Covid19-Sources

COVID-19 pathology is associated with concerted inhibition of mitochondrial gene expression in mammalian hosts.

Chronic fatigue is a debilitating symptom that affects many individuals, but its mechanism remains poorly understood. This study shows that endoplamic reticulum (ER) stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance. Alleviating ER stress decreases WASF3 and restores mitochondrial function, indicating that WASF3 can impair skeletal muscle bioenergetics and may be targetable for treating fatigue symptoms. Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), here identified in a 38-y-old woman suffering from long-standing fatigue and exercise intolerance, can disrupt mitochondrial respiratory supercomplex formation and is associated with endoplasmic reticulum (ER) stress. Increased expression of WASF3 in transgenic mice markedly decreased their treadmill running capacity with concomitantly impaired respiratory supercomplex assembly and reduced complex IV levels in skeletal muscle mitochondria. WASF3 induction by ER stress using endotoxin, well known to be associated with fatigue in humans, also decreased skeletal muscle complex IV levels in mice, while decreasing WASF3 levels by pharmacologic inhibition of ER stress improved mitochondrial function in the cells of the patient with chronic fatigue. Expanding on our findings, skeletal muscle biopsy samples obtained from a cohort of patients with ME/CFS showed increased WASF3 protein levels and aberrant ER stress activation. In addition to revealing a potential mechanism for the bioenergetic deficiency in ME/CFS, our study may also provide insights into other disorders associated with fatigue such as rheumatic diseases and long COVID.

The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore …

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Von jeher kenne ich Diskussionen mit Patienten über die Sinnhaftigkeit von präventiven Untersuchungen, von Medikamenten, Impfungen oder über deren potenzielle Nebenwirkungen. Immer schon gab es den „Tennistrainer von der Cousine der Postbotin“, der ganz sicher aufgrund des Medikamentes xy einen qualvollen Tod erlitt. Und ja, es gab auch schon immer tatsächlich aufgetretene Nebenwirkungen. Denn alles, was wirkt, kann auch Nebenwirkungen haben.

Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 r …

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and “brain fog” are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.

AbstractContext. Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased.Objective. To compare the incidence of idiopat

We explain how coronavirus progresses in the body, including how it can affect your heart and circulatory system.

Metaanalyse stellt das Fehlen eines Zusammenhangs zwischen der #COVID19-Impfung und einem erhöhten Risiko für die Gesamtmortalität fest.Bekannter Desinformationskünstler betont den Anstieg kardinaler Todesfälle, lässt aber wieder mal entscheidende Details weg.🧵⬇️1/10 pic.twitter.com/XwAmDrgaJf— 𝘒𝘢𝘵𝘩𝘳𝘪𝘯 𝘌♭ 🎶 (@Musician1980) August 5, 2023

Joseph Ladapo defended the move, saying revisions are a normal part of assessing such analysis.

Edition 154

The South-West of England has seen a surge in Covid cases and hospital admissions

Nate Bear published a post on Ko-fi

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.