Covid19-Sources

The new SARS-CoV-2 variant (EG.5.1), how we are about to FLip, and where are the new Covid boosters?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality[1][1],[2][2]. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from FAEPEX-UNICAMP (#2295/20, #2458/20, #2266/20 and #2274/20), Sao Paulo Research Foundation (FAPESP) (#2019/16116-4, #2019/06372-3, #2020/04583-4, #2013/08293-7, #2020/04579-7, #2015/15626-8, #2018/14933-2, #2020/04746-0, #2019/00098-7, #2020/04919-2, #2017/01184-9), the National Institute of Science and Technology in Neuroimmunomodulation (INCT-NIM) (#465489/2014-1) and FINEP (#01.20.0003.00). A.S.F. and M.A.M. were supported by CNPq productivity awards (#306248/2017-4 and #310287/2018-9). A.J.R.F, G.G.D., A.C.C., N.S.B., L.B.M., F.C., V.C.C., A.B., T.L.K, G.S.P., R.G.L. were supported by FAPESP fellowships (#2019/17007-4, #2019/22398-2, #2019/05155-9, #2019/06459-1, #2019/04726-2, #2017/23920-9, #2016/24163-4, #2016/23328-0). V.O.B. and L.N.S. were supported by FAEPEX fellowship (#2295/20 and #2319/20). D.M. was supported by CAPES fellowship. ### 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 present study was approved by the University of Campinas Committee for Ethical Research (CAAE number 32078620.4.0000.5404). 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 are storage in the university databank and will be provided under reasonable request. [1]: #ref-1 [2]: #ref-2

s and their male partners in the United States and Canada. Female participants completed a baseline questionnaire and then follow-up questionnaires every 8 weeks until pregnancy, during early and late pregnancy, and during the postpartum period. Vaccine information was self-reported on all questionnaires. Miscarriage was identified from self-reported information during follow-up. Male partners were invited to complete a baseline questionnaire only. We used Cox proportional hazard models to estimate the hazard ratio (HR) and 95% CI for the association between vaccination less than 3 months before pregnancy detection through the 19th week of pregnancy and miscarriage, with gestational weeks as the time scale. We modeled vaccination as a time-varying exposure and used propensity-score fine stratification to control for confounding from seasonal and female partner factors. RESULTS: Of 6,946 pregnancies, 23.3% of female partners reported exposure to influenza vaccine before or during pregnancy: 3.2% during pregnancy (gestational age 4–19 weeks) and 20.1% during the 3 months before pregnancy detection. The miscarriage rate was 16.2% in unvaccinated and 17.0% among vaccinated participants. Compared with no vaccine exposure, influenza vaccination was not associated with increased rate of miscarriage when administered before (HR 0.99, 95% CI 0.81–1.20) or during (HR 0.83, 95% CI 0.47–1.47) pregnancy. Of the 1,135 couples with male partner vaccination data available, 10.8% reported vaccination less than 3 months before pregnancy. The HR for the association between male partner vaccination and miscarriage was 1.17 (95% CI 0.73–1.90). CONCLUSION: Influenza vaccination before or during pregnancy was not associated with miscarriage....

SARS-CoV-2 has been proposed to encode ORF10 as the 3' terminal gene in the viral genome. However, the potential role and even existence of a functional ORF10 product has been the subject of debate. There are significant structural features in the viral genomic RNA that could, by themselves, explain the retention of the ORF10 nucleotide sequences without the need for a functional protein product. To explore this question further we made two recombinant viruses, firstly a control virus (WT) based on the genome sequence of the original Wuhan isolate and with the inclusion of the early D614G mutation in the Spike protein. We also made a second virus, identical to WT except for two additional changes that replaced the initiating ORF10 start codon and an internal methionine codon for stop codons (ORF10KO). Here we show that the two viruses have apparently identical growth kinetics in a VeroE6 cell line that over expresses TMPRSS2 (VTN cells). However, in A549 cells over expressing ACE2 and TMPRSS2 (A549-AT cells) the ORF10KO virus appears to have a small growth rate advantage. Growth competition experiments were used whereby the two viruses were mixed, passaged in either VTN or A549-AT cells and the resulting output virus was sequenced. We found that in VTN cells the WT virus quickly dominated whereas in the A549-AT cells the ORF10KO virus dominated. We then used a hamster model of SARS-CoV-2 infection and determined that the ORF10KO virus has attenuated pathogenicity (as measured by weight loss). We found an almost 10-fold reduction in viral titre in the lower respiratory tract for ORF10KO vs WT. In contrast, the WT and ORF10KO viruses had similar titres in the upper respiratory tract. Sequencing of viral RNA in the lungs of hamsters infected with ORF10KO virus revealed that this virus frequently reverts to WT. Our data suggests that the retention of a functional ORF10 sequence is highly desirable for SARS-CoV-2 infection of hamsters and affects the virus's ability to propagate in the lower respiratory tract. ### Competing Interest Statement The authors have declared no competing interest.

Background: As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections. Methods: We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups. Results: From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 to 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 to 0.84) in October 2020 to 1.64 (95% CI: 1.33 to 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic. Conclusion: Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project was sponsored by an award from the National COVID Cohort Collaborative's Public Health Answers to Speed Tractable Results (PHASTR) program and the National Center for Advancing Translational Sciences (Award #NCATS-P00438-E-2). ### 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 design was exempted from human subjects research review by the American Academy of Family Medicine institutional review board. 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 Data are available online through the National COVID Cohort Collaborative (https://ncats.nih.gov/n3c) with signed data use agreement and project approval.

Covid 19 data NYC

Nature Communications - Here, Dias de Melo et al. assess the clinical, olfactory, and neuroinflammatory conditions of golden hamsters infected with SARS-CoV-2 wt and VOCs and report that viruses...

Nature Microbiology - Hi-C 3.0 and ChIP-seq show that SARS-CoV-2 infection alters the host cell 3D genome structure and epigenome.

npj Vaccines - Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants

covSPECTRUM is an interactive platform aiming to help scientists investigate and identify variants of SARS-CoV-2.

Correspondence from The New England Journal of Medicine — SARS-CoV-2 — No Increased Islet Autoimmunity or Type 1 Diabetes in Teens

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations. ### Competing Interest Statement MJP reports consulting fees for Gilead Sciences and AstraZeneca, outside the submitted work. TJH reports consulting fees for Roche and Regeneron outside the submitted work. ### Funding Statement PET-imaging and peripheral blood immune testing was supported by a Merck Investigator Studies Program Grant (to TJH). PET-imaging Gut biopsy collection and testing was supported by grants from the PolyBio Research Foundation (to TJH, HV and MJP). This work was also supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, K23AI157875, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine. ### 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 was approved by the University of California, San Francisco Institutional Review Board. 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 All data produced in the present study are available upon reasonable request to the authors

It is becoming increasingly apparent that EG.5.1 variant is a bit more dangerous than prior variants, if not much more dangerous. The hospitalizations have bottomed out and starting to increase in the U.S. and the U.K. as Japan is seeing exponential growth of hospitalized patients.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.

Download scientific diagram | Signs and symptoms* at hospital admission among symptomatic hospitalized pregnant women with COVID-19, † by pregnancy trimester -COVID-NET, 13 states, § March 1-August 22, 2020 from publication: Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020 | Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that... | COVID-19, Pregnant Women and Hospitality | ResearchGate, the professional network for scientists.

Whether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RN…

Die Spezialisten vom Long-Covid Netzwerk Solothurn untersuchen Long-Covid Betroffene, schliessen andere Diagnosen aus und behandeln nach aktuellen Leitlinien und neuesten wissenschaftlichen Erkenntnisse essen, koordiniert durch die Neuropraxis Solothurn.

It is undisputed that anti-SARS-CoV-2 vaccines can have side effects. Long post-COVID vaccination syndrome (LPCVS) is one of them and is often neglected. It persists 11 months after the third mRNA-1273 (Moderna) vaccine dose has not been reported. Our ...

Nature - The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.

Cognitive deficits following SARS-CoV-2 infection were detectable nearly two years post infection, and largest for individuals with longer symptom durations, ongoing symptoms, and/or more severe infection. However, no such deficits were detected in individuals who reported full recovery from COVID-19. Further work is needed to monitor and develop understanding of recovery mechanisms for those with ongoing symptoms.

Nature Reviews Immunology - SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore...

Metrics are increasing, but excess deaths are down.

Nature Reviews Immunology - SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore...

Recent analyses show that the Omicron variants of SARS-CoV-2 more strongly suppress important immune markers than previous versions of the virus.

148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported ‘breakthrough infection’ compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a ‘breakthrough infection’ compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules.

Our data provide a comprehensive overview of the longitudinal viral and antibody dynamics of omicron variant in people with acute SARS-CoV-2 infection, with important implications for public health strategies, including population screening, antiviral treatment, isolation periods, and vaccination.

Hyattsville/Maryland – In den USA werden immer wieder Long-COVID-Symptome in den Sterbeurkunden erwähnt. Mitarbeiter des National Center for Health Statistics... #COVID19

It's been linked to brain fog, dementia, stroke, and more.

We aimed to explore whether variants of SARS-CoV-2 (Chinese-derived strain (D614, lineage A), Italian strain PV10734 (D614G, lineage B.1.1) and Alpha strain (lineage B.1.1.7)) were able to infect monocytes (MN) and monocyte-derived macrophages (MDM) and ...

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