Covid19-Sources

Prominently accountable for the upsurge of COVID-19 cases as the world attempts to recover from the previous two waves, Omicron has further threatened the conventional therapeutic approaches....

A Phase III Confirmatory Study of K-237 - Full Text View.

Viruses interact extensively with the host molecular machinery, but the underlying mechanisms are poorly understood. Bacteriophage T7 recruits the small protein thioredoxin of the Escherichia coli host as an essential processivity factor for the viral DNA polymerase. We challenged the phage t …

Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for epidemic modeling, and for individual risk evaluation. In this study, we present the first estimates of these rates using multi-country serology studies, and data on hospital admissions and mortality from early to mid-2020. We integrated data from those sources using a Bayesian model that accounts for the high heterogeneity between data sources and for the uncertainty associated to the estimates reported from each data source. Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. Importantly, the estimated rate of severe disease outcome in adolescents is between one and two orders of magnitude larger than the reported rate of vaccine side-effects, showing how these estimates are relevant for health policy. Finally, we validate our results by showing that they are in close agreement with the estimates obtained from an indirect method that uses reported infection fatality rates estimates and hospital mortality data.

Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (43-62%) for hospitalization; 89% (67-116%) for ICU admission; and 51% (30-74%) for death. Increases with Delta variant were more pronounced: 108% (80-138%) for hospitalization; 234% (164-331%) for ICU admission; and 132% (47-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-240 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred41 in the absence of VOC emergence.

COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multipl…

An in-depth analysis of IFNs in COVID-19 reveals differences in their roles based on anatomical location, viral load, age, and disease severity. In the upper respiratory tract, high levels of IFN-III are protective and result in mild disease in spite of higher SARS-CoV-2 viral burden, while the lower airways of patients with severe COVID-19 demonstrate elevated IFN-I and IFN-III, cell death, and a reduction in IFN-stimulated genes.

BACKGROUND Waning of COVID-19 vaccine protection and emergence of SARS-CoV-2 Omicron (B.1.1.529) variant have expedited efforts to scale up booster vaccination. This study compared protection afforded by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines, compared to the primary series of only two doses in Qatar, during a large, rapidly growing Omicron wave. METHODS In a population of 2,232,224 vaccinated persons with at least two doses, two matched, retrospective cohort studies were implemented to investigate effectiveness of booster vaccination against symptomatic SARS-CoV-2 infection and against COVID-19 hospitalization and death, up to January 9, 2022. Association of booster status with infection was estimated using Cox proportional-hazards regression models. RESULTS For BNT162b2, cumulative symptomatic infection incidence was 2.9% (95% CI: 2.8-3.1%) in the booster-dose cohort and 5.5% (95% CI: 5.3-5.7%) in the primary-series cohort, after 49 days of follow-up. Adjusted hazard ratio for symptomatic infection was 0.50 (95% CI: 0.47-0.53). Booster effectiveness relative to primary series was 50.1% (95% CI: 47.3-52.8%). For mRNA-1273, cumulative symptomatic infection incidence was 1.9% (95% CI: 1.7-2.2%) in the booster-dose cohort and 3.5% (95% CI: 3.2-3.9%) in the primary-series cohort, after 35 days of follow-up. The adjusted hazard ratio for symptomatic infection was 0.49 (95% CI: 0.43-0.57). Booster effectiveness relative to primary series was 50.8% (95% CI: 43.4-57.3%). There were fewer cases of severe COVID-19 in booster-dose cohorts than in primary-series cohorts, but cases of severe COVID-19 were rare in all cohorts. CONCLUSIONS mRNA booster vaccination is associated with modest effectiveness against symptomatic infection with Omicron. The development of a new generation of vaccines targeting a broad range of variants may be warranted. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health, Hamad Medical Corporation, and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors. ### 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: Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards approved this retrospective study with waiver of informed consent. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (). Aggregate data are available within the manuscript and its Supplementary information.

Das Paul-Ehrlich-Institut hat in Zusammenarbeit mit der Universität Frankfurt am Main die Langzeit-Antikörperreaktion nach SARS-CoV-2-Infektion bei 828 Personen mit verschiedenen COVID-19-Schweregraden untersucht. Gemessen wurden bindende Antikörper gegen unterschiedliche SARS-CoV-2-Zielantigene, neutralisierende Antikörper und die Stärke der Antikörperbindung (Antikörperavidität). Sensitivität, Kinetik und Dauer des Antikörpernachweises waren abhängig von detektierter Antikörperklasse, Testdesign, Zielantigen des Anti-SARS-CoV-2-Antikörpertests sowie von Antikörperavidität und COVID-19-Schweregrad.

Background Prior studies have documented reliable associations between SARS-CoV-2 infection and adverse cognitive impact in older adults. The current study sought to determine whether SARS-CoV-2 infection and COVID-19 symptom severity are associated with cognitive dysfunction among young adults and middled-aged adults in the general population. Method The Canadian COVID-19 Experiences Project (CCEP) survey involves 1,958 adults with equal representation of vaccinated and vaccine hesitant adults between the ages of 18 and 54 years. The sample comprised 1,958 adults with a mean age of 37 years ( SD =10.4); 60.8% were female. The primary outcome was symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated decision-making task. Results Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of symptoms of executive dysfunction ( M adj =1.89, SE =0.08, CI : 1.74, 2.04; n =175) than their non-infected counterparts ( M adj =1.63, SE =0.08, CI : 1.47,1.80; n =1,599; β=0.26, p =.001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of executive dysfunction, with moderate (β=0.23, CI : 0.003-0.46) and very/extremely severe (β= 0.69, CI : 0.22-1.16) COVID-19 symptoms being associated with significantly greater dysfunction, compared to asymptomatic. These effects remained reliable and of similar magnitude after controlling for age, sex, vaccination status, income, and geographic region, and after removal of those who had been intubated during hospitalization. Similar effects were found for the decision-making task. Conclusions Positive SARS-CoV-2 infection history and COVID-19 symptom severity are associated with executive dysfunction among young and middle-aged adults with no history of medically induced coma. These findings are evident on self-reported and task-related indicators of cognitive function. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by an operating grant to P. Hall (PI), G. Fong (co-PI) and S. Hitchman (co-I) by the Canadian Institutes for Health Research (CIHR), Institute for Population and Public Health (GA3-177733). ### 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: This study protocol was reviewed by and received approval from the University of Waterloo Office of Research Ethics. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Due to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS-CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern. ### Competing Interest Statement S.C. was a member of a clinical advisory board for Biontech. T.W. received speaker and consultancy fees from Gilead Sciences, Merck Sharp Dome, and Janssen Pharmaceuticals. All other authors declare no conflict of interest. ### Funding Statement This study has been performed with the support of the Goethe-Corona-Fund of the Goethe University Frankfurt (MW) and the Federal Ministry of Education and Research (COVIDready; grant 02WRS1621C (MW). We are thankful for the numerous donations to the Goethe-Corona-Fund and the support of our SARS-CoV-2 research. ### 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 conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the Ethics Committee of the Faculty of Medicine at Goethe University Frankfurt (2021-201, 20-864 and 250719). 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Sequences are available on GISAID (www.gisaid.org, access date 12/2021), under the following accession numbers. Omicron strains used in this study are as follows: B.1.1.529 (EPI\_ISL\_6959868; GenBank ID: [OL800703][1]), B.1.1.529 (EPI\_ISL\_6959871; GenBank ID: [OL800702][2]) . GenBank accession number for the SARS-CoV-2 B.1.617.2 (Delta) isolate IND8424/2021 ( GenBank ID: [MZ315141][3]). [1]: /lookup/external-ref?link_type=GEN&access_num=OL800703&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom [2]: /lookup/external-ref?link_type=GEN&access_num=OL800702&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom [3]: /lookup/external-ref?link_type=GEN&access_num=MZ315141&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom

To estimate the growth of the Omicron variant of concern (1) and its immune escape (2–9) characteristics, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel. We undertook separate analyses according to two case definitions. For the first definition, we included all cases with a definitive negative S-gene Target Failure (SGTF) result and specimen dates between 29/11/2021 and 11/12/2021 inclusive. For the second definition, we included cases with a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive. We chose a later start date for the SGTF definition to ensure greater specificity of SGTF for Omicron. We used logistic and Poisson regression to identify factors associated with testing positive for Omicron compared to non-Omicron (mostly Delta) cases. We explored the following predictors: day, region, symptomatic status, sex, ethnicity, age band and vaccination status. Our results suggest rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (95% CI: 0.33-0.35) [2.0 day doubling time] over the study period from both SGTF and genotype data. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta. Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta. To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection we used conditional Poisson regression to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting our analysis to symptomatic cases and matching by day, region, 10-year age band, sex and ethnicity. We found a significant increased risk of an Omicron case compared to Delta for those with vaccine status AZ 2+weeks post-dose 2 (PD2) , Pfizer 2+w PD2, AZ 2+w post-dose 3 (PD3) and PF 2+w PD3 vaccine states with hazard ratios of 1.86 (95%CI: 1.67-2.08), 2.68 (95%CI: 2.54-2.83), 4.32 (95%CI: 3.84-4.85) and 4.07 (95%CI: 3.66-4.51), respectively, where PD3 states are categorised by the dose 1/2 vaccine used. Depending on the Delta VE estimates used (10), these estimates translate into Omicron VE estimates of between 0% and 20% PD2 and between 55% and 80% PD3 against Omicron, consistent with other estimates (11). Similar estimates were obtained using genotype data, albeit with greater uncertainty. To assess the impact of Omicron on reinfection rates we relied on genotype data, since SGTF is associated with a higher observed rate of reinfection, likely due to reinfections typically having higher Ct values than primary infections and therefore being subject to a higher rate of random PCR target failure. Controlling for vaccine status, age, sex, ethnicity, asymptomatic status, region and specimen date and using conditional Poisson regression to predict reinfection status, Omicron was associated with a 5.41 (95% CI: 4.87-6.00) fold higher risk of reinfection compared with Delta. This suggests relatively low remaining levels of immunity from prior infection.

Alte und neue Seuchen bedrohen auch Deutschland - und das liegt nicht nur am Klimawandel

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity to Delta32 and Omicron SARS-CoV-2 variants in 239 samples from 125 fully vaccinated individuals. In uninfected, non-boosted individuals, VLP neutralization titers to Delta and Omicron were reduced 2.7-fold and 15.4-fold, respectively, compared to wild-type (WT), while boosted individuals (n=23) had 18-fold increased titers. Delta breakthrough infections (n=39) had 57-fold and 3.1-fold titers whereas Omicron breakthrough infections (n=14) had 5.8-fold and 0.32-fold titers compared to uninfected non-boosted and boosted individuals, respectively. The difference in titers (p=0.049) was related to a higher proportion of moderate to severe infections in the Delta cohort (p=0.014). Correlation of neutralizing and spike quantitative antibody titers was decreased with Delta or Omicron compared to WT. Neutralizing antibodies in Delta and Omicron breakthrough infections increase overall, but the relative magnitude of increase is greater in more clinically severe infection and against the specific infecting variant.

There is considerable variation in disease severity among patients infected with SARS-CoV-2, the virus that causes COVID-19. Human genetic variation can affect disease outcome, and the coronaviruses SARS-CoV, SARS-CoV-2, and HCoV-NL63 utilize human ACE2 ...

A 58-year-old woman who died of COVID infection was included as a control subject in an ongoing autopsy study of the neuropathology of military traumatic brain

This study examines the antibody responses to a third dose (100 μg) of the mRNA-1273 SARS-CoV-2 vaccine among kidney transplant recipients in France who had not responded to 2 doses of the vaccine.

Correspondence from The New England Journal of Medicine — Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients

An Covid-19 sterben Menschen. Aber warum eigentlich genau? Wieso hat der Großteil der Betroffenen kaum oder nur leichte Symptome, während andere so sc

OK ich wage mich nochmal an ein schwieriges Thema. Bitte erst zu Ende lesen und dann kommentieren.Wenn es darum geht, dass wir irgendwann Infektionen zulassen müssen damit die Normalität wieder einkehren kann wird oft darauf hingewiesen, dass es Patienten mit Immunsuppression— ECMO_Doc (@doc_ecmo) January 29, 2022

Wer eine Infektion mit SARS-CoV-2 überstanden hat, kann erneute Attacken des Virus erstaunlich effektiv abwenden. Dies gilt auch für den Fall, dass der Verlauf nur milde oder sogar asymptomatisch war. Das Potenzial der Genesenen könnte sich zudem als...

📌Not a good signal—somehow in the original 🇿🇦 epicenter of #Omicron, #BA2 subvariant has suddenly become dominant ~58% now, displacing old BA1 strain. Same thing happened in Denmark 🇩🇰 where BA2 is now over 65% dominant. HT @JosetteSchoenma #COVID19 pic.twitter.com/Mf0bChrc89— Eric Feigl-Ding (@DrEricDing) January 28, 2022

Nature Medicine - High levels of neutralizing antibodies are successfully elicited against SARS-CoV-2 variants of concern, including omicron, after three exposures to the viral spike protein,...

European Journal of Pediatrics - Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2...

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses.The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic ...

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors[1][1]–[4][2]. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic[5][3]. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes’ S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using “MERS-CoV-2” with both high fatality and transmission rate. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-4 [3]: #ref-5

This report describes COVID-19 cases and hospitalizations by vaccination status and previous COVID-19 diagnosis before and after the Delta variant became predominant.

This filtered @Nextstrain build gives a nice visual display of how distant the Omicron family is from everything else, & how different BA.1 (21K) & BA.2 (21L) are from each other. Distance is in mutations.https://t.co/mrPRngyQFv pic.twitter.com/IXOOFZ9yy4— Dr Emma Hodcroft (@firefoxx66) January 27, 2022