Covid19-Sources

Myocarditis mortality rate ratios (MMRRs) and their 95% confidence intervals (95% CIs) after10 receiving SARS-CoV-2 vaccine compared with that in the reference population (previous 3 years)11 were significantly higher not only in young adults (highest in the 30s with MMRR of 6.69) but also12 in the elderly. Standardised mortality ratio (SMR) for myocarditis was 1.65 (1.07 to 2.55) for those13 60 years or older and 2.01 (1.44 to 2.80) in overall age. The risk of myocarditis mortality in the14 SARS-CoV-2 vaccinated population may be 4 times or higher than the apparent MMRRs15 considering healthy vaccinee effect. Unreported post-vaccination deaths should also be considered16 as suggested by the extremely high myocarditis mortality odds ratio (205.60; 133.52 to 311.94)

1/ 🧵Zweite Studie zu BA.5-Impfstoffen. Zunächst zu Ergebnissen, dann allg. Einordnung. Es wurden Ak-Titer bei 15/18 Pers. nach WT- und BA.5/WT-Booster verglichen. Nach BA.5/WT Titer gg. BA.5 1.3x höher 3 Wochen post-Vacc.als nach WT. Das entspricht➡️https://t.co/LHnogyJRxY pic.twitter.com/4hu6Ep52Xs— Jan Hartmann (@pelagicbird) October 26, 2022

⚠️BREAKING—CDC now confirms my scoop that super evasive #BQ1 & #BQ11 variants (Typhon & Cerberus) have meteorically surged from *unlisted* 3 weeks ago, to 11% 2 weeks ago—to ⬆️now suddenly 27% today! This is a bad 10-day doubling time! 🇬🇧’s #BQ ~30% too🧵https://t.co/amAjDWufhr pic.twitter.com/TGBFPAgpFJ— Eric Feigl-Ding (@DrEricDing) October 28, 2022

The SARS-CoV-2 pandemic has highlighted the need for vaccines that not only prevent disease, but also prevent transmission. Parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here we describe the development of a vaccine strategy we term “prime and spike” that leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, IgA at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables induction of cross-reactive immunity against sarbecoviruses.

Just 10 months after the initial genome sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, two mRNA vaccines were demonstrated to provide 95% efficacy against symptomatic infections via randomized, placebo-controlled trials of more than 74,000 participants (1). That unprecedented success was, in part, fueled by the $10 billion governmental investment in Operation Warp Speed (OWS) in March 2020 to accelerate the development, manufacturing, and distribution of coronavirus disease 2019 (COVID-19) vaccines. We urgently need such an accelerated initiative now for nasal vaccines. During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time, we have seen a succession of important variants of concern with increasing transmissibility and immune evasion, culminating in the Omicron lineages. With that, there has been a marked falloff in the capacity for vaccinations and booster shots to block infections and transmission (2). A major unmet clinical need has arisen to block the transmission chain, prevent the frequent breakthrough infections, and achieve high levels of durable protection against severe disease, no less prevent post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID).

Nature Medicine - Findings from the COVID-19 in Pregnancy in Scotland (COPS) study reveals low levels of vaccination uptake by pregnant women compared to women in the general population and that...

Nature Medicine - Findings from the COVID-19 in Pregnancy in Scotland (COPS) study reveals low levels of vaccination uptake by pregnant women compared to women in the general population and that...

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection.

The risk of stillbirth was quadruple with the Delta variant compared with uninfected women, and maternal death rates quintupled after Delta.

„Die Pandemie ist noch nicht vorbei“Globale Mortalitätstrends deuten auf eine anhaltend hohe Übersterblichkeit in den letzten 12 Monaten hin und legen nahe, dass die Pandemie noch nicht vorbei ist. In den vergangenen 12 Monaten lag die globale Übersterblichkeit 🧵#COVID19 pic.twitter.com/DuUoeg2jJH— Ralf Wittenbrink (@RWittenbrink) October 28, 2022

Schützt der angepasste #Booster (BA.4/5) besser vor den neuen Varianten als der ursprüngliche? Zwei Arbeiten lassen vermuten, dass dem nicht so ist. Gestern und vorgestern als Pre-Print erschienen. Aber ganz so einfach ist es nicht. Schau ma uns die Burschen mal an. 1/11— Martin Moder (@Martin_Moder) October 26, 2022

Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.5 is currently the dominant SARS-CoV-2 variant and substantially evades neutralizing antibodies (NAbs). Our data show that BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters. ### Competing Interest Statement The authors have declared no competing interest.

Along with the pneumonia, blood clots, and other serious health concerns caused by SARS-CoV-2, the COVID-19 virus, some studies have also identified another troubling connection. Some people can

These landscape documents have been prepared by the World Health Organization (WHO) for information purposes only concerning the 2019-2020 global of the novel coronavirus.

Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants, as well as their ancestral BA.4/5, BA.2.75 and D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation, and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing, resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants. ### Competing Interest Statement The authors have declared no competing interest.

Understanding the evolution of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we tracked SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses declined by two- to four-fold through the study period. Breakthrough infection elicited minimal de novo Omicron-specific B cell responses but drove affinity maturation of pre-existing cross-reactive MBCs toward BA.1. Public clones dominated the neutralizing antibody response at both early and late time points, and their escape mutation profiles predicted newly emergent Omicron sublineages. The results demonstrate that heterologous SARS-CoV-2 variant exposure drives the evolution of B cell memory and suggest that convergent neutralizing antibody responses continue to shape viral evolution. ### Competing Interest Statement C.I.K. is a former employee and holds shares in Adimab. LLC. P.K., H.L.D., E.R.C., and J.C.G. are current employees and hold shares in Adimab LLC. L.M.W. is an employee and holds shares in Invivyd Inc. T.N.S. and J.D.B. consult with Apriori Bio. J.D.B. has consulted for Moderna and Merck on viral evolution and epidemiology. D.R.B. is a consultant for IAVI, Invivyd, Adimab, Mabloc, VosBio, Nonigenex, and Radiant. C.I.K. and L.M.W. are inventors on a provisional patent application describing the SARS CoV 2 antibodies reported in this work. T.N.S. and J.D.B. may receive a share of intellectual property revenue as inventors on Fred Hutchinson Cancer Center optioned technology and patents related to deep mutational scanning of viral proteins. The other authors declare that they have no competing interests.

We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokin …

HIV researchers who have made the crossover to studying long COVID-19 are finding unmistakable similarities, but coronaviruses are not retroviruses like HIV, nor are they sexually transmitted like HIV.

Australian researchers have for the first time discovered COVID-19 causes DNA damage to the heart, giving clues to why the diseases causes heart complications in some people.

COVID-19 causes cardiac dysfunction in up to 50% of patients, but the pathogenesis remains unclear. Infection of human iPSC-derived cardiomyocytes with SARS-CoV-2 revealed robust transcriptomic and morphological signatures of damage in cardiomyocytes. These morphological signatures include a distinct pattern of sarcomere fragmentation, with specific cleavage of thick filaments, and numerous iPSC-cardiomyocytes that lacked nuclear DNA. Human autopsy specimens from COVID-19 patients also displayed marked sarcomeric disruption and similar fragmentation, as well as prevalently enucleated cardiomyocytes. These striking transcriptomic and cytopathic changes provide a roadmap to understand the mechanisms of COVID-19 cardiac damage, search for potential treatments, and determine the basis for prolonged cardiac morbidity observed in this pandemic.

The SARS-CoV-2 Omicron variant and its numerous sub-lineages have exhibited a striking ability to evade humoral immune responses induced by prior vaccination or infection. The Food and Drug Administration (FDA) has recently granted Emergency Use Authorizations (EUAs) to new bivalent formulations of the original Moderna and Pfizer mRNA SARS-CoV-2 vaccines that target both the ancestral strain as well as the Omicron BA.4/BA.5 variant. Despite their widespread use as a vaccine boost, little is known about the antibody responses induced in humans. Here, we collected sera from several clinical cohorts: individuals after three or four doses of the original monovalent mRNA vaccines, individuals receiving the new bivalent vaccines as a fourth dose, and individuals with BA.4/BA.5 breakthrough infection following mRNA vaccination. Using pseudovirus neutralization assays, these sera were tested for neutralization against an ancestral SARS-CoV-2 strain, several Omicron sub-lineages, and several related sarbecoviruses. At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5. Those who received a fourth monovalent vaccine dose had a slightly higher neutralizing antibody titers than those who received the bivalent vaccine against three related sarbecoviruses: SARS-CoV, GD-Pangolin, and WIV1. When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation. ### Competing Interest Statement D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to WuXi Biologics and Brii Biosciences, and board director for Vicarious Surgical. Aubree Gordon serves on a scientific advisory board for Janssen Pharmaceuticals. Other authors declare no competing interests.

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.

The current report presents the case of a 76-year-old man with Parkinson’s disease (PD) who died three weeks after receiving his third COVID-19 vaccination. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov-19 vector vaccine, followed by two doses of the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to ambiguous clinical signs before death. PD was confirmed by post-mortem examinations. Furthermore, signs of aspiration pneumonia and systemic arteriosclerosis were evident. However, histopathological analyses of the brain uncovered previously unsuspected findings, including acute vasculitis (predominantly lymphocytic) as well as multifocal necrotizing encephalitis of unknown etiology with pronounced inflammation including glial and lymphocytic reaction. In the heart, signs of chronic cardiomyopathy as well as mild acute lympho-histiocytic myocarditis and vasculitis were present. Although there was no history of COVID-19 for this patient, immunohistochemistry for SARS-CoV-2 antigens (spike and nucleocapsid proteins) was performed. Surprisingly, only spike protein but no nucleocapsid protein could be detected within the foci of inflammation in both the brain and the heart, particularly in the endothelial cells of small blood vessels. Since no nucleocapsid protein could be detected, the presence of spike protein must be ascribed to vaccination rather than to viral infection. The findings corroborate previous reports of encephalitis and myocarditis caused by gene-based COVID-19 vaccines.

#Nature: Durch #SARSCoV2 entstehen schwerwiegende Folgen für #Patienten & #GesellschaftPatienten, die die ersten 30 Tage einer akuten #SARSCoV2-Erkrankung überleben, haben nach 1 Jahr ein erhöhtes Risiko für neurologische Erkrankungen #LongCovid https://t.co/N5n5eFSykk— Bert Weingarten (@WeingartenDE) October 4, 2022

IMPORTANCE During the COVID-19 pandemic children and adolescents were massively infected worldwide. In 2022 reinfections became increasingly common and they may continue to be a main feature of the endemic phase of SARS-CoV-2. It is important to understand the epidemiology and clinical impact of reinfections. OBJECTIVE To assess the incidence, risk, and severity of SARS-CoV-2 reinfection in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS A population-level observational study was performed using surveillance data from the Autonomous Province of Vojvodina, Serbia between March 6, 2020 and April 30, 2022 with follow-up until July 31, 2022. The population-based sample consisted of 32 524 residents of Vojvodina

Auch Kinder und Jugendliche können nach leichten Verläufen Long-COVID-Symptome entwickeln. Wir sprachen mit dem Jenaer Kinderarzt Daniel Vilser darüber.

COVID könnte mehrere Organe 3-4 Jahre schneller altern lassen Nach über zweieinhalb Jahren #COVID-Forschung sehen die Wissenschaftler die ersten Daten, die eine dramatische Veränderung der menschlichen Organe nach einer #COVID19-Infektion belegen.#LongCovid #Corona pic.twitter.com/j93mIjmFof— Ralf Wittenbrink (@RWittenbrink) October 18, 2022

Nature Human Behaviour - In 2021, life expectancies returned to pre-pandemic levels in parts of western Europe but further worsened in eastern Europe, the United States and Chile. Life expectancy...