study is to investigate trends in all‐ cause mortality associated with co‐morbid cardiovascular disease (CVD) throughout the consecutive waves of the COVID‐19 pandemic.

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID ...

We should be rallied to defend ourselves and our kids. Our leaders offer timid silence.

With the aim of broadening immune responses against the evolving SARS-CoV-2 Omicron variants, bivalent COVID-19 mRNA vaccines that encode the ancestral and Omicron BA.5 spike proteins have been authorized for clinical use, supplanting the original monovalent counterpart in numerous countries. However, recent studies have demonstrated that administering either a monovalent or bivalent vaccine as a fourth vaccine dose results in similar neutralizing antibody titers against the latest Omicron subvariants, raising the possibility of immunological imprinting. Utilizing binding immunoassays, pseudotyped virus neutralization assays, and antigenic mapping, we investigated antibody responses from 72 participants who received three monovalent mRNA vaccine doses followed by either a bivalent or monovalent booster, or who experienced breakthrough infections with the BA.5 or BQ subvariant after vaccinations with an original monovalent vaccine. Compared to a monovalent booster, the bivalent booster did not yield noticeably higher binding titers to D614G, BA.5, and BQ.1.1 spike proteins, nor higher virus-neutralizing titers against SARS-CoV-2 variants including the predominant XBB.1.5 and the emergent XBB.1.16. However, sera from breakthrough infection cohorts neutralized Omicron subvariants significantly better. Multiple analyses of these results, including antigenic mapping, made clear that inclusion of the ancestral spike prevents the broadening of antibodies to the BA.5 component in the bivalent vaccine, thereby defeating its intended goal. Our findings suggest that the ancestral spike in the current bivalent COVID-19 vaccine is the cause of deep immunological imprinting. Its removal from future vaccine compositions is therefore strongly recommended. ### Competing Interest Statement The authors declare potential conflicts of interest as follows: D.D.H. is a co-founder of TaiMed Biologics and RenBio, as well as a board director for Vicarious Surgical; he also serves as a consultant to WuXi Biologics, Brii Biosciences, and Veru; and he receives research support from Regeneron. A.G. served on a scientific advisory board for Janssen Pharmaceuticals. The remaining authors declare no competing interests.

Mit jeder Ansteckung, das scheint eine Studie nahezulegen, steigt das Risiko für Long Covid

#M#, #D#, #Genetic, #Immundeficiency, #Infectious diseases, Deficiency of Mannose-binding lectin (MBL) as a cause of impaired pathogen defence, MBL genetic, Candida

Coronavirus disease 2019 (COVID-19) pandemic has taken the world by a storm, posing a gruelling challenge to the medical fraternity globally. Besides its very high infectivityinfectivity, significant organ dysfunction occurs in critically ill COVID-19 patients, leading to severe morbidity and mortal …

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2–specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell–associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine–-associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

The term ‘textbook’ should not be comforting. Textbooks tell us we can expect SARS-CoV-2 to have a detrimental impact on human health and life expectancy if it is allowed to continue to spread and reinfect the population.

npj Vaccines - Risk assessment of retinal vascular occlusion after COVID-19 vaccination

What the research shows about risks of myocarditis from COVID vaccines versus risks of heart damage from COVID – two pediatric cardiologists explain how to parse the data. Rare cases of myocarditis have been reported after COVID-19 vaccination, but the risk is higher after infection, and the prog

The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection.

Circadian rhythm may help determine when a vaccine offers the most protection

We previously described a nasally delivered monovalent adenoviral-vectored SARS-CoV-2 vaccine (ChAd-SARS-CoV-2-S, targeting Wuhan-1 spike [S]; iNCOVACC) that is currently used in India as a primary or booster immunization. Here, we updated the mucosal vaccine for Omicron variants by creating ChAd-SARS-CoV-2-BA.5-S, which encodes for a pre-fusion and surface-stabilized S protein of the BA.5 strain, and then tested monovalent and bivalent vaccines for efficacy against circulating variants including BQ.1.1 and XBB.1.5. Whereas monovalent ChAd-vectored vaccines effectively induced systemic and mucosal antibody responses against matched strains, the bivalent ChAd-vectored vaccine elicited greater breadth. However, serum neutralizing antibody responses induced by both monovalent and bivalent vaccines were poor against the antigenically distant XBB.1.5 Omicron strain and did not protect in passive transfer experiments. Nonetheless, nasally delivered bivalent ChAd-vectored vaccines induced robust antibody and spike-specific memory T cell responses in the respiratory mucosa, and conferred protection against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in the upper and lower respiratory tracts of both mice and hamsters. Our data suggest that a nasally delivered bivalent adenoviral-vectored vaccine induces protective mucosal and systemic immunity against historical and emerging SARS-CoV-2 strains without requiring high levels of serum neutralizing antibody. ### Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, Ocugen, Topspin, GlaxoSmithKline, Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions and Moderna. The Boon laboratory has received unrelated funding support in sponsored research agreements from GreenLight Biosciences Inc. The Boon laboratory has received funding support from AbbVie Inc., for the commercial development of SARS-CoV-2 mAb and Moderna for unrelated work. M.S.D., D.T.C., and I.P.D. are inventors of the ChAd-SARS-CoV-2-S vaccine technology, which Washington University has licensed to Bharat Biotech and Ocugen for commercial development.

New mask studies relying on a medical paradigm do not erase decades of engineering and occupational science that show they work

Nature Medicine - A new analysis using US Department of Veterans Affairs databases showed that reinfection is associated with increased risk of all-cause mortality, hospitalization and a wide range...

This report describes the risk for cardiac complications as higher after COVID-19 infection that after COVID-19 vaccination for males and females in all age groups.

This cohort study estimates rates of myocarditis and pericarditis after receipt of an mRNA COVID-19 vaccine among individuals in Ontario, Canada, stratified by recipients’ age and sex and by the vaccine product, schedule, and interdose interval.

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed co…

Study based on data from emergency services. COVID infection itself not linked to significant increase in cardiovascular complications.

Frédéric Sinistra war Belgier, dreifacher Kickboxer-Weltmeister, 40 Jahre alt - und massiver Corona-Leugner. Sein Widerstand ging so weit, dass er die Worte ´Corona´ und ´Covid´ nicht aussprechen wollte. Jetzt ist er tot - gestorben an Covid.

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2–3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics—cfPWV, AIx@HR75, and cDBP as well as DBP and MAP—responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2–3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

Aside from its traditional role in maintaining vascular hemodynamics and sodium balance, the renin–angiotensin–aldosterone system (RAAS) is established to have novel roles in inflammatory pathways, adipose biology, and cardiometabolic derangements....

Vaccination against COVID-19 increased immunity in the population, which reduced viral transmission and protected against severe disease. However, continuous emergence of SARS-CoV-2 variants required the implementation of bivalent boosters including the wild-type (D614G) and omicron (BA.5) spike. Improved effectiveness of the bivalent booster versus monovalent booster against omicron subvariants has been reported;1 however, few differences in the immune response have been detected.2 , 3 We investigated whether a bivalent COVID-19 booster vaccine that included wild-type spike and BA.5 spike induced detectable BA.5-specific antibody responses in serum. 16 serum samples collected at mean 31 days (SD 63 [range 0–260]) before and a mean 16 days (8 [6–31]) after receiving the bivalent booster were tested for antibody binding and avidity to the receptor binding domain (RBD) of wild-type and BA.5 SARS-CoV-2. Neutralisation of wild-type and BA.5 viruses was determined. Omicron-specific antibodies were measured by depletion of wild-type RBD reactive antibodies and assessment of depleted serum samples against BA.5 RBD. A substantial increase in antibody binding to wild-type and BA.5 RBD as well as in neutralisation of wild-type and BA.5 viruses was seen in serum samples after receiving the bivalent booster (figure, appendix p 6). There were substantial differences in binding of post-booster serum samples between wild-type and BA.5 RBDs; however, differences in neutralisation were not significant. Pre-booster and post-booster RBD antibody avidity was lower against BA.5 RBD than wild-type RBD, which prompted us to look for BA.5 specific antibodies. Wild-type RBD depleted serum samples had undetectable reactivity to wild-type RBD—as expected—and to BA.5 RBD, suggesting that a single exposure to BA.5 antigens by the administration of bivalent vaccine boosters does not elicit robust concentrations of BA.5 specific serum antibodies.

Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots[1][1]. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. and XBB.1 variants bind ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1 and XBB.1 RBDs bound to human ACE2 and S309 Fab (sotrovimab parent) explain the altered ACE2 recognition and preserved antibody binding through conformational selection. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1, the variant displaying the greatest loss of neutralization. Moreover, in several donors vaccine-elicited plasma antibodies cross-react with and trigger effector functions against Omicron variants despite reduced neutralizing activity. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring persistent immune imprinting. Our findings suggest that this previously overlooked class of cross-reactive antibodies, exemplified by S309, may contribute to protection against disease caused by emerging variants through elicitation of effector functions. ### Competing Interest Statement L.P., M.B., B.G., H.D., J.B., C.S.F., F.M., M.D., D.P., L.V., C.Sa., M.G., G.L., G.Le., C.M., E.D., A,R., R.A., D.J., S.S., K.C., E.C., G.Sc., J.Z., N.F., D.B. and J.N., F.A.L., N.C., M.A.S., L.A.P., G.S., A.L. and D.C. are employees of and may hold shares in Vir Biotechnology Inc. L.A.P. is a former employee and shareholder of Regeneron Pharmaceuticals and is member of the Scientific Advisory Board AI-driven Structure-enabled Antiviral Platform (ASAP). Regeneron provided no funding for this work. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Generate Biomedicines, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna and Emergent BioSolutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. [1]: #ref-1

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that can induce myopathy, which can evolve into potentially life-threatening muscle weakness, including diaphragmatic paralysis. We present a case report of a 57-year-old female treated in the medical ICU for acute respiratory distress syndrome (ARDS) triggered by active COVID-19 infection, who subsequently developed worsening respiratory weakness from underlying COVID-19 myopathy manifesting as respiratory muscle weakness. Our patient’s muscle biopsy highlights the development of muscle atrophy without evidence of inflammatory myopathy, making the presence of pre-existing autoimmune myopathy unlikely. While literature cites different biochemical etiologies for the development of myopathy, the exact mechanism behind this phenomenon is not yet defined.

Persistence of severe acute respiratory syndrome coronavirus 2 and reactivation of unrelated latent viruses may play a role in the development and pathogenesis of long COVID, and future research should focus on identifying the mechanisms behind these interactions.

Objective In a highly vaccinated Australian population we aimed to compare ongoing symptoms and functional impairment 12 weeks after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection. Methods and Analysis The study commenced upon a positive PCR test for either COVID-19 or influenza in June 2022 during concurrent waves of both viruses. Participants were followed up 12 weeks later in September 2022 and self-reported ongoing symptoms and functional impairment. We conducted a multivariate logistic regression analysis, controlling for age, sex, First Nations status, vaccination status, and socio-economic profile. Results There were 2 195 and 951 participants in the COVID-19 and influenza-positive cohorts respectively. After controlling for potential predictor variables, we found no evidence to suggest adults with COVID-19 were more likely to have ongoing symptoms (21.4% vs 23.0%, aOR 1.18; 95% CI 0.92-1.50) or moderate to severe functional impairment (4.1% vs 4.4%, OR 0.81; 95% CI 0.55-1.20) at 12 weeks after their diagnosis than adults who had influenza. Conclusions In a highly vaccinated population exposed to the SARS-CoV-2 omicron variant, long COVID may manifest as a post-viral syndrome of no greater severity than seasonal influenza but differing in terms of the volume of people affected and the potential impact on health systems. This study underscores the importance of long COVID research featuring an appropriate comparator group. What is already known on this subject? Post-acute infection syndromes are associated with a range of illnesses, including COVID-19 and influenza. “Long COVID” may pose a risk to health systems. What are the new findings? In a highly vaccinated population whose primary exposure has been to the Omicron variant, the rates of ongoing symptoms and moderate to severe functional impairment at 12 weeks after COVID-19 are no different to influenza. How might these results change the focus of research or clinical practice? The public health impact arising from long COVID may not stem from severity, but from volume. We do not dismiss the validity of long COVID but recommend an appropriate comparator group when researching this condition. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. It was undertaken by the Queensland Government Department of Health under section 83 of the Queensland Public Health Act 2005. All authors were officers of the Department of Health and were wholly responsible for all aspects of the design, implementation, and evaluation of this study. ### 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 was approved by the Metro South Health Research Ethics Committee (HREC/2022/QMS/88587) and the Queensland Office of Precision Medicine and Research (SSA/2022/QHC/88587). Participants were given information on the study prior to commencing the questionnaire and provided electronic consent by electing to participate. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000041651). 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 Requests for deidentified data associated with this research should be sent to the corresponding author after publication of the paper in the form of a formal data request which outlines the proposed use of this data and ensures appropriate attribution to this research.

The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5's immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven't been exposed to Omicron yet should receive two updated vaccine boosters. ### Competing Interest Statement X.S.X. and Y.C. are inventors on the provisional patent applications of BD series antibodies, which include BD55-5514 (SA55) and mAbs from Omicron infection convalescents. X.S.X. and Y.C. are founders of Singlomics Biopharmaceuticals. Other authors declare no competing interests.