High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains
Acta Neuropathologica - The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine...
SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids
Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 ant…
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future.
Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health
GeroScience - Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of...
Driving Under the Cognitive Influence of COVID-19: Exploring the Impact of Acute SARS-CoV-2 Infection on Road Safety
This study evaluated the association between acute COVID-19 cases and the number of car crashes with varying COVID-19 vaccination rates, Long COVID rates, and COVID-19 mitigation strategies.
Background
The ongoing SARS-CoV-2 pandemic has led to significant concern over long-term post-infection sequelae, especially in the Neurologic domain. Long COVID symptoms, including cognitive impairments, could potentially impact activities requiring high cognitive function, such as driving. Despite various potential impacts on driving skills and the general prevalence of Long COVID, the specific effects on driving capabilities remain understudied.
Design/Methods
This study utilized a Poisson regression model to analyze data from 2020-2022, comparing aggregate car crash records and COVID-19 statistics. This model adjusted for population and included binary variables for specific months to account for stay-at-home orders. The correlation between acute COVID-19 cases and car crashes was investigated across seven states, considering vaccination rates and COVID-19 mitigation measures as potential confounders.
Results
Findings indicate an association between acute COVID-19 rates and increased car crashes with an OR of 1.5 (1.23-1.26 95%CI). The analysis did not find a protective effect of vaccination against increased crash risks, contrary to previous assumptions. The OR of car crashes associated with COVID-19 was comparable to driving under the influence of alcohol at legal limits or driving with a seizure disorder.
Conclusions
The study suggests that acute COVID-19, regardless of Long COVID status, is linked to an increased risk of car crashes presumably due to neurologic changes caused by SARS-CoV-2. These findings underscore the need for further research into the neuropsychological impacts of COVID-19. Further studies are recommended to explore the causality and mechanisms behind these findings and to evaluate the implications for public safety in other critical operational tasks. Finally, neurologists dealing with post-COVID patients, should remember that they may have an obligation to report medically impaired drivers.
Aerosol research shows how easily COVID-19 can be caught through the air
The virus winter season has struck—and COVID-19 is still part of everyday life. However, unlike during the pandemic, we now know more about how it spreads through the air we breathe. Research from Lund ...
Immune system damage from COVID-19 is different from HIV/AIDS — but the advocacy has parallels - The Sick Times
Lymphopenia is a health condition in which people have low white blood cell count in their blood. Without these cells, the body is unable to defend itself effectively against pathogens. Lymphopenia is one type of way your body can be immunocompromised; it can be caused by many things, including infections, inherited conditions, autoimmune disorders, and nutritional deficiencies. Earlier in the pandemic, scientists learned that some patients can develop lymphopenia from SARS-CoV-2 infection — but there’s been little research into it since. Although this condition is more rarely seen in COVID-19 as compared to HIV/AIDS, some advocates have suggested the two diseases are similar in their damage to the immune system.
How the virus behind COVID-19 can harm your blood vessels and your heart
Researchers are zeroing in on the ways SARS-CoV-2 damages and persists inside blood vessels, raising the risk for heart attacks and strokes years after an initial infection.
Nucleocapsid Antibodies as an Optimal Serological Marker of SARS‐CoV‐2 Infection: A Longitudinal Study at the Thomayer University Hospital
The study reveals the diagnostic significance of nucleocapsid antibodies and the strategy for testing past COVID-19 infection in the posvaccination era. The results demonstrate that hybrid immunity a...
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hPSC-derived DA neurons are susceptible to SARS-CoV-2 infection
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SARS-CoV-2 infection of DA neurons triggers cellular senescence response
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Several FDA-approved drugs were identified to rescue senescence of DA neurons
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Cellular senescence was found in substantia nigra tissues of COVID-19 patients
Summary
COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.
Elevated Atherogenicity in Long COVID: A Systematic Review and Meta-Analysis
Background Long COVID (LC) is a complex, multi-organ syndrome that persists following recovery from the acute phase of coronavirus infection. Cardiovascular involvement is frequently reported in LC, often accompanied by a spectrum of related symptoms. Dysregulated lipid profiles and elevated atherogenic indices have been implicated in LC, yet no comprehensive systematic review and meta-analysis has specifically addressed these biomarkers.
Objective This study aims to systematically evaluate atherogenic indices and lipid-related biomarkers in individuals with LC compared to healthy controls.
Methods A systematic search was conducted in databases including PubMed, Google Scholar, SCOPUS, and SciFinder from September to November 2024. Eligible studies reported lipid biomarker data for LC patients and controls, yielding 44 studies encompassing 8,114 participants (3,353 LC patients and 4,761 controls).
Results LC patients exhibited significant elevations in Castelli Risk Indexes 1 (standardized mean difference, SMD = 0.199; 95% confidence intervals, CI: 0.087–0.312) and 2 (SMD = 0.202; 95% CI: 0.087–0.318). Atherogenic ratios, including triglyceride (TG)/high-density lipoprotein (HDL) (SMD = 0.294; 95% CI: 0.155–0.433), (TG + low-density lipoprotein, LDL + very low-density lipoprotein, VLDL)/(HDL + apolipoprotein, ApoA) (SMD = 0.264; 95% CI: 0.145–0.383), and ApoB/ApoA (SMD = 0.515; 95% CI: 0.233–0.796), were also significantly elevated. Additionally, LC patients demonstrated increased levels of LDL, total cholesterol, triglycerides, and ApoB, alongside reduced HDL and ApoA levels. Results were free from publication bias.
Conclusion LC is associated with a pro-atherogenic lipid profile, marked by increased atherogenic components and decreased protective lipid biomarkers. These findings highlight a potential heightened risk for cardiovascular complications in LC patients, warranting further clinical and mechanistic investigations.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
The study was funded by FF66 grant and a Sompoch Endowment Fund (Faculty of Medicine), MDCU (RA66/016) to MM, and Grant № BGRRP2.0040007„01Strategic Research and Innovation Program for the Development of MU PLOVDIV (SRIPD MUP), Creation of a network of research higher schools, National plan forrecovery and sustainability, European Union NextGenerationEU.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
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 corresponding author (MM) will consider reasonable requests for access to the dataset (Excel file) utilized in this meta-analysis, following the completion of data usage by all contributing authors.
Wie eine Corona-Infektion Blutzellen langfristig verändert
Mithilfe der Echtzeit-Verformungszytometrie konnten Forschende des Max-Planck-Zentrums für Physik und Medizin und der FAU erstmals zeigen: Durch eine Covid-19-Erkrankung verändern sich Größe und…
Mitigating the risks of post-acute sequelae of SARS-CoV-2 infection (PASC) with intranasal chlorpheniramine: perspectives from the ACCROS studies
The World Health Organization (WHO) declared the end of the COVID-19 (SARS-CoV-2) global public
health emergency on May 5, 2023, but its long-term consequences have still been haunting the global population.
Post-acute sequelae of COVID-19 (PASC) and long-term COVID-19 are serious concerns and present with various
symptoms. Intranasal chlorpheniramine (iCPM) has been shown to decrease the viral burden of SARS-COV-2.
iCPM uses decreased COVID-19 disease progression and severity in Accelerating COVID-19 Clinical Recovery in an
Outpatient Setting (ACROSS)-I & III randomized control trials (RCT).
Methods This prospective survey study included 259 participants in ACROSS I and III RCTs. We compared the effect
of iCPM versus placebo on the reduction of PASC symptoms. A PASC questionnaire containing 17 questions regarding
the most common PASC symptoms was used in this study. T-test and Pearson chi-square statistics were performed
according to continuous and categorical data using STATA 17.0 Basic Edition software.
Findings The iCPM cohort had a lower proportion of patients with fatigue or tiredness vs. placebo (0 Vs 17, 21,
p 0.001). iCPM cohort had a lower proportion of patients with difficulty concentrating or mental confusion (0 vs. 22,
27, p 0.001). iCPM cohort had also a lower number of patients with difficulty in the ability to perform daily activities
or work vs. placebo (1 Vs 38, 48, p 0.001). A smaller number of patients in the iCPM cohort sought medical attention
for PACS symptoms compared to placebo (0 vs. 48, 68, p 0.001).
Interpretation The use of intranasal chlorpheniramine shows promise in preventing COVID-19 progression to the
often-debilitating post-COVID-19 syndrome PASC. The association between iCPM use and a lower prevalence of PASC
symptoms is strong. Further studies are needed to establish the role of ICPM in preventing PASC.
Keywords COVID-19, SARS-CoV-2, Intranasal chlorpheniramine, Efficacy, Randomized clinical trial, Double-blind,
Placebo-controlled clinical trial
Comparison of viral load in the nasopharyngeal swabs of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different epidem …
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly undergone mutations since its emergence, based on which it has been as …
Long COVID Breakthrough: Spike Proteins Persist in Brain for Years
Researchers have discovered that the SARS-CoV-2 spike protein persists in the brain and skull bone marrow for years after infection, potentially leading to chronic inflammation and neurodegenerative diseases. Researchers from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have uncovere
An ultra-long heavy chain bovine antibody neutralizes SARS-CoV-2 and reacts broadly with sarbecoviruses.
The threat of emergence of further SARS-CoV-2 variants, and the future spillover potential of other sarbecoviruses has prompted continued efforts to isolate broadly reactive monoclonal antibodies for therapeutic use. In this study, we generated monoclonal antibodies from immunised cattle, primarily because of their ability to produce antibodies with ultra-long heavy chain complementarity determining region 3 (CDRH3) domains. Such antibodies have been shown to have potent and cross-reactive neutralisation phenotypes in other virus infections. Following extended immunisation with different forms of spike protein and using single B-cell sorting and phage display techniques, we isolated 33 mAbs, including 10 with ultra-long CDRH3s (50 amino acids). Of these, mAbs P7 and 99 exhibited remarkable neutralisation breadth and potency. Notably, mAb P7, which possessed an ultra-long CDRH3, neutralised all tested variants, including SARS-CoV-1, with IC50 values ranging from 0.01 ug/mL to 1.06 ug/mL. This antibody was also cross-reactive against a panel of RBDs from diverse sarbecovirus species. Structural studies revealed that mAb 99 targets a region of the receptor-binding domain (RBD) of the spike protein that overlaps with the ACE2 binding site. Although the structure of the P7 Fab-RBD complex was not resolvable, data suggest P7 induces trimer dissociation by binding to an occluded RBD epitope, likely mediated by the extended CDRH3 structure. Syrian hamster challenge experiments, using several VOCs, showed that mAbs P7 and 99 significantly reduced lung viral load. These findings highlight the potential of bovine-derived, especially those possessing ultra-long CDRH3s, as effective therapeutics against current and future sarbecovirus threats.
Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers
Scientific Reports - Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers
Five years of the COVID-19 pandemic: An interview with Dr. Arijit Chakravarty
In this interview, Dr. Chakravarty discusses the current state of the COVID-19 pandemic and public health globally five years after the initial outbreak of the SARS-CoV-2 virus in Wuhan, China.
Investigation of ritonavir analogs antiretroviral natural compounds against SARS-CoV-2 envelope protein
Since the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, there has been a surge in scientific research to find a permanent cur...
Genetic Conservation and Diversity of SARS‐CoV‐2 Envelope Gene Across Variants of Concern
SARS-CoV-2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved and evolving slowly. Pan-sarbecoviruses–conserved regions in the E gene h...
Tattoo ink induces inflammation in the draining lymph node and impairs the immune response against a COVID-19 vaccine
Despite safety concerns regarding the toxicity of tattoo ink, no studies have reported the consequences of tattooing on the immune response. In this work, we have characterized the transport and accumulation of different tattoo inks in the lymphatic system using a murine model. Upon quick lymphatic drainage, we observed that macrophages mainly capture the ink in the lymph node (LN). An initial inflammatory reaction at local and systemic levels follows ink capture. Notably, the inflammatory process is maintained over time as we observed clear signs of inflammation in the draining LN two months following tattooing. In addition, the capture of ink by macrophages was associated with the induction of apoptosis in both human and murine models. Furthermore, the ink accumulated in the LN altered the immune response against a COVID-19 vaccine. We observed a reduced antibody response following vaccination with a mRNA-based SARS-CoV-2 vaccine, which was associated with a decreased expression of the Spike protein in macrophages in the draining LN. Considering the unstoppable trend of tattooing in the population, our results are crucial in informing the toxicology programs, policymakers, and the general public regarding the potential risk of the tattooing practice associated with an altered immune response. ### Competing Interest Statement The authors have declared no competing interest.
Risk Impact of SARS-CoV-2 Coronavirus and Spike Protein on Cardiac Tissue: A Comprehensive Review
The global COVID-19 pandemic, caused by SARS-CoV-2, has led to
significant morbidity and mortality, with a profound impact on
cardiovascular health. This review investigates the mechanisms of
SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing
the role of the Spike protein and ACE2 receptor in facilitating viral
entry and subsequent cardiac complications. We dissect the
structural features of the virus, its interactions with host cell
receptors, and the resulting pathophysiological changes in the heart.
Highlighting SARS-CoV-2's broad organ tropism, especially its effects
on cardiomyocytes
via ACE2 and TMPRSS2, the review addresses
how these interactions exacerbate cardiovascular issues in patients
with pre-existing conditions such as diabetes and hypertension.
Additionally, we assess both direct and indirect mechanisms of virus-
induced cardiac damage, including myocarditis, arrhythmias, and
long-term complications such as 'long COVID'. This review
underscores the complexity of SARS-CoV-2’s impact on the heart,
emphasizing the need for ongoing research to fully understand its
long-term effects on cardiovascular health.
COVID-19 pandemic reshaped seasonal patterns and age distributions of respiratory viruses
Objectives This study aims to investigate the changes in the prevalence and demographic characteristics of common respiratory viruses during and after the COVID-19 pandemic. Methods We retrospectively enrolled children with acute respiratory infections (ARIs) at Shiyan Renmin Hospital, Hubei University of Medicine, from January 2020 to December 2023. Specimens serum, nasopharyngeal aspirate, and alveolar lavage fluid were collected for direct immunofluorescence assay (DFA): respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (IAV), influenza B virus (IBV), and parainfluenza virus (PIV). Demographic data and laboratory test results were analyzed accordingly. Results A total of 10,193 patients were enrolled. The positive infection rates for the years 2020, 2021, 2022, and 2023 were 3.97%, 3.15%, 36.20%, and 38.82%, respectively. The seasonal patterns for ADV transitioned from peaking in the summer and autumn of 2022 to summer and winter in 2023, while RSV peaked in the spring and summer of 2022 but moved to spring and autumn in 2023. PIV shifted from autumn 2022 to both spring and autumn in 2023. Intriguingly, IAV stably remained a two-season pattern of summer and winter in 2022 and 2023, while IBV showed up at 2022 winter but largely diminished later. The age distribution of children infected with ADV, RSV and PIV showed an upward trend, while no significant changes were observed for IAV and IBV. Conclusions The COVID-19 pandemic has disrupted the seasonal circulation of respiratory viruses. The seasonal pattern of influenza virus has been restored in 2022. In contrast, ADV, PIV, and RSV showed significant seasonal changes after the pandemic. The increasing age distributions of cases indicates an expanded age range of infection. Continuous monitoring of pathogen distribution and adjustment of preventive strategies are crucial for the effective management of pediatric ARIs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by The Domestic Scholar Visiting Program of Wuhan University. ### 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 approved by the Ethics Committee of Shiyan Renmin Hospital, Hubei University of Medicine (File NO. SYRMYY-2024-137). 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
Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells
Inflammation - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of...