Covid19-Sources

Signal Transduction and Targeted Therapy - Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients

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To design effective vaccines and other immune interventions against a pathogen, it is necessary to know which aspect of immunity associates with protection. We investigated whether neutralizing antibodies associate with infection clearance in long-term SARS-CoV-2 infection during HIV-mediated immunosuppression. We monitored neutralizing antibody activity against SARS-CoV-2 over 1 to 2 years in five participants with advanced HIV disease and delayed control of HIV viremia. These participants had persistent SARS-CoV-2 infection ranging from 110 to 289 days which was associated with low or undetectable neutralizing antibody responses. SARS-CoV-2 clearance was associated with the emergence of neutralizing antibodies and occurred in two participants before suppression of HIV viremia, but after some CD4 T cell reconstitution. Vaccination only further increased neutralizing antibody levels in the advanced HIV disease participants who achieved HIV suppression pre-vaccination. During the prolonged SARS-CoV-2 infection we observed widespread evolution which was particularly pronounced in one Delta variant infection. This resulted in high-level escape from Delta-elicited neutralizing antibodies and a virus antigenically distinct from both ancestral SARS-CoV-2 and Omicron XBB in hamster experimental infections. The results offer new evidence that neutralizing antibodies associate with SARS-CoV-2 clearance and argue that successful management of HIV may be necessary to curtail long-term infection and evolution of co-infecting pathogens. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Bill and Melinda Gates award INV-018944 (AS), Wellcome Trust Award 226137/Z/22/Z (AS and PLM) and the South African Medical Research Council (AS and PLM). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### 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: All blood samples used for neutralization studies, nasopharyngeal swabs from the advanced HIV disease participants for outgrowth and sequencing, as well as nasopharyngeal swabs for isolation of the ancestral/D614G, Beta, and Delta virus were obtained after written informed consent from adults with PCR-confirmed SARS-CoV-2 infection enrolled in a prospective cohort of SARS-CoV-2 infected individuals at the Africa Health Research Institute approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001275/2020). The Omicron/BA.1 virus was isolated from residual swab used for diagnostic testing (Witwatersrand Human Research Ethics Committee reference M210752). The nasopharyngeal swab for isolation of the Omicron XBB.1.5 subvariant was collected after written informed consent as part of the COVID-19 transmission and natural history in KwaZulu- Natal, South Africa: Epidemiological Investigation to Guide Prevention and Clinical Care in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) study and approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001195/2020, BREC/00003106/2021). 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 work are contained in the manuscript

Es halten sich hartnäckig Mutmaßungen, dass beim Einsatz von Paxlovid zur Behandlung von Covid-19 mit einem Rebound zu rechnen sei. Ob das so st...

Since vaccination adherence is crucial in reducing morbidity and mortality during a pandemic, we characterized the association between demographic, in…

Base case results suggest the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to No Vaccine, yielding an ICER of $7,700 per QALY gained. Using a societal cost perspective, the ICER is $2,100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates and costs drive cost-effectiveness. With a relative vaccine effectiveness (rVE) of Moderna versus Pfizer-BioNTech of 5.1% for infection and 9.8% for hospitalization, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3,300 more deaths than the Pfizer-BioNTech vaccine.

This study used a population-based individual patient data set that included diagnoses of COVID-19 to determine whether there was a temporal association between COVID-19 and type 1 diabetes in children.

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Screening hospitalized COVID-19 patients for cancer could potentially save lives, a new study suggests.

Die neue "Pirola"-Variante besorgt nun auch die israelischen Behörden. Sie ordneten jetzt eine neue Testpflicht an.

In diesem ePaper widmet sich das BARMER Institut für Gesundheitssystemforschung (bifg) der Untersuchung der Übersterblichkeit in den Pandemi ..

We analyzed the kinetics and durability of the humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination using 8,000 longitudinal samples collected over a three-year period (April 2020 – April 2023) in the New York City metropolitan area. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state levels compared to naïve individuals. Antibody durability was characterized by two phases: an initial rapid decay, followed by a phase of stabilization with very slow decay resulting in an individual spike binding antibody steady state. Booster vaccination equalized the differences in antibody levels between participants with and without hybrid immunity, but the antibody titers reached decreased with each successive antigen exposure. Break-through infections increased antibody titers to similar levels as an additional vaccine dose in naïve individuals. Our study provides strong evidence for the fact that SARS-CoV-2 antibody responses are long lasting, with an initial waning phase followed by a stabilization phase.

This cohort study analyzes rates of hospital-onset SARS-CoV-2 infections and their association with hospital-level characteristics and testing practices.

Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not. Importance Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.

In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.

In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.

U.S. media has extensively covered racial disparities in COVID-19 infections and deaths, which may ironically reduce public concern about COVID-19. In…

Background  Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died ...

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.

Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections 1,2 . Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction 3–5 . The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative6,7 to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity6 , lung function 8 , and cancers 9 , suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.

Nature - A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory...

Nature Communications - Measuring an individual’s level of exposure to COVID-19 is challenging, and it is therefore unclear whether high exposure may impact immunity. Here, the authors...

4 Laryngoscope, 133:2357-2361, 2023.

Lingering COVID virus in taste buds can affect sense of taste up to 1.5 years after infection.

Wir haben zur Zeit wie jeden Spätsommer hohe Wachstumsrate bei noch relativ niedriger Inzidenz. Sars-Cov-2 will man nicht haben: Man stirbt zwar heute nicht mehr sofort daran, aber es kann sehr una…

Nature Medicine - Longitudinal proteomic profiling of over 1,800 patients revealed two distinct profiles of blood biomarkers measured on admission to hospital for COVID-19, which predict cognitive...

Nature Medicine - Longitudinal proteomic profiling of over 1,800 patients revealed two distinct profiles of blood biomarkers measured on admission to hospital for COVID-19, which predict cognitive...

An increasing number of reports suggest an association between COVID-19 infection and initiation or acceleration of neurodegenerative diseases including Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Both these diseases and several other neurodegenerative diseases are caused by conversion of human proteins into a misfolded, aggregated amyloid fibril state. The fibril formation process is self-perpetuating by seeded conversion from preformed fibril seeds. We recently described a plausible mechanism for amyloid fibril formation of SARS-CoV-2 spike protein. Spike-protein formed amyloid fibrils upon cleavage by neutrophil elastase, abundant in the inflammatory response to COVID-19 infection. We here provide evidence of significant Spike-amyloid fibril seeded acceleration of amyloid formation of CJD associated human prion protein (HuPrP) using an in vitro conversion assay. By seeding the HuPrP conversion assay with other in vitro generated disease associated amyloid fibrils we demonstrate that this is not a general effect but a specific feature of spike-amyloid fibrils. We also showed that the amyloid fibril formation of AD associated Aβ1-42 was accelerated by Spike-amyloid fibril seeds. Of seven different 20-amino acid long peptides, Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most efficient in seeding HuPrP and Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, suggesting substrate dependent selectivity of the cross-seeding activity. Albeit purely in vitro, our data suggest that cross-seeding by Spike-amyloid fibrils can be implicated in the increasing number of reports of CJD, AD, and possibly other neurodegenerative diseases in the wake of COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

Nice paper from Nature asking why T cells so often overlooked (harder to measure) & how they are the key to fighting COVID (of note, we know in HIV how important T cells are because HIV infects T cells so we think of them all the time)https://t.co/22FQv7scRg— Monica Gandhi MD, MPH (@MonicaGandhi9) February 2, 2022