Covid19-Sources

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

Eine neue Studie zeigt, dass Covid-Infektionen die Blutgefäße schneller altern lassen könnten. Besonders Frauen und Ungeimpfte sind gefährdet. Experten sprechen von einem Weckruf und fordern weitere Untersuchungen.

Background: SARS-CoV-2, originally described as a respiratory pathogen, has been identified as a multisystem disease with complex and interconnected pathophysiological processes. Methods: The PRISMA framework was used to systematically review the evidence and identify and synthesize it in PubMed, Scopus and Web of Science between January 2020 and December 2025. Of the 1,410 screened records, 147 peer-reviewed studies involving more than 2 million patients were included. The frequency of organ involvement, important biomarkers and long-term outcomes were derived and the quality of the studies was assessed using standardized tools. Results: The quantitative synthesis showed that 78 % of hospitalized patients had pulmonary involvement, 32 % cardiovascular, 43 % neurological and 28 % renal, with 10–35 % showing persistent organ dysfunction at 6 months post-infection. The most common were cytokine storm (IL-6 100 pg/mL in 72% of severe cases), endothelial dysfunction (biomarkers elevated in 87% of patients) and microvascular thrombosis (D-dimer 2000 ng/mL in 46% of patients). Most domains were scored as having moderate-to-high confidence in quality assessment. Conclusions: COVID-19 has long-term, multi-organ sequelae that require integrated multidisciplinary management. Healthcare systems should be ready to participate in long-term monitoring, rehabilitation and special therapeutic development. The results offer a strong evidence base for clinical practice and post-pandemic health policy.

Background COVID-19 reinfections have emerged as a critical concern, particularly in relation to post-acute sequelae of SARS-CoV-2 infection, commonly known as long COVID. Long COVID is known to manifest diverse, debilitating symptoms across all demographics. Limited studies have investigated the causal relationship of COVID-19 reinfections and long COVID. Methods We leveraged demographically diverse electronic health records from the COVID-19 enclave of the National Clinical Cohort Collaborative, part of the RECOVER initiative, to create a matched cohort of reinfected and control adults. All participants had at least one documented COVID-19 infection. We used one-to-one coarsened exact matching on sex, race/ethnicity, age, healthcare utilization, existing comorbidities, site of care, and the timing and severity of first infection. Index dates were assigned to each matched pair as the date of reinfection for the reinfected case. Long COVID was defined using a machine learning computable phenotype trained on clinically diagnosed long COVID cases. Cumulative incidence one year after index was calculated using an Aalen-Johansen estimator. Risk ratios were calculated by taking the ratio of long COVID incidence among reinfected and control cases. Results We found that reinfection resulted in a significantly higher risk of long COVID compared to not being reinfected (risk ratio, 1.35, 95% CI, 1.32-1.39; risk difference, 0.029, 95% CI, 0.027-0.031). This effect was consistent across most stratifications. Conclusions We found that COVID-19 reinfection resulted in a roughly 35% increase in the incidence of long COVID in a matched cohort using observational electronic health records. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by NCATS Contract No. 75N95023D00001, Axle Informatics Subcontract: NCATS-P00438-B, and by the RECOVER Initiative (OT2HL161847-01). ### 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 Johns Hopkins University gave ethical approval for data transfer for N3C IRB of RTI International waived ethical approval for analysis for this study. 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 used and produced in the present work are available online to registered users of the National Clinical Cohort Collaborative (N3C). More information on how to register and obtain access can be found at https://covid.cd2h.org/for-researchers

Epidemiological estimates from wastewater are not biased by testing rates but may be subject to other biases. Here, the authors investigate the impact of variable virus shedding profiles for different SARS-CoV-2 variants on estimates of their selection advantage.

Background and Objectives: COVID-19 may have long-term adverse effects on bone health, particularly in individuals aged ≥50 years with obesity or diabetes, who are predisposed to impaired bone quality. Materials and Methods: This retrospective cohort study used TriNetX data from 141 healthcare organizations across North America and Western Europe. Patients aged ≥50 years with overweight (body mass index 25–30 kg/m2), obesity (body mass index ≥ 30 kg/m2), or type 2 diabetes (T2DM) and COVID-19 (2019–2024) were propensity score-matched to non-COVID-19 controls. Exclusion criteria included prior overweight, obesity, diabetes, osteoporosis, T-score ≤ −2.5, Z score ≤ −2.0, fractures, pneumonia, tuberculosis, and cancer. Outcomes included new-onset osteoporosis, fragility fractures, and low T-scores (≤−2.5). Cox regression estimated hazard ratios (HRs); sensitivity analyses assessed lag effects (1–4 years). Results: Among 327,933 matched pairs, COVID-19 was linked to increased osteoporosis risk at 3 years (HR, 1.039; 95% CI, 1.003–1.077) and 6 years (HR, 1.095; 95% CI, 1.059–1.133). Sensitivity analysis showed rising risk with longer lag times: HRs were 1.212, 1.379, 1.563, and 1.884 at 1 to 4 years, respectively. Subgroup analyses confirmed consistent trends. Conclusions: COVID-19 is independently associated with elevated long-term osteoporosis risk in older adults with new-onset overweight, obesity, or T2DM, peaking at 4 years post-infection and persisting through 6 years.

SARS-CoV-2 infections in children lead to symptoms from mild respiratory illness to severe postacute sequelae of COVID-19, including multisystem inflammatory syndrome in Children (MIS-C). We conducted a metabolic profiling of 147 children’s serum samples, including acute COVID-19 patients, MIS-C patients, and healthy controls. Using nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry, we measured 1101 metabolites. The results revealed distinct metabolic profiles in acute COVID-19 and MIS-C patients, with significant alterations in lipid classes. Both conditions exhibited an elevated Apo-B100/Apo-A1 ratio and increased serum inflammatory markers. MIS-C patients showed unique disruptions, including increased triglycerides and altered lipoprotein composition. Despite milder clinical respiratory symptoms, children’s metabolic disturbances mirrored those seen in severe adult COVID-19 patients, indicating a shared inflammatory response to SARS-CoV-2. This suggests potential long-term health impacts, underscoring the need for continued research into the metabolic consequences of COVID-19 in children.

Background: Coronavirus Disease 2019 has been associated with dysfunction in multiple endocrine organs, including the thyroid gland. While evidence suggests SARS-CoV-2 may influence thyroid function and promote oncogenesis through inflammation and cytokine storms, its role in thyroid cancer remains unclear. This study investigates whether COVID-19 is associated with an increased risk of thyroid cancer development. Methods: We conducted a retrospective cohort study using the TriNetX global federated health research database, encompassing data from 151 healthcare organizations. Adult patients with confirmed COVID-19 between 1 December 2019 and 31 December 2023, were included and compared to a matched cohort without COVID-19. Patients with prior thyroid cancer history or who had received COVID-19 vaccination were excluded in both groups. Propensity score matching (1:1) was performed for age, gender, and overweight/obesity status. The primary outcome was that new-onset thyroid cancer was diagnosed at least one year after COVID-19 diagnosis. Hazard ratios were calculated using Cox proportional hazards models, and subgroup analyses were performed based on age, gender, thyroid function status and treatment modalities. Results: After matching, a significantly higher thyroid cancer incidence was observed between the post-COVID and non-COVID groups. Subgroup analysis revealed a significantly higher risk of thyroid cancer development following COVID-19 diagnosis in patients who developed hyperthyroidism (HR 2.14, 95% CI: 1.04–4.46) or hypothyroid-ism (HR 1.83, 95% CI: 1.12–2.97) compared with the non-COVID population. Male patients also exhibited a higher risk of thyroid cancer after COVID-19 (HR 1.22, 95% CI 1.02–1.46). For patients with hyperthyroidism or hypothyroidism, those who had prior COVID-19 exhibited a relatively higher risk of developing thyroid cancer than those without a history of COVID-19 (HR 4.387, 95% CI: 2.08–9.24 for hyperthyroidism; HR 2.58, 95% CI: 1.58–4.22 for hypothyroidism). Conclusions: Patients with COVID-19 exhibited an increase in thyroid cancer risk, with specific subgroups—male adults and those with post-infectious thyroid dysfunction—also exhibiting increased risk. These findings suggest a potential relationship between SARS-CoV-2 and thyroid oncogenesis, warranting further prospective research.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long Covid-19 (LC-19) are complex conditions with no diagnostic markers or consensus on disease progression. Despite extensive research, no in vitro model exists to study skeletal muscle wasting, peripheral weakness, or potential therapies. We developed 3D in vitro skeletal muscle tissues to map muscle adaptations to patient sera over time. Short exposures (48 H) to patient sera led to a significant reduction in muscle contractile strength. Transcriptomic analysis revealed the upregulation of protein translation, glycolytic enzymes, disturbances in calcium homeostasis, hypertrophy, and mitochondrial hyperfusion. Structural analyses confirmed myotube hypertrophy and elevated mitochondrial oxygen consumption In ME/CFS. While muscles initially adapted by increasing glycolysis, prolonged exposure (96–144 H) caused muscle fragility and weakness, with mitochondria fragmenting into a toroidal conformation. We propose that skeletal muscle tissue in ME/CFS and LC-19 progresses through a hypermetabolic state, leading to severe muscular and mitochondrial deterioration. This is the first study to suggest such transient metabolic adaptation.