Covid19-Sources

As the government drops its restrictions, it not only needs to convince people that the virus is nothing to fear, but also that inoculations are essential.

Im Jahr 2021 sind in Deutschland nach endgültigen Ergebnissen der Todesursachenstatistik insgesamt 1 023 687 Menschen verstorben, davon waren 515 559 Männer und 508 128 Frauen. Wie das Statistische Bundesamt (Destatis) weiter mitteilt, stieg die Zahl der Todesfälle damit um 3,9 % gegenüber dem Vorjahr (2020: 985 572 Verstorbene). An COVID-19 als Grundleiden verstarben im Jahr 2021 in Deutschland insgesamt 71 331 Menschen, das waren 79 % mehr als im Vorjahr (2020: 39 758). Damit war COVID-19 bei 7,0 % aller Verstorbenen die ausschlaggebende Todesursache.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypo…

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

Nature - Msemburi et al. describe how the World Health Organization has estimated the excess mortality associated with the COVID-19 pandemic, by month and for 2020 and 2021, and analyse their...

Early on during a pandemic, vaccine availability is limited, requiring prioritisation of different population groups. Evaluating vaccine allocation is therefore a crucial element of pandemics...

The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Background The current respiratory viral season in Ontario started early with an intensity experienced throughout the pediatric health system. We sought to examine trends in patient volumes and level of care intensity among children admitted with laboratory-confirmed respiratory viral infection over the last five years in Ottawa. Methods This was a retrospective cohort study of patients at CHEO, a pediatric health centre in Ottawa, who were diagnosed with a laboratory-confirmed respiratory viral infection in the first 72 hours of admission between October 22, 2017 and December 10, 2022. Their admissions were stratified by age groups and levels of care intensity and evaluated for trends over six surveillance periods that begin in Week 35 and end in Week 34 of the following calendar year. Results During this current surveillance period, there was an early, rapid, two-fold increase in admissions due to respiratory viral infections compared to previous periods, driven largely by RSV and influenza. While there were similar age distributions, there was a larger volume of Level 2 and 3 admissions, and higher proportion of patients requiring Level 2 intensity of care (20.8% versus 2.2% to 12.0% in pre-pandemic years; p

Scientists predict China will see the largest COVID surge of the pandemic this winter, with hundreds of millions of people infected. But some experts say that it could have been even worse.

COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions, however the exact mechanism of damage is still unknown. In this study, we downloaded testicular bulk-RNA-seq data from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis. These result give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage.

BioNanoScience - In recovered COVID-19 patients, the state of mucosal immunity remains understudied. Cytological, functional, and metabolic characteristics of neutrophils and the interleukin status...

The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

Diese #COVID19-Studie analysiert auf Ebene einzelner Zellen die Auswirkungen einer Infektion mit dem #SARSCoV2-Virus. Nach einer Infektion fehlte eine Untergruppe der naiven T-Zellen bei den genesenen Personen. Der Verlust dieser Population naiver CD4+ T-Zellen deutet auf… pic.twitter.com/rwyswANFFs— Ralf Wittenbrink (@RWittenbrink) December 3, 2022

The WHO COVID-19 Clinical management: living guidance contains the Organization’s most up-to-date recommendations for the clinical management of people with COVID-19.

Nature Aging - Mavrikaki et al. show that severe COVID-19 is associated with molecular signatures of aging and low cognitive performance in the human frontal cortex; and emphasize the value of...

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

It really is a remarkable achievement and maybe a lot of luck that the world mundanely operates with such a complex indicator as life expectancy. Unlike many statistics and quantities of general use that are being monitored and reported regularly...

Nature - NeoCoV and its close relative, PDF-2180, can efficiently bind to and use specific bat ACE2 orthologues and, less favourably, human ACE2 as entry receptors through their receptor-binding...

Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving.

Family members and health care workers should take precautions, experts said.

This cross-sectional study estimates BNT162b2 vaccine effectiveness against SARS-CoV-2 infection among children aged 5 to 11 years during Delta and Omicron variant–predominant periods, by prior SARS-CoV-2 infection status and Omicron sublineage.

Pericardial effusion (PE) related to COVID-19 has rarely been observed, with most reported cases being non-hemorrhagic. This study aims to present a r…

A new study studies the vaccine effectiveness and death in the Veterans Health Administration.

COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing sympto…

Updates This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question What is the role of drugs in the treatment of patients with covid-19? Context The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19. New or updated recommendations • Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use. Understanding the new recommendations When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted. Prior recommendations • Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial. About this guideline This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ . These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations Recommendations on anticoagulation are planned for the next update to this guideline.

he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reminded us of the critical role of an effective host immune response and the devastating effect of immune dysregulation. This year marks 10 years since the first description of a cytokine storm that developed after chimeric antigen receptor (CAR) T-cell therapy1 and 27 years since the term was first used in the literature to describe the engraftment syndrome of acute graft- versus-host disease after allogeneic hematopoietic stem-cell transplantation.2 The term “cytokine release syndrome” was coined to describe a similar syndrome after infusion of muromonab-CD3 (OKT3).3 Cytokine storm and cytokine release syn- drome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be trig- gered by various therapies, pathogens, cancers, autoimmune conditions, and monogenic disorders. From a historical perspective, cytokine storm was previously referred to as an influenza-like syndrome that occurred after systemic infections such as sepsis and after immunotherapies such as Coley’s toxins.4 Yersinia pestis infection (i.e., the plague) has led to major pandemics (e.g., the Black Death) and triggers alveolar macrophages to produce excessive amounts of cytokines, resulting in cytokine storm.5 An exaggerated immune response was suspected to contribute to the lethal- ity of the 1918–1919 influenza pandemic. In fact, a reconstructed H1N1 virus isolated from the 1918 pandemic, as compared with common reference strains of the virus that causes influenza A, triggered marked pulmonary inflammation in mice.6 Recognition that the immune response to the pathogen, but not the patho- gen itself, can contribute to multiorgan dysfunction and that similar cytokine storm syndromes could occur with no obvious infection led to the investigation of immunomodulators and cytokine-directed therapies. One of the earliest targeted therapies for abrogation of a cytokine storm was the anti–interleukin-6 receptor monoclonal antibody tocilizumab, which was developed for the treatment of idio- pathic multicentric Castleman’s disease in the 1990s. A host of other disorders have been described as causes of cytokine storm and targeted with immune-di- rected therapies, such as sepsis, primary and secondary hemophagocytic lympho- histiocytosis (HLH), autoinflammatory disorders, and coronavirus disease 2019 (Covid-19).

Improved understanding of the effects of meteorological conditions on the transmission of SARS-CoV-2, the causative agent for COVID-19 disease, is urgently needed to inform mitigation efforts. Here, we estimated the relationship between air temperature or specific humidity (SH) and SARS-CoV-2 transmission in 913 U.S. counties with abundant reported infections from March 15 to August 31, 2020. Specifically, we quantified the associations of daily mean temperature and SH with daily estimates of the SARS-CoV-2 reproduction number ( Rt ) and calculated the fraction of Rt attributable to these meteorological conditions. Both lower temperature and lower SH were significantly associated with increased Rt . The fraction of Rt attributable to temperature was 5.10% (95% eCI: 5.00 - 5.18%), and the fraction of Rt attributable to SH was 14.47% (95% eCI: 14.37 - 14.54%). These fractions generally were higher in northern counties than in southern counties. Our findings indicate that cold and dry weather are moderately associated with increased SARS-CoV-2 transmissibility, with humidity playing a larger role than temperature. ### Competing Interest Statement J.S. and Columbia University disclose partial ownership of SK Analytics. J.S. discloses consulting for BNI. All other authors declare no competing interests. ### Funding Statement Y.M. received funding from the China Scholarship Council (201906320022). S.P. and J.S. acknowledged funding from the National Institutes of Health (GM110748) and the National Science Foundation (DMS-2027369), as well as a gift from the Morris-Singer Foundation. R.D. received funding from the High Tide Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Not Human Subject Research. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Estimates of county-level reproduction number are available at https://github.com/shaman-lab/Counterfactual The data sets used in the study are publicly available from the following locations: Hourly air temperature and specific humidity data: https://disc.gsfc.nasa.gov/datasets/NLDAS\_FORA0125\_H\_002/summary?keywords=NLDAS Population density, median household income, percent of people older than 60 years, percent black residents, percent Hispanic residents, percent owner-occupied housing, and percent residents aged 25 years and over without a high school diploma: https://www.census.gov/data/tables.html U.S. county boundary: https://www.census.gov/geographies/mapping-files/time-series/geo/cartographic-boundary.html Prevalence of smoking and obesity among adults in each county: https://www.countyhealthrankings.org/explore-health-rankings/rankings-data-documentation Total ICU beds in each county: https://khn.org/news/as-coronavirus-spreads-widely-millions-of-older-americans-live-in-counties-with-no-icu-beds/ Annual PM2.5 concentrations in the U.S. from 2014 to 2018: http://fizz.phys.dal.ca/~atmos/martin/?page\_id=140 Short-term daily mean PM2.5 and daily maximum 8-hour O3: https://www.epa.gov/outdoor-air-quality-data/download-daily-data Daily downward UV radiation at the surface: https://cds.climate.copernicus.eu/cdsapp#!/dataset/reanalysis-era5-single-levels?tab=overview

Globally, the spread and severity of COVID-19 have been distinctly non-uniform. Seasonality was suggested as a contributor to regional variability, but the relationship between weather and COVID-19 remains unclear and the focus of attention has been on ...

Scientific Data - High-resolution estimates of social distancing feasibility, mapped for urban areas in sub-Saharan Africa