Long COVID: current research and future directions

Infectious Diseases & Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Long coronavirus disease (COVID) is defined as the continuation or development of new symptoms three months after severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and that last for at least two months, with no other explanation their cause. This includes various clinical manifestations affect multiple organ systems, such complications in respiratory, cardiovascular, neurological, musculoskeletal systems. The most commonly reported include fatigue, cognitive dysfunction, dyspnea, chest pain; however, prevalence severity these vary greatly among individuals. underlying mechanisms long COVID are complex multifaceted, encompassing viral persistence, immune system mitochondrial abnormalities, endothelial impairment, alterations microbiome. Further, has imposed a significant burden on individuals, healthcare economy by impairing an individual’s quality life functional capacity, thereby increasing costs demand care rehabilitation services. review summarizes definition, phenotypes, mechanisms, current treatment advancements highlights specific research directions future investigation.

Language: Английский

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Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 5, 2025

Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis acute COVID-19, long-term molecular changes in COVID-19 convalescents with remain poorly understood. We prospectively recruited 70 who had been diagnosed from 7 January 2020 29 May (i.e., convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), physical examination center before pandemic, served comparison group. explored proteomic metabolomic profiles 174 plasma samples 35 CONs. comprehensive analysis investigate host up Our multi-omics revealed activation cytoskeletal organization glycolysis/gluconeogenesis, well suppression gas transport adaptive immune responses, convalescents. Additionally, metabolites involved glutathione metabolism; alanine, aspartate, glutamate ascorbate aldarate metabolism were significantly upregulated Pulmonary abnormalities persisted convalescents; impaired (DLco) was most prominent feature. used this profile develop model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) two (arachidonoyl-EA 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) identification abnormal DLco. These data provide insights concerning among discharge, clarify mechanisms driving sequelae, support development novel predict This longitudinal may illuminate trajectory altered lung function

Language: Английский

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Proteomic Analysis of 442 Clinical Plasma Samples From Individuals With Symptom Records Revealed Subtypes of Convalescent Patients Who Had COVID‐19

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(4)

Published: April 1, 2025

ABSTRACT After the coronavirus disease 2019 (COVID‐19) pandemic, postacute effects of severe acute respiratory syndrome 2 (SARS‐CoV‐2) infection have gradually attracted attention. To precisely evaluate health status convalescent patients with COVID‐19, we analyzed symptom and proteome data 442 plasma samples from healthy controls, hospitalized patients, 6 or 12 months after SARS‐CoV‐2 infection. Symptoms analysis revealed distinct relationships in patients. Results protein expression levels showed that C1QA, C1QB, C2, CFH, CFHR1, F10, which regulate complement system coagulation, remained highly expressed even at 12‐month follow‐up compared their individuals. By combining data, were categorized into three subtypes: S1 (metabolism‐healthy), S2 (COVID‐19 retention), S3 (long COVID). We speculated reporting hair loss could a better than those experiencing headaches dyspnea. Compared to other sleep disorders, appetite decrease, muscle weakness may need more attention because they classified subtype, had most COVID‐19. Subtyping COVID‐19 enable personalized treatments tailored individual needs. This study provides valuable proteomic datasets for further studies associated long COVID.

Language: Английский

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The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(795)

Published: April 23, 2025

Persistent symptoms after an acute infection is emerging public health concern, but the pathobiology of such conditions not well understood. One possible scenario involves persistence lingering antigen. We have previously reported that patients with postinfectious Lyme arthritis often harbor peptidoglycan (PG) cell wall Borrelia burgdorferi , disease agent, in synovial fluid their inflamed joints treatment. However, it yet known how B. PG persists, what form, or if may play a role other complications disease. Using murine model, we developed real-time vivo system to track as function chemistry and validated our findings using both molecular cellular approaches. Unlike typical bacterial PG, unique chemical properties polymeric drive liver accumulation, where material persists for weeks. Kupffer cells hepatocytes phagocytose retain and, although occupancy coincides minimal pathology, organ-specific secreted protein profiles produced under these bear some similarities proteins enriched chronic illness infection. Moreover, transcriptomic profiling indicated affects energy metabolism peripheral blood mononuclear cells. Our provide mechanistic insights into pathogenic molecule can persist agent clearance, potentially contributing

Language: Английский

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Identification of soluble biomarkers that associate with distinct manifestations of long COVID

Nature Immunology, Journal Year: 2025, Volume and Issue: 26(5), P. 692 - 705

Published: April 30, 2025

Language: Английский

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Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases

Proteomes, Journal Year: 2024, Volume and Issue: 12(1), P. 9 - 9

Published: March 21, 2024

Background: Very little is known about the proteome of human olfactory system and how diseases associated with dysfunctions can affect it. With this review, we try to summarize existing literature on use technique for a better understanding neurodegenerative disease process. Methods: We used PubMed database found different articles which were then selected independently by three authors. Results: 157 articles, which, after careful selection, only 30 analyzed in review. presented all associations identified between protein/pathway alterations SARS-CoV-2 infection. Conclusions: think that through blood, saliva, mucus analysis could be new way understand, diagnose, finally treat diseases.

Language: Английский

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Oxidative Stress is a shared characteristic of ME/CFS and Long COVID

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 5, 2024

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need define the molecular underpinnings these conditions. By studying bioenergetic characteristics peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, LC, we find both ME/CFS LC donors exhibit signs elevated oxidative stress, relative especially memory subset. Using combination flow cytometry, bulk RNA-seq analysis, mass spectrometry, systems chemistry also observed aberrations ROS clearance pathways including glutathione levels, decreases mitochondrial superoxide dismutase peroxidase 4 mediated lipid damage. Critically, changes redox show striking sex-specific trends. While females diagnosed with higher total calcium males diagnosis normal but larger Further analyses that levels correlates hyperproliferation T cells females, consistent known role initiation proliferation. This can be attenuated by metformin, suggesting this FDA-approved drug as possible treatment, suggested recent clinical study patients. Thus, mechanistically related could quantitative cell measurements. We suggest effective, patient tailored drugs might discovered using standard lymphocyte stimulation assays.

Language: Английский

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Can inflammatory plasma proteins predict Long COVID or Fatigue severity after SARS-CoV-2 infection?

Virus Research, Journal Year: 2024, Volume and Issue: 344, P. 199363 - 199363

Published: March 22, 2024

To investigate whether specific immune response plasma proteins can predict an elevated risk of developing Long COVID symptoms or fatigue severity after SARS-CoV-2 infection.

Language: Английский

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Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study

BMC Pediatrics, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 2, 2024

Abstract Background The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number pediatric hospitalizations and changed characteristics compared to classical H1N1 pre-COVID-19 era. This study aimed evaluate clinical severity children hospitalized with during period, construct a novel prediction model for severe infection. Methods total 757 inpatients from nine tertiary public hospitals Yunnan Shanghai, China, were retrospectively included, which 431 patients diagnosed between February 2023 July divided into group, while remaining 326 November 2018 April 2019 group. 1:1 propensity-score matching (PSM) was adopted balance demographic differences pre- groups, then across these two groups based on laboratory indicators. Additionally, subgroup analysis original group (without PSM) performed investigate independent risk factors post-COIVD-19 Specifically, Least Absolute Shrinkage Selection Operator (LASSO) regression applied select candidate predictors, logistic used further identify factors, thus establishing model. Receiver operating characteristic (ROC) curve calibration utilized assess discriminative capability accuracy model, decision (DCA) determine usefulness Results After PSM, showed longer fever duration, higher peak, more frequent cough seizures, as well levels C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) fibrinogen, mechanical ventilation rate, length hospital stay (LOS), proportion (all P < 0.05), Moreover, age, BMI, leucocyte count, lymphocyte proportion, CD3 + T cells, tumor necrosis factor α (TNF-α), IL-10 confirmed be independently associated integrating above eight variables established, this had good discrimination, accuracy, practicability. Conclusions Pediatric overall disease than period. Meanwhile, seizures prominent Clinicians should aware changes such work. Furthermore, simple practical constructed internally validated here, performance predicting Graphical

Language: Английский

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Unravelling long COVID: insights from proteomics and considerations for comprehensive understanding

EBioMedicine, Journal Year: 2024, Volume and Issue: 101, P. 105023 - 105023

Published: Feb. 19, 2024

Long COVID, characterized by persistent symptoms, lacks clear diagnostic and treatment approaches due to uncertain underlying mechanisms. Gu colleagues delve into the proteomic landscape of COVID-19 survivors over two years, offering insights recovery dynamics potential biomarkers.1Gu X. Wang S. Zhang W. et al.Probing long COVID through a lens: comprehensive two-year longitudinal cohort study hospitalised survivors.eBioMedicine. 2023; 98104851Summary Full Text PDF Scopus (4) Google Scholar However, certain aspects require consideration for more understanding. The impact vaccination on is overlooked, hindering interplay between recovery. With up 81.2% vaccinated during study,1Gu influence differentially expressed proteins remains unexplored, despite evidence supporting post-infection in reducing risk.2Ayoubkhani D. Bermingham C. Pouwels K.B. al.Trajectory covid symptoms after covid-19 vaccination: community based study.BMJ. 2022; 377e069676PubMed Data completeness concerns arise as questionnaire details, including education, alcohol consumption, personal medical history, family are mentioned but not reported.1Gu Integrating data with laboratory findings would enhance understanding factors influencing post-COVID changes. Key associated post-COVID-19 identified complement coagulation pathways, emphasizing cardiovascular risks.1Gu Existing studies underline disease's association COVID,3Wahlgren Forsberg G. Divanoglou A. al.Two-year follow-up patients condition Sweden: prospective study.Lancet Reg Health Eur. 28100595PubMed Scholar, 4Wan E.Y.F. Mathur R. al.Association short- long-term risk disease mortality: UK Biobank.Cardiovasc Res. 119: 1718-1727Crossref PubMed (35) 5Xie Y. Xu E. Bowe B. Al-Aly Z. Long-term outcomes COVID-19.Nat Med. 28: 583-590Crossref (873) critical gap lies absence cardiac function assessments re-admission related protein Additional details needed proper contextualization analysis. In principal components analysis (Figure 1B–D), projection encompassing all timepoints controls facilitate interpretation. distinct clusters observed healthy at 24 months lack meaningful discussion. machine learning model's presentation classifying stages problematic training use, especially fewer observations than features. clarity leave-one-out cross-validation issues repeated genomic profiling warrant careful conclusion, while al.'s provides valuable changes biomarkers addressing gaps influence, completeness, assessment, methodological its clinical relevance contribute thorough post-SARS-CoV-2 infection dynamics. CY SJT conceived manuscript. conducted search drafted CY, CPS revised manuscript accepted final version publication. reported grant from Canadian Institutes Research (grant number: 177747). No other conflicts were reported. Authors' reply Letter regarding "Probing Proteomic Lens: Comprehensive Two-Year Longitudinal Cohort Study Hospitalised Survivor"In letter our Survivors", reader pointed out (DEPs) COVID. To address this concern, we have analysed correlation 249 DEPs. After adjustment age, sex, smoking status, body mass index, comorbidity, severity acute phase, partial coefficients DEPs ranged −0.22 0.18. Full-Text Open Access

Language: Английский

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