Covid19-Sources

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.

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…

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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly undergone mutations since its emergence, based on which it has been as …

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

Scientific Reports - Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis

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.

Scientific Reports - Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers

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.

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...

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...

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.

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.

Along with a baffling rise in post-pandemic mortality rates, the number of Americans claiming disabilities has skyrocketed since 2020.

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

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...

Background: Variants of concern (VOCs) have been replacing each other during the still rampant COVID-19 pandemic. As a result, SARS-CoV-2 populations have evolved increasingly intricate constellations of mutations that often enhance ...

PDF | On Jan 1, 2023, Salvatore Sciacchitano and others published AIDS and COVID-19 are two diseases separated by a common lymphocytopenia | Find, read and cite all the research you need on ResearchGate

There is uncertainty about the mode of transmission of the severe acute respiratory syndrome (SARS) virus. We analyzed the temporal and spatial distributions of cases in a large community outbreak ...

Background Neurological complications are a significant concern of Coronavirus Disease 2019 (COVID-19). However, the pathogenic mechanism of neurological symptoms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is poorly understood. Methods We used Drosophila as a model to systematically analyze SARS-CoV-2 genes encoding structural and accessory proteins and identified the membrane protein (M) that disrupted mitochondrial functions in vivo. The M protein was stereotaxically injected to further assess its effects in the brains of wild-type (WT) and 5 × FAD mice. Omics technologies, including RNA sequencing and interactome analysis, were performed to explore the mechanisms of the effects of M protein both in vitro and in vivo. Results Systematic analysis of SARS-CoV-2 structural and accessory proteins in Drosophila identified that the M protein induces mitochondrial fragmentation and dysfunction, leading to reduced ATP production, ROS overproduction, and eventually cell death in the indirect flight muscles. In WT mice, M caused hippocampal atrophy, neural apoptosis, glial activation, and mitochondrial damage. These changes were further aggravated in 5 × FAD mice. M was localized to the Golgi apparatus and genetically interacted with four wheel drive (FWD, a Drosophila homolog of mammalian PI4KIIIβ) to regulate Golgi functions in flies. Fwd RNAi, but not PI4KIIIα RNAi, reversed the M-induced Golgi abnormality, mitochondrial fragmentation, and ATP reduction. Inhibition of PI4KIIIβ activity suppressed the M-induced neuronal cell death. Therefore, M induced mitochondrial fragmentation and apoptosis likely through disruption of Golgi-derived PI(4)P-containing vesicles. Conclusions M disturbs the distribution and function of Golgi, leading to mitochondrial abnormality and eventually neurodegeneration via a PI4KIIIβ-mediated mechanism. This study reveals a potential mechanism for COVID-19 neurological symptoms and opens a new avenue for development of therapeutic strategies targeting SARS-CoV-2 M or mitochondria.

„Zunehmende Hinweise deuten auf signifikante und lang anhaltende neurologische Manifestationen von COVID-19 hin. Etwa vier von fünf Patienten, die an … — Ralf Wittenbrink (@RWittenbrink)

Nature Communications - Macrophages drive inflammation associated with severe COVID-19 but it is less clear whether they can be infected. Here, the authors show efficient antibody-mediated...

Scientific Reports - Impact of COVID-19 pandemic on acute stroke care in a tertiary stroke centre

Scientific Reports - Heart rate variability parameters indicate altered autonomic tone in subjects with COVID-19

Scientific Reports - Impact of COVID-19 on heart rate variability in post-COVID individuals compared to a control group

Scientific Reports - Assessing COVID-19 transmission through school and family networks using population-level registry data from the Netherlands

XEC and KP.3.1.1 have surpassed KP.3 to become the globally dominant lineages due to their unique NTD mutations. However, several emerging JN.1 sublineages, such as LF.7.2.1, MC.10.1, NP.1, and, especially, LP.8.1, have demonstrated superior growth advantages compared to XEC. It is critical to access the virological and antigenic characteristics of these emerging SARS-CoV-2 variants. Here, we found that LF.7.2.1 is significantly more immune invasive than XEC, primarily due to the A475V mutation, which enabled the evasion of Class 1 neutralizing antibodies. However, LF.7.2.1's weak ACE2 binding affinity substantially impaired its fitness. Likewise, MC.10.1 and NP.1 exhibited strong antibody immune evasion due to the A435S mutation, but their limited ACE2 engagement efficiency restricted their growth advantage, suggesting that A435S may regulate the Spike conformation, similar to the NTD glycosylation mutations found in KP.3.1.1 and XEC. Most importantly, we found that LP.8.1 showed comparable humoral immune evasion to XEC but demonstrated much increased ACE2 engagement efficiency, supporting its rapid growth. These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 and its descend lineages. ### Competing Interest Statement Y.C. has provisional patent applications for the BD series antibodies (WO2024131775A9 and WO2023151312A1), and is the founder of Singlomics Biopharmaceuticals. The other authors declare no competing interests.

A landmark paper[1] entitled, “Fibrin drives thrombo-inflammation and neuropathology in COVID-19,” was published in August 2024 that concluded the mechanism of the thrombotic and neurological symptoms following a SARS-CoV-2 infection, often called “long COVID,” is attributable to the binding of fibrin to discrete portions of the spike protein, specifically three N-terminal domains. This paper is a high impact publication with 110,000 views, placing it in the 99th percentile of articles published contemporaneously. Here I examine the regions of the spike protein that bind to fibrin, fibrinogen, or both. The N-terminus of the spike protein contains the three strongest binding peptides and surprisingly, these regions are also the three insertions in the protein sequence that are unique to SARS-CoV-2 and not found in natural sarbecoviruses. All pre-pandemic sarbecoviruses have either a partial deletion in these regions or have protein amino acid substitutions that are non-conserved and therefore would not support fibrin binding. In addition, the three inserts also correspond to regions of the spike protein that have been shown previously to have high sequence homology with the HIV gp120 protein. GP120 is an HIV surface protein that binds to a host cell surface receptor on CD4+ T-cells and facilitates cell entry to begin infections.  In comparing the immunological and clinical presentation of HIV and COVID-19 patients, the commonality of D-dimer production, CD4+ lymphopenia, neurotropism, and IL-10 expression strongly suggests that these protein sequence homologies are clinically relevant. A conclusion that the pathophysiology of long COVID is based on the insertion of spike protein motifs with sequence homology that mimic the HIV gp120 protein motif properties, and that these SARS-CoV-2 motifs are not found in the sarbecovirus subgenus strongly suggests that these inserts were design features in the synthetic assembly of SARS-CoV-2. [1] Ryu, J.K., Yan, Z., Montano, M. et al. Fibrin drives thromboinflammation and neuropathology in COVID-19. Nature 633, 905–913 (2024). https://doi.org/10.1038/s41586-024-07873-4

Scientific Reports - The association between baseline viral load and long-term risk in patients with COVID-19 in Hong Kong: a territory-wide study

Exposure to the virus in utero may have affected children’s development, according to a UCLA study, adding to a list of health problems emerging in the wake of the global pandemic.