Mechanisms of long COVID and the path toward therapeutics

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(12), P. 2112 - 2130.e10

Published: Nov. 29, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways neurodegeneration-associated changes. Similar distribution patterns SARS-CoV-2-infected mice. Injection alone was sufficient to induce neuroinflammation, proteome changes axis, anxiety-like behavior, exacerbated outcomes mouse models stroke traumatic injury. Vaccination reduced but did not eliminate Our findings suggest persistent at borders may contribute lasting sequelae COVID-19.

Language: Английский

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N-acetylcysteine (NAC) supplementation improves dyspnea and may normalize von Willebrand plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID

Gynecologic Oncology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 101682 - 101682

Published: Jan. 1, 2025

Language: Английский

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Targeting the SARS-CoV-2 reservoir in long COVID

The Lancet Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Retrospective Clinical Investigation into the Association Between Abnormal Blood Clotting, Oral Anticoagulant Therapy, and Medium-Term Mortality in a Cohort of COVID-19 Patients

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 535 - 535

Published: Feb. 20, 2025

Background/Objectives: People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. Methods: Among 1238 patients, hospitalized from 17 March 2020 15 June 2021, 247 survivors deceased within 90 days hospitalization were matched 1:1 based on age, sex, intensive care unit (ICU) admission three days. Conditional logistic regression was used estimate associations means odds ratio (OR) with 95% confidence interval (CI). Results: A univariate analysis suggested that OAT, no differently subcutaneous low-molecular-weight heparins (LMWHs) during hospitalization, has significant impact (p value > 0.05) mortality. multivariate analysis, limited baseline variables (i.e., comorbidities pharmacotherapies hospital admission) showing association < revealed that, compared patients living had cancer histories (OR 1.75, CI 1.06–2.90, p = 0.029) suffered asthma 2.25, 1.13–4.47, 0.021). In contrast, heart failure (HF), atrial fibrillation (AF), arteriopathy, chronic obstructive pulmonary disease (COPD), kidney (KF), which, found be associated endpoint 0.05), lost significance analysis. Therapy aldosterone antagonists also appeared 2.49, 1.52–4.08, 0.001); whereas, D supplementation beneficial. Although not conclusive, search into Eudravigilance database, combined consulting digital predictive platform (PLATO, polypharmacology prediction), potential off-target activities, might contribute increasing severity infection. Conclusions: retrospective clinical furnished evidences other pharmacological treatments course.

Language: Английский

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Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 98 - 98

Published: Jan. 14, 2025

Post-acute sequelae of COVID-19 (PASC) are a diverse set symptoms and syndromes driven by dysfunction multiple organ systems that can persist for years negatively impact the quality life millions individuals. We currently lack specific therapeutics patients with PASC, due in part to an incomplete understanding its pathogenesis, especially non-pulmonary sequelae. Here, we discuss three animal models have been utilized investigate PASC: non-human primates (NHPs), hamsters, mice. focus on neurological, gastrointestinal, cardiovascular PASC highlight advances mechanistic insight made using these models, as well discussing warrant continued intensive research.

Language: Английский

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Antibodies to PF4 in severe COVID-19: same but different

Blood, Journal Year: 2025, Volume and Issue: 145(6), P. 559 - 560

Published: Feb. 6, 2025

Language: Английский

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Adoptive transfer of natural killer cells in therapeutic treatment of COVID-19 patients

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 22, 2025

Abstract Background Natural killer (NK) cells are crucial constituents of innate immunity, playing a vital role in the early defense against viral infections and cancer. Their antiviral capabilities stem from direct cytotoxic activity infected immunoregulatory functions that modulate adaptive immune responses. In context Coronavirus disease (COVID-19), NK contribute to controlling replication limiting excessive inflammatory Aims This review highlights mechanisms underlying cell-mediated activity, focusing on their interactions with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). We discuss potential sources for adoptive transfer therapy, critical factors influencing therapeutic efficacy, considerations clinical translation COVID-19 treatment. Methods Various cell therapy discussed, including peripheral blood, cord genetically engineered cells. Key efficacy safety cell-based therapies analyzed, cytokine modulation, subset selection, delivery methods. Conclusion Understanding influence success can inform design more effective immunotherapies patients. Strategies improving function, such as genetic modification optimizing protocols, highlighted enhance outcomes. Graphical neutralize SARS-CoV-2 by releasing granules, inhibiting replication, modulating inflammation. They originate engineering. Therapeutic strategies include transfer, optimized delivery. Inflammation is controlled, reducing

Language: Английский

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Biological Significance of the Erythrocyte Sedimentation Rate (ESR) Test: Pandemic Reemergence of Robin Fåhraeus’s “Fibrin Coagula” – Historical Overview

Published: Feb. 24, 2025

In the pre-antibiotic era, infections were usually more frequent and serious than today. Robin Fåhraeus (1888-1958) examined erythrocyte sedimentation rate (ESR) test for infections, which was normally carried out _in vitro _with freshly drawn blood. His extensive studies on mechanism physiological significance of enhanced aggregates (rouleaux) in disease included vivo _simulation. This led him to propose an explanation finding long white strips (“fibrin coagula”) within blood vessels those who had died from infections. The surge pandemic times has likely kindled a reemergence. He further speculated both that weak aggregation red cells (RBCs) followed liberation water molecules their surfaces, importance aggregation, induced by changes serum proteins (not necessarily antibodies), extended beyond clinic. modern these have immunologically significant entropic interpretations infection-associated aggregations, whether cellular (e.g., RBC) or molecular (i.e., macromolecular polymerizations). Thus, rouleaux formation displays process at level can proceed parallel less visible level. It been proposed that, when intracellular, aggregations would discriminate between self not-self crowded cytosol. Favoured associated pyrexia, this could lead, mechanisms be determined, preferential loading peptides deemed foreign presentation as MHC complexes specific clones immune cells.

Language: Английский

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Identifying and Validating Prognostic Hyper-Inflammatory and Hypo-Inflammatory COVID-19 Clinical Phenotypes Using Machine Learning Methods

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3009 - 3024

Published: Feb. 1, 2025

COVID-19 exhibits complex pathophysiological manifestations, characterized by significant clinical and biological heterogeneity. Identifying phenotypes may enhance our understanding of the disease's diverse trajectories, benefiting practice trials. This study included adult patients with from Xinhua Hospital, affiliated Shanghai Jiao Tong University School Medicine, between December 15, 2022, February 2023. The k-prototypes clustering method was employed using 50 variables to identify phenotypes. Machine learning algorithms were then applied select key classifier for phenotype recognition. A total 1376 met inclusion criteria. K-prototypes revealed two distinct subphenotypes: Hypo-inflammatory subphenotype (824 [59.9%]) Hyper-inflammatory (552 [40.1%]). Patients in younger, predominantly female, low mortality shorter hospital stays. In contrast, older, male, exhibiting a hyperinflammatory state higher rates organ dysfunction. AdaBoost model performed best prediction (Accuracy: 0.975, Precision: 0.968, Recall: 0.976, F1: 0.972, AUROC: 0.975). "CRP", "IL-2R", "D-dimer", "ST2", "BUN", "NT-proBNP", "neutrophil percentage", "lymphocyte count" identified as top-ranked model. analysis based on symptoms comorbidities. These can be accurately recognized machine models, being optimal predicting in-hospital mortality. play role subphenotypes. Use subphenotypes risk stratification practice. closely monitored, preventive measures such early admission intensive care unit or prophylactic anticoagulation taken.

Language: Английский

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