Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context

Summary: Background: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammat...

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Main Authors: Olivier Robineau, Sophie Hüe, Mathieu Surenaud, Cédric Lemogne, Céline Dorival, Emmanuel Wiernik, Sebastien Brami, Jerome Nicol, Xavier de Lamballerie, Hélène Blanché, Jean-François Deleuze, Céline Ribet, Marcel Goldberg, Gianluca Severi, Mathilde Touvier, Marie Zins, Yves Levy, Jean-Daniel Lelievre, Fabrice Carrat
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396425002361
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author Olivier Robineau
Sophie Hüe
Mathieu Surenaud
Cédric Lemogne
Céline Dorival
Emmanuel Wiernik
Sebastien Brami
Jerome Nicol
Xavier de Lamballerie
Hélène Blanché
Jean-François Deleuze
Céline Ribet
Marcel Goldberg
Gianluca Severi
Mathilde Touvier
Marie Zins
Yves Levy
Jean-Daniel Lelievre
Fabrice Carrat
author_facet Olivier Robineau
Sophie Hüe
Mathieu Surenaud
Cédric Lemogne
Céline Dorival
Emmanuel Wiernik
Sebastien Brami
Jerome Nicol
Xavier de Lamballerie
Hélène Blanché
Jean-François Deleuze
Céline Ribet
Marcel Goldberg
Gianluca Severi
Mathilde Touvier
Marie Zins
Yves Levy
Jean-Daniel Lelievre
Fabrice Carrat
author_sort Olivier Robineau
collection DOAJ
description Summary: Background: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammatory abnormalities is inconsistent in the literature. The hypothesis that different pathophysiological mechanisms could explain the persistent symptoms needs to be explored. Methods: The COPER cohort is a prospective study that included participants with PASC and with a history of COVID-19 without persistent symptoms. None were hospitalised for COVID-19. Participants underwent two home visits six months apart for biological sample collection and completed questionnaires on medical history, infection, vaccination, symptoms, and mental health. The study analysed association between persistent symptoms and 14 blood biomarkers, comparing participants with PASC with recovered participants. Findings: Between June and November 2022, 1000 participants were included in the study, 199 were excluded due to missing data or sample (35), SARS-CoV-2 infection less than 3 months (36) or lack of known SARS-CoV-2 infection and negative serology (128), with two groups analysed: recovered (n = 490), PASC (n = 311). Participants with PASC were more frequently women, had a higher BMI and a median number of 3 persistent symptoms, with common symptoms being asthenia, dyspnoea, cough, and sleep disorders. Biological analysis revealed significant associations between certain PACS symptoms and biomarkers of viral activation (IFNγ, IP-10), COVID-19 severity (CD163) and vascular activation (VCAM-1, ICAM-1), mainly in subjects whose symptoms had lasted less than a year. However, these associations did not persist over time. Interpretation: The results suggest a polymorphic and dynamic pathophysiology according to symptoms and time since infection. Other hypotheses, beyond those related to persistent inflammation, should be explored. Funding: French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation.
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spelling doaj-art-baff68e23fa040aaad57fc790d05648d2025-08-20T02:17:13ZengElsevierEBioMedicine2352-39642025-07-0111710579210.1016/j.ebiom.2025.105792Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in contextOlivier Robineau0Sophie Hüe1Mathieu Surenaud2Cédric Lemogne3Céline Dorival4Emmanuel Wiernik5Sebastien Brami6Jerome Nicol7Xavier de Lamballerie8Hélène Blanché9Jean-François Deleuze10Céline Ribet11Marcel Goldberg12Gianluca Severi13Mathilde Touvier14Marie Zins15Yves Levy16Jean-Daniel Lelievre17Fabrice Carrat18Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, France; EA2694, Centre Hospitalier de Tourcoing, Univ Lille, France; Corresponding author. Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier Gustave Dron, Tourcoing 59208, France.Faculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, FranceFaculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, FranceCenter for Research in Epidemiology and StatisticS (CRESS), Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Paris, France; Service de Psychiatrie de l’adulte, AP-HP, Hôpital Hôtel-Dieu, Paris, FranceSorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, FrancePopulation-based Epidemiological Cohorts, UMS 11, Université de Paris Cité, Université de Paris Saclay, Université de Versailles St Quentin, Inserm, Villejuif, FranceFaculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, FranceSorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, FranceUnité des Virus Emergents, UVE: Aix Marseille University, IRD 190, Inserm 1207, IHU Méditerranée Infection, Marseille, FranceFondation Jean Dausset-CEPH (Centre d’Etude du Polymorphisme Humain), Paris, FranceFondation Jean Dausset-CEPH (Centre d’Etude du Polymorphisme Humain), Paris, FrancePopulation-based Epidemiological Cohorts, UMS 11, Université de Paris Cité, Université de Paris Saclay, Université de Versailles St Quentin, Inserm, Villejuif, FrancePopulation-based Epidemiological Cohorts, UMS 11, Université de Paris Cité, Université de Paris Saclay, Université de Versailles St Quentin, Inserm, Villejuif, FranceCESP UMR1018, Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, ItalySorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center – University of Paris (CRESS), Bobigny, FrancePopulation-based Epidemiological Cohorts, UMS 11, Université de Paris Cité, Université de Paris Saclay, Université de Versailles St Quentin, Inserm, Villejuif, FranceFaculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, France; Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service de maladies Infectieuses et Immunologie Clinique, Créteil, FranceFaculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, France; Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service de maladies Infectieuses et Immunologie Clinique, Créteil, FranceSorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, France; Département de Santé Publique, Hôpital Saint-Antoine, APHP, Paris, FranceSummary: Background: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammatory abnormalities is inconsistent in the literature. The hypothesis that different pathophysiological mechanisms could explain the persistent symptoms needs to be explored. Methods: The COPER cohort is a prospective study that included participants with PASC and with a history of COVID-19 without persistent symptoms. None were hospitalised for COVID-19. Participants underwent two home visits six months apart for biological sample collection and completed questionnaires on medical history, infection, vaccination, symptoms, and mental health. The study analysed association between persistent symptoms and 14 blood biomarkers, comparing participants with PASC with recovered participants. Findings: Between June and November 2022, 1000 participants were included in the study, 199 were excluded due to missing data or sample (35), SARS-CoV-2 infection less than 3 months (36) or lack of known SARS-CoV-2 infection and negative serology (128), with two groups analysed: recovered (n = 490), PASC (n = 311). Participants with PASC were more frequently women, had a higher BMI and a median number of 3 persistent symptoms, with common symptoms being asthenia, dyspnoea, cough, and sleep disorders. Biological analysis revealed significant associations between certain PACS symptoms and biomarkers of viral activation (IFNγ, IP-10), COVID-19 severity (CD163) and vascular activation (VCAM-1, ICAM-1), mainly in subjects whose symptoms had lasted less than a year. However, these associations did not persist over time. Interpretation: The results suggest a polymorphic and dynamic pathophysiology according to symptoms and time since infection. Other hypotheses, beyond those related to persistent inflammation, should be explored. Funding: French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation.http://www.sciencedirect.com/science/article/pii/S2352396425002361SARS-CoV-2PASCLong COVIDBiomarkersPost-infectious symptomsPostacute symptoms following COVID-19
spellingShingle Olivier Robineau
Sophie Hüe
Mathieu Surenaud
Cédric Lemogne
Céline Dorival
Emmanuel Wiernik
Sebastien Brami
Jerome Nicol
Xavier de Lamballerie
Hélène Blanché
Jean-François Deleuze
Céline Ribet
Marcel Goldberg
Gianluca Severi
Mathilde Touvier
Marie Zins
Yves Levy
Jean-Daniel Lelievre
Fabrice Carrat
Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
EBioMedicine
SARS-CoV-2
PASC
Long COVID
Biomarkers
Post-infectious symptoms
Postacute symptoms following COVID-19
title Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
title_full Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
title_fullStr Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
title_full_unstemmed Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
title_short Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort studyResearch in context
title_sort symptoms and pathophysiology of post acute sequelae following covid 19 pasc a cohort studyresearch in context
topic SARS-CoV-2
PASC
Long COVID
Biomarkers
Post-infectious symptoms
Postacute symptoms following COVID-19
url http://www.sciencedirect.com/science/article/pii/S2352396425002361
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