Covid19-Sources

Researchers from Michigan State University and Corewell Health, in collaboration with the Cleveland Clinic, have made a significant breakthrough in understanding post-COVID-19 lung complications.

Toll-like receptor 4 (TLR4) in complex with myeloid differentiation factor 2 (MD2) plays a central role in innate immemerged as the principal interfaceune sensing and inflammatory responses during viral infections. Emerging evidence suggests that viral glycoproteins, including the SARS-CoV-2 spike (S) protein, can aberrantly activate TLR4, contributing to cytokine storms; however, the molecular basis remains unclear. In this study, we investigated the recognition of the SARS-CoV-2 spike protein, in both its monomeric and trimeric forms, by the TLR4/MD2 receptor complex using a comprehensive in silico framework. Protein–protein docking, extended molecular dynamics simulations (500 ns), interaction profiling, principal component analysis, free energy landscape mapping, and binding-affinity calculations were employed. The S1 subunit, particularly the receptor-binding domain (RBD) and N-terminal domain (NTD), emerged as the principal interface for TLR4 and MD2—a novel finding. The spike monomer exhibited stronger and more stable interactions than the trimer, supported by a greater number of hydrogen bonds and salt bridges, lower binding energies, and distinct PCA/energy landscape features. Two N-linked glycosylation sites in the monomer were positioned proximal to the MD2 binding pocket, compared to one in the trimer, suggesting a possible role in modulating receptor activation. Several hotspot residues were also identified as potential therapeutic targets. Collectively, these findings support a model in which the SARS-CoV-2 spike protein engages TLR4/MD2 through domain-specific interactions that may modulate innate immune signalling.

Background Persistent olfactory dysfunction (OD) and cognitive impairment are among the most frequently reported sequelae of long term infection with SARS-CoV-2 (long COVID-19). However, the association between these conditions remains unclear. This study investigated the correlation between OD and cognitive impairment in patients recovering from COVID-19 to identify the implications for therapeutic and rehabilitation strategies. Materials and methods A cross-sectional study of adult patients diagnosed with long COVID was conducted at a healthcare centre in Brazil. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Centre (CCCRC) test, and cognitive performance was evaluated using the Montreal Cognitive Assessment (MoCA). Statistical analyses included odds ratios (OR) and linear regression to explore the association between OD severity and cognitive scores, adjusting for potential confounders such as age, sex, and comorbidities. Results A total of 241 patients (age: 48.60 ± 12.68 years; 73% female) were included. Cognitive impairment (MoCA  23) was present in 64% of the participants. OD was identified in 92% of the patients and ranged from mild to anosmia. Linear regression analysis showed a weak yet statistically significant correlation between the CCCRC and MoCA scores (R = 0.14, p = 0.02). An OR of 2.87 (95% CI: 1.57–5.25, p = 0.00) indicated higher odds of cognitive impairment in patients with severe OD. Discussion This study supports the hypothesis that there is a weak yet significant association between OD and cognitive impairment in patients with long COVID. These findings underscore the importance of early screening for olfactory dysfunction as a potential marker of cognitive monitoring and the need for intervention in this population.

Bei Menschen mit Post-Covid-Syndrom wurde festgestellt, dass die Kreatinspeicher in Gehirn und Muskelgewebe im Durchschnitt niedriger sind als bei gesunden Menschen. Dieser Befund veranlasste die Forscher, die Wirkung einer Kreatin-Supplementierung auf die Post-Covid-Symptome zu untersuchen. In einer sechsmonatigen Interventionsstudie führte die Kreatin-Supplementierung zu einer deutlichen Verringerung der allgemeinen Müdigkeit.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we …

Virus entry is thought to involve binding a unique receptor for cell attachment and cytosolic entry. For SARS-CoV-2 underlying the COVID-19 pandemic, angiotensin-converting enzyme 2 (ACE2) is widely assumed as the receptor. Using advanced light microscopy to resolve individual virions and receptors, we found instead that heparan sulfate (HS), not ACE2, mediates SARS-CoV-2 cell-surface attachment and subsequent endocytosis. ACE2 functions only downstream of HS to enable viral genome expression. Instead of binding single HS molecules that electrostatically interact with viral surface proteins weakly, SARS-CoV-2 binds clusters of ~6–137 HS molecules projecting 60–410 nm above the plasma membrane. These tall, HS-rich clusters, present at about one per 6 μm², act as docking sites for viral attachment. Blocking HS binding with the clinically used HS-binding agent pixantrone strongly inhibited the clinically relevant SARS-CoV-2 Omicron JN.1 subvariant from attaching to and infecting human airway cells. This work establishes a revised entry paradigm in which HS clusters mediate SARS-CoV-2 attachment and endocytosis, with ACE2 acting downstream, thereby identifying HS interactions as a key anti-COVID-19 strategy. This paradigm and its therapeutic implications may apply broadly beyond COVID-19 because, analogous to SARS-CoV-2, HS binds many other viruses but is only considered an attachment regulator. ### Competing Interest Statement All authors except Jessica Matthias and Christian A. Wurm declare no competing interests. Jessica Matthias and Christian A. Wurm work for Abberior Instruments America LLC, Bethesda, MD, United States, which commercializes the MINFLUX microscope.

This randomized clinical trial evaluates the efficacy of azelastine as a preexposure prophylaxis against SARS-CoV-2 and other respiratory pathogens.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome or “Long COVID” represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of PASC, but the extent of PASC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed PASC. Compared to convalescent, PASC participants with a broad range of PASC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the PASC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis, we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in PASC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in PASC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity. ### Competing Interest Statement Jerry A. Krishnan, MD, PhD, reports grants from National Institutes of Health during the conduct of the study; research grants from the American Lung Association, BioVie Pharma, COPD Foundation, and Patient Centered Outcomes Research Institute outside the submitted work; and personal fees from AstraZeneca, Inogen, MedImmune, RespirAI, and Verona Pharma. National Institutes of Health, https://ror.org/01cwqze88, OT2HL161847

Memory T cells drive early reactogenic responses to mRNA boosters via MAIT/innate-like T cells, which are tempered by dosing interval.

Der Rechner zeigt Gefahrenlagen auf und unterstützt dabei, deren tatsächliches Risiko einzuschätzen.

After 150,000 articles and 17 million genome sequences, what has science taught us about SARS-CoV-2?

Emerging evidence suggests that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have long-term deleterious effects on the central nervous system and even contribute to post-COVID neurological syndromes. Interestingly, inflammation-induced proteolytic processing of the Spike protein of SARS-CoV-2 leads to the generation of peptides capable of aggregating into amyloid fibrils in vitro. Herein, we investigate the in vitro effect of a fibrillogenic fragment of the Spike protein [Spike 194–203 (S194)] on the aggregation and toxicity of the Parkinson’s disease (PD) protein α-synuclein (αSyn). Our results indicate that S194 fibrils stimulate in a concentration-dependent manner the fibrillation of αSyn monomer, resulting in aggregates with increased capacity of inducing lipid vesicle leakage and toxicity to neuroblastoma cells, in comparison with either αSyn or S194 alone. Bidimensional NMR (1H–15N-HSQC) suggests that S194 fibrils cause a higher perturbation in both the N-terminal region (sequence: 19–68) and the hydrophobic central domain of the αSyn monomer (sequence: 71–95), which is corroborated by protein–peptide docking and molecular dynamics simulations. In contrast with fibrils from wild-type αSyn, aggregates from the PD variant A30P exhibited a remarkable accelerative effect on S194 fibrillation. Similarly, fibrils from amyloid-β peptides, which are linked to Alzheimer’s disease, exhibited a pro-aggregating effect on the S194 monomer. Taken together, these findings might contribute to a broader understanding of the potential connections between SARS-CoV-2 infection and amyloid-related neurodegenerative disorders, highlighting areas that may warrant further investigation.

Anfang 2022 – nach Aufhebung der COVID-19- bedingten Lockdown-Maßnahmen – traten insbesondere in Großbritannien gehäuft Fälle von akuter Hepatitis unklarer Genese (acute hepatitis of unknown origin, AHUO) bei Kindern auf.

In both Sweden and Norway, the number of children seeking medical care for memory problems has increased dramatically.

Mit dem Alter werden Blutgefäße steifer und erhöhen das Risiko für Herz-Kreislauf-Erkrankungen. Was Forschende in einer neuen Studie herausgefunden haben.

This chapter extends thinking about how stigmas emerge and change over time, arguing that a dynamic network theory best reflects the complex, local, and global processes of stigma change. At the core of ‘stigma mutation’ are three dimensions of stigma (Farrimond, 2021): lineage (how stigma emerges in relation to histories and other stigma); variation (how stigma changes in relation to culture or location); and strength (how stigma intensifies and/or weakens over time). The chapter argues that these dimensions are interrelated dynamically, allowing for multiple connections which are predictable (territorialised) and unpredictable (de-territorialised). This theory enables an understanding of why stigmas cluster around already marginalised groups, but also of how unexpected connections or events can disrupt stigma. This theory is illustrated using the example of long COVID stigma, which has emerged out of COVID-19 stigma, but has its specific lineage, variations, and strengths at this cultural moment.

The biological mechanisms underlying long COVID in the pediatric population are poorly understood. Our study aimed to characterize the immune pathophysiology of long COVID in children and young people (CYP). We analyzed major immune cell compartments in PBMCs, as well as specific SARS-CoV-2 antibody response in CYP with (n=99) and without (n=18) long COVID at three months following acute infection. Our findings indicate that pediatric long COVID is associated with a dysregulated immune response characterized by altered innate immunity and overactivated T-, B- and NK-cell responses. Furthermore, CYP with long COVID had an impaired humoral response to SARS-CoV-2 marked by a dysregulated B-cell compartment and lower levels of anti-RBD IgG and IgA. This correlated with reduced neutralizing capacity against SARS-CoV-2. Random forest analysis identified CCR6 expression on myeloid cells as the most relevant biomarker that distinguishes long COVID from control individuals with 79% accuracy. ### Competing Interest Statement The authors have declared no competing interest. Barcelona City Council and the Spanish Ministry of Science and Innovation, 22S09391-001 University Hospital Germans Trias i Pujol, LC2313 Catalan Agency of Management of University and Research Grants, 2023 FI-1 00207, 2020 BP 00046 Gilead Sciences (Spain), https://ror.org/02qacef07, EU Gilead Research Scholars Program in HIV award 2021, GLD21-00070 Spanish Ministry of Science and Innovation, FJC2021-047205-I, RYC2020-028934-I/AEI/10.13039/501100011033, PID2022-139271OB-I00, CB21/13/00063 Horizon Europe Research and Innovation program, 101057100 Fundació La Marató de TV3, 202130-30-31-32

Public health is under attack. The CDC shooting underscores how misinformation fuels mistrust and danger. In this climate, evidence-based protections like masking aren’t optional—they’re essential. Layered strategies remain our best defense against deadly pathogens.

Author summary Bats carry many different viruses, some of which can infect humans. Among these, bat coronaviruses are of particular concern. To be better prepared for future pandemics, it is important to understand how many of these viruses exist and their ability to infect different hosts. However, research in this area has often focused on certain parts of the world, while other regions remain underexplored. Spain has a rich diversity of bats, but very few studies have looked for coronaviruses in bats from the Iberian Peninsula. Here, we used viral metagenomics to test for the presence of coronaviruses in more than 200 bat samples collected across Spain. We identified eight coronavirus genomes, three of which may constitute new species. We also examined how closely related they are to previously known viruses, and whether they can use the same cellular receptors as known coronaviruses. Notably, we found that one of the viruses could use human ACE2, the SARS-CoV-2 receptor. Our findings reveal that bats in Spain host a diverse range of coronaviruses, including some that could potentially infect humans. This highlights the importance of studying coronavirus diversity more broadly worldwide.

The molecular basis for differences in immune response to SARS-CoV-2 in children and adults is still unclear. Here, the authors show that antibodies are of high binding and functional quality in children with mild or asymptomatic infection, but antibody response is delayed as compared to adults.

Background Persistent symptoms and complications reported by many patients for more than four weeks after contracting coronavirus disease 2019 (COVID-19) are referred to as post-COVID-19 syndrome. These persistent symptoms can occur in individuals with both mild and severe COVID-19, though the underlying pathophysiological mechanisms remain poorly understood. This study aims to explore post-COVID-19 syndrome from a biological perspective, focusing on genomic instability. Methods In this cross-sectional study, the comet assay method was employed in March 2024 to evaluate the level of DNA damage in 29 patients to examine the post-COVID-19 syndrome state at Kausar Semnan Hospital in Iran. Levels of DNA damage were assessed using the alkaline comet assay in patients hospitalized for COVID-19, four weeks after a positive RT-PCR test. Patients were categorized based on pneumonia severity: mild (11 patients in non-ICU), moderate (10 patients in ICU and non-intubated), and severe/critical (8 patients in ICU and intubated). Ten healthy individuals who tested negative for COVID-19 were considered as a control group. Data were analyzed using descriptive and inferential statistical tests at a significance level of p  0.01 in GraphPad Prism 9 software. Results Post-COVID-19 patients exhibited significantly higher levels of DNA damage compared to healthy controls. The highest DNA damage was observed in intubated-ICU patients (mean DNA damage: 29.5%), followed by non-intubated-ICU patients (mean: 24.3%), non-ICU patients (mean: 19.1%), and healthy controls (mean: 9.4%). These findings suggest a clear correlation between COVID-19 severity and increased genomic instability. Conclusion The results of this study highlight the prevalence of DNA damage in post-COVID-19 patients, which may explain long-term genomic instability and associated health complications. The findings underscore the importance of further research into the pathophysiological mechanisms of post-COVID-19 syndrome, particularly its impact on genomic stability. This study contributes to the growing evidence that post-COVID-19 syndrome is a complex condition with virus-specific abnormalities affecting multiple biological pathways. Future studies should focus on understanding these mechanisms to develop targeted interventions for long-term COVID-19 survivors.

The COVID-19 pandemic continues to pose severe health and economic challenges, exacerbated by emerging antiviral drug resistance. As of now, there are several vaccines and a few FDA-approved drugs available; however, due to the emergence of antiviral drug resistance still there is a need for novel strategies and antiviral drugs. This study investigates honey bee-derived antimicrobial peptides (BAMPs) as potential multi-target antiviral agents against SARS-CoV-2. A total of 82 BAMPs from eight bee species, classified into seven peptide classes, were screened for favorable pharmacokinetic and pharmacodynamic properties. Finally, seventeen BAMPs were selected, modeled, and validated for further structural studies. Molecular docking revealed strong binding affinities with key viral and host targets, surpassing several FDA-approved antivirals. These interactions suggest BAMPs may inhibit viral entry, replication, and dissemination. Further, molecular dynamics simulation studies confirmed the stability, compactness, and flexibility of the docked complexes. Overall, present study highlight BAMPs as promising candidates for SARS-CoV-2 therapeutics, while warranting further in vitro and in vivo validation.

A rheumatologist calls for greater awareness among her colleagues but also emphasizes that these patients require multidisciplinary care.

A new study on acceleration of vascular aging adds to the body of evidence

SARS-CoV-2 infection can be followed by prolonged symptoms, signs and sequelae, collectively known under the term Long COVID. Hundreds of millions are estimated to suffer from Long COVID. Long COVID, therefore, is a public health crisis that deserves the utmost urgency from all relevant stakeholders, from policymakers to advocacy groups, researchers and healthcare providers. The development of effective definitions and guidelines for Long COVID is crucial to support patients and carers. In this review, I address the following two case definitions of Long COVID developed in the US as a case study for a broader discussion on the sequelae of SARS-CoV-2 infection: the U.S. Government (USG) working definition for Long COVID and the NASEM definition published in 2024. In the first part of this review, I provide a critical appraisal of the USG in light of research, pathophysiology and lived experience, building upon my intervention as a patient expert on a National Academies of Sciences, Engineering, and Medicine (NASEM) panel for defining Long COVID, which examined the USG. In the second part, I raise some pressing concerns to address when approaching Long COVID as a disease entity and as a concept, which I originally submitted to NASEM. In the third part, I offer a critical appraisal of the NASEM definition, the most recent benchmark for Long COVID in the US. The review highlights the importance of broad, expansive and inclusive definitions for Long COVID, accounting for the disease’s heterogeneous, fluctuating and multi-system manifestations. Clinical case definitions for Long COVID must retain their focus on the broader spectrum and scope of the disease entity, while incorporating feedback from people with lived experience, advocates and patient-researchers.

AbstractBackground and Aims. Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through develo