Covid19-Sources

BACKGROUND: COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post–COVID-19 are not known. METHODS: Data from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score—matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components. RESULTS: The risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94–2.25]; P

Millions worldwide are living with long COVID. Since therapeutic research is ongoing, long COVID prevention is a pragmatic public health strategy. While prior analyses have shown the benefit of primary vaccination, the effect of booster vaccination on preventing long COVID caused by an Omicron infection has not been fully investigated. This systematic review identified 31 observational studies, among which 11 were deemed suitable for pairwise meta-analyses. Herein, the pooled risk of long COVID was 22–29% ( P

—about 20% reduced by primary series (vs no vaccination), and —another 20% reduction by boosters vs primary series — Eric Topol (@EricTopol)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to infect the human brain and a subset of human neurons in vitro. We have previously demonstrated that the virus enters the human induced pluripotent stem cell (hiPSC)-derived neurons via an endosomal-lysosomal pathway, which is dependent on low levels of angiotensin-converting enzyme 2 (ACE2) and independent of transmembrane serine protease 2 (TMPRSS2). Here, we use hiPSC-derived neurons overexpressing ACE2 in co-culture with human astrocytes to show that the infection with both SARS-CoV-2 Wuhan and Omicron XBB.1.5 variants is dependent on cathepsins and can be efficiently blocked by an inhibitor of cathepsin B (CA-074-ME). The result was reproducible in non-transgenic hiPSC-derived cortical organoids. The cathepsin L inhibitor SB412515 was less effective against the Wuhan strain but equally effective against the Omicron variant. Using PCR and reinfection assays, we show that SARS-CoV-2 can replicate in neurons in 2D co-cultures. Interestingly, the infectivity of the newly produced virions declined at 24 hours post-infection despite a further increase in released viral RNA at later time points, suggesting the possible activation of an antiviral response in neurons and/or astrocytes, which is supported by a correspondent increase in the levels of secreted cytokines. Furthermore, the number of infected neurons decreased within five days, suggesting that SARS-CoV-2 infection eventually leads to the death of the target neuronal cell in vitro. The infection also caused the accumulation of the hypoxia-inducible stress factor HIF1-alpha in infected neurons under normoxia. Finally, we confirm and expand the previous finding that in SARS-CoV-2 infected neurons, the microtubule-associated protein tau is hyperphosphorylated at multiple loci, including S202/T205, and mislocalized to the soma of the infected neurons. Hyperphosphorylation and mislocalization of tau are hallmarks of Alzheimer's disease (AD) and other tauopathies. Our data provides further evidence supporting the neurodegenerative potential of SARS-CoV-2 infection. ### Competing Interest Statement The authors have declared no competing interest.

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal ...

npj Viruses - Reduced cross-protective potential of Omicron compared to ancestral SARS-CoV-2 spike vaccines against potentially zoonotic coronaviruses

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to infect the human brain and a subset of human neurons in vitro. We have previously demonstrated that the virus enters the human induced pluripotent stem cell (hiPSC)-derived neurons via an endosomal-lysosomal pathway, which is dependent on low levels of angiotensin-converting enzyme 2 (ACE2) and independent of transmembrane serine protease 2 (TMPRSS2). Here, we use hiPSC-derived neurons overexpressing ACE2 in co-culture with human astrocytes to show that the infection with both SARS-CoV-2 Wuhan and Omicron XBB.1.5 variants is dependent on cathepsins and can be efficiently blocked by an inhibitor of cathepsin B (CA-074-ME). The result was reproducible in non-transgenic hiPSC-derived cortical organoids. The cathepsin L inhibitor SB412515 was less effective against the Wuhan strain but equally effective against the Omicron variant. Using PCR and reinfection assays, we show that SARS-CoV-2 can replicate in neurons in 2D co-cultures. Interestingly, the infectivity of the newly produced virions declined at 24 hours post-infection despite a further increase in released viral RNA at later time points, suggesting the possible activation of an antiviral response in neurons and/or astrocytes, which is supported by a correspondent increase in the levels of secreted cytokines. Furthermore, the number of infected neurons decreased within five days, suggesting that SARS-CoV-2 infection eventually leads to the death of the target neuronal cell in vitro. The infection also caused the accumulation of the hypoxia-inducible stress factor HIF1-alpha in infected neurons under normoxia. Finally, we confirm and expand the previous finding that in SARS-CoV-2 infected neurons, the microtubule-associated protein tau is hyperphosphorylated at multiple loci, including S202/T205, and mislocalized to the soma of the infected neurons. Hyperphosphorylation and mislocalization of tau are hallmarks of Alzheimer's disease (AD) and other tauopathies. Our data provides further evidence supporting the neurodegenerative potential of SARS-CoV-2 infection. ### Competing Interest Statement The authors have declared no competing interest.

Introduction Long coronavirus disease (COVID) poses a significant burden following the coronavirus disease 2019 (COVID-19) pandemic. Debate persists regarding the impact of nonsteroidal anti-inflammatory drug (NSAID) administration during acute-phase COVID-19 on the development of long COVID. Hence, this study aimed to assess the potential association between NSAID use and long COVID using data from patients with COVID-19 in Korea’s National Health Insurance Service. Methods This nested case-control study defined the study cohort as patients diagnosed with COVID-19 for the first time between 2020 and 2021. The primary exposure investigated was NSAID prescriptions within 14 days of the initial COVID-19 diagnosis. We used propensity score matching to create three control patients matched to each patient in the NSAID exposure group. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after the adjustment for demographics, Charlson Comorbidity Index, and existing comorbidities. Results Among the 225,458 patients diagnosed with COVID-19, we analyzed data from 254 with long COVID. The adjusted OR (aOR) for NSAID exposure during acute-phase COVID-19 was higher in long COVID cases versus controls (aOR, 1.79; 95% CI, 1.00–3.19), suggesting a potential relationship. However, a sensitivity analysis revealed that the increased odds of NSAID exposure in the acute phase became statistically non-significant (aOR, 1.64; 95% CI, 0.90–2.99) when COVID-19 self-quarantine duration was included as a covariate. Additionally, acetaminophen exposure was not significantly associated (aOR, 1.12; 95% CI, 0.75–1.68), while antiviral drugs demonstrated a stronger association (aOR, 3.75; 95% CI, 1.66–8.48). Conclusion Although this study suggests a possible link between NSAID use in the acute COVID-19 infection stage and a higher risk of long COVID as well as both NSAID and acetaminophen use during the chronic COVID-19 period and a lower risk of long COVID, the association was not statistically significant. Further research is needed to determine the causal relationship between the various treatment options for acute COVID-19 and the development of long COVID.

Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management.

Background Studies on occupation and COVID-19 infection that cover a range of occupational groups and adjust for important confounders are lacking. This study aimed to estimate occupational risks of hospitalization with COVID-19 by taking into account sociodemographic factors and previous comorbidities. Methods We applied a case-cohort design using workers insured with one of Germany’s largest statutory health insurers as a data source for occupational and demographical information as well as for information on comorbidities. Cox regression models with denominator weights for cases and controls assessed relative risks of hospitalization with COVID-19 in 2020. Results The study consisted of 11,202 COVID-19 cases and 249,707 non-cases. After adjusting for age, sex, number of pre-existing comorbidities, and socioeconomic status, we found at least doubled risks for occupations in theology and church work (HR = 3.05; 95% CI 1.93–4.82), occupations in healthcare (HR = 2.74; 95% CI 2.46–3.05), for bus and tram divers (HR = 2.46; 95% CI 2.04–2.97), occupations in meat processing (HR = 2.16; 95% CI 1.57–2.98), and professional drivers in passenger transport (e.g. taxi drivers) (HR = 2.00; 95% CI 1.59–2.51). In addition, occupations in property marketing and management, social workers, laboratory workers, occupations in personal care (e.g. hairdressers), occupations in housekeeping and occupations in gastronomy all had statistically significantly increased risks compared to the reference population (administrative workers). Conclusions We identified occupations with increased risks for hospitalization with COVID-19. For those having a doubled risk it can be assumed that COVID-19 diseases are predominantly occupationally related. By identifying high-risk occupations in non-healthcare professions, effective measures to prevent infections in the workplace can be developed, also in case of a future pandemic.

As we approach the five year mark of the first known case of covid-19, as we contemplate a half decade of watching a novel virus rip through our communities, our countries, our world, I wanted to do a retrospective on the pandemic.

@DrGrahamLJ: Here's a reminder of my take on #COVID-19 (the disease not the pandemic). It's not what you think it is ... A thread 👇 1/23 The acute phase of #COVID was and is misunderstood by...

There is a person from Anne Arundel county that has been infected with SARS-CoV-2 for about 3 years (Delta infection). They probably don’t even know they are infected, but they are shedding a ton of viral material in wastewater 1/ — Marc Johnson (@SolidEvidence)

It carried a key mutation: PB2 E627K. Now, H5N1 is showing signs of similar adaptation. The strain detected in a Canadian teenager also carries PB2 E627K. 1/ — Outbreak Updates (@outbreakupdates)

Understanding the evolutionary events that led to SARS-CoV-2 emergence, spillover, and spread is crucial to prevent, or at least be prepared for, the same type of occurrence in the future. Given that SARS-CoV-2 has some characteristics not found in other ...

Scientific Reports - Long COVID prevalence and impact on quality of life 2 years after acute COVID-19

Non-pharmaceutical public health measures (PHMs) were central to pre-vaccination efforts to reduce Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) exposure risk; heterogeneity in adherence placed bounds on their potential effectiveness, and correlation in their adoption makes assessing the impact attributable to an individual PHM difficult. During the Fall 2020 semester, we used a longitudinal cohort design in a university student population to conduct a behavioral survey of intention to adhere to PHMs, paired with an IgG serosurvey to quantify SARS-CoV-2 exposure at the end of the semester. Using Latent Class Analysis on behavioral survey responses, we identified three distinct groups among the 673 students with IgG samples: 256 (38.04%) students were in the most adherent group, intending to follow all guidelines, 306 (46.21%) in the moderately-adherent group, and 111 (15.75%) in the least-adherent group, rarely intending to follow any measure, with adherence negatively correlated with seropositivity of 25.4%, 32.2% and 37.7%, respectively. Moving all individuals in an SIR model into the most adherent group resulted in a 76-93% reduction in seroprevalence, dependent on assumed assortativity. The potential impact of increasing PHM adherence was limited by the substantial exposure risk in the large proportion of students already following all PHMs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from the Office of the Provost and the Clinical and Translational Science Institute, Huck Life Sciences Institute, and Social Science Research Institutes at the Pennsylvania State University. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR002014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding sources had no role in the collection, analysis, interpretation, or writing of the report. ### 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: IRB of Pennsylvania State University gave ethical approval for this work 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 The datasets generated during and/or analyzed during the current study are not publicly available as they contain personally identifiable information, but are available from the corresponding author on reasonable request.

Molecular Psychiatry - Maternal COVID-19 infection associated with offspring neurodevelopmental disorders

Rare clinical evidence from a massive COVID-19 surge in China reveals that maternal SARS-CoV-2 infection during gestational weeks 4–6 is significantly associated with fetal situs inversus. This observation illustrates previously unknown consequences of SARS-CoV-2 exposure in pregnancy and links human visceral lateralization with a specific fetal development stage.

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Abstract: The long-term consequences of COVID-19 infection are becoming increasingly evident in recent studies. This repeated cross-sectional study aimed to explore the long-term health and cognitive effects of COVID-19, focusing on how virus variants, vaccination, illness severity, and time since infection impact post-COVID-19 outcomes. We examined three cohorts of university students (N=584) and used non-parametric methods to assess correlations of various health and cognitive variables with SARS-CoV-2 infection, COVID-19 severity, vaccination status, time since infection, time since vaccination, and virus variants. Our results show that some health and cognitive impairments persist, with some even progressively worsening especially fatigue in women and memory in men, up to four years post-infection, with the Wuhan variant having the most significant long-term impact and the Omicron variant the least. Interestingly, the severity of the acute illness was not correlated with the variant of SARS-CoV-2. The analysis also revealed that individuals who contracted COVID-19 after vaccination had better health and cognitive outcomes compared to those infected before vaccination. The study also discusses some limitations inherent in cross-sectional studies, particularly those arising from the stronger tendency of individuals with poorer health, compared to healthier individuals, to avoid infection and prioritize vaccination. To mitigate potential bias, the study proposes focusing on factors such as illness severity and time since infection or vaccination when analyzing persistent symptoms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by the Czech Science Foundation, grant number 22-20785S. ### 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: Institutional Review Board of the Faculty of Science at Charles University gave ethical approval for this work (No. 2021/19) 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 are available online at Figshare 10.6084/m9.figshare.27618876

A COVID-era surge in the death rate has shaved months off the life expectancy of Australians, who remain among the longest-lived people in the world.

Nasal IgA1 autoantibodies against IFN-α are associated with better COVID-19 prognosis, including fewer symptoms and robust anti–SARS-CoV-2 immunity.

Signal Transduction and Targeted Therapy - A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2

Post-COVID-19 conditions have emerged as a global health challenge. This study examined the long-term effects of COVID-19 vaccination on the incidence…

This randomized clinical trial compares reactogenicity, safety, and short-term health-related quality-of-life outcomes after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 and influenza vaccines.

The emergence of SARS-CoV-2 variants poses ongoing challenges to vaccine efficacy. We evaluated neutralizing antibody responses against JN.1 and its derivatives (KP.3, KP.3.1.1, LB.1, and XEC) in healthcare workers who received seven doses of BNT162b2, including XBB.1.5 monovalent vaccine. In COVID-19-naive individuals, KP.3.1.1 and LB.1 showed substantial immune escape, while previously infected individuals maintained neutralization activity against all variants. We also demonstrated that JN.1-based immunization induces robust cross-neutralizing activity against emerging variants. A single amino acid deletion at position 31 in the spike protein significantly impacted immune evasion. These findings support the potential effectiveness of JN.1-based vaccines while highlighting the need for continued surveillance and vaccine optimization. ### Competing Interest Statement The authors have declared no competing interest.

GeroScience - Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30–40% experience persistent...

Für bestimmte Personengruppen kann eine Corona-Impfung weiterhin lebensrettend sein. Nun hat die US-Gesundheitsbehörde neue Empfehlungen, wie oft sie stattfinden sollte.