What is the duration of persistent symptoms after SARS-CoV-2 infection, and what factors are associated with their resolution?
This cross-sectional study nested in 3 French population-based cohorts found that approximately 10% of individuals with acute COVID-19 infection still had symptoms after 1 year of follow-up. The risk factors associated with the duration of these symptoms vary depending on their persistence.
This study suggests that persistent symptoms after SARS-CoV-2 infection is a public health concern.
Persistent symptoms after SARS-CoV-2 infection are an emerging public health problem. The duration of these symptoms remains poorly documented.
To describe the temporal dynamics of persistent symptoms after SARS-CoV-2 infection and the factors associated with their resolution.
Design, Setting, and Participants
This cross-sectional study involved 53 047 participants from 3 French adult population-based cohorts (CONSTANCES [Consultants des Centres d’Examens de Santé], E3N/E4N, and Nutrinet-Santé) who were included in a nationwide survey about SARS-CoV-2 infection. All participants were asked to complete self-administered questionnaires between April 1 and June 30, 2020. Variables included sociodemographic characteristics, comorbid conditions, COVID-19 diagnosis, and acute symptoms. Blood samples were obtained for serologic analysis between May 1 and November 30, 2020, from patients with SARS-CoV-2 infection defined as enzyme-linked immunosorbent assay immunoglobulin G antispike detection confirmed with a neutralization assay. A follow-up internet questionnaire was completed between June 1 and September 30, 2021, with details on persistent symptoms, their duration, and SARS-CoV-2 infection diagnosis by polymerase chain reaction.
Main Outcomes and Measures
Persistent symptoms were defined as symptoms occurring during the acute infection and lasting 2 or more months. Survival models for interval-censored data were used to estimate symptom duration from the acute episode. Multivariable adjusted hazard ratios (HRs) were estimated for age, sex, and comorbid conditions. Factors associated with the resolution of symptoms were assessed.
A total of 3972 participants (2531 women [63.7%; 95% CI, 62.2%-65.2%]; mean [SD] age, 50.9 [12.7] years) had been infected with SARS-CoV-2. Of these 3972 participants, 2647 (66.6% [95% CI, 65.1%-68.1%]) reported at least 1 symptom during the acute phase. Of these 2647 participants, 861 (32.5% [95% CI, 30.8%-34.3%]) reported at least 1 persistent symptom lasting 2 or more months after the acute phase. After 1 year of follow-up, the estimated proportion of individuals with complete symptom resolution was 89.9% (95% CI, 88.7%-90.9%) with acute symptoms. Older age (>60 years; HR, 0.78; 95% CI, 0.68-0.90), female sex (HR, 0.64; 95% CI, 0.58-0.70), history of cancer (HR, 0.61; 95% CI, 0.47-0.79), history of tobacco consumption (HR, 0.80; 95% CI, 0.73-0.88), high body mass index (≥30: HR, 0.75; 95% CI, 0.63-0.89), and high number of symptoms during the acute phase (>4; HR, 0.43; 95% CI, 0.39-0.48) were associated with a slower resolution of symptoms.
Conclusions and Relevance
In this cross-sectional study, persistent symptoms were still present in 10.1% of infected individuals at 1 year after SARS-CoV-2 infection. Given the high level of cumulative incidence of COVID-19, the absolute prevalent number of people with persistent symptoms is a public health concern.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: September 8, 2022.
Published: November 9, 2022. doi:10.1001/jamanetworkopen.2022.40985
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Robineau O et al. JAMA Network Open.
Corresponding Author: Olivier Robineau, MD, PhD, Centre Hospitalier Gustave Dron, Rue du président René Coty, 59200 Tourcoing, France (firstname.lastname@example.org).
Author Contributions: Drs Robineau and Carrat had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Robineau, Touvier, Nicol, Severi, Carrat.
Acquisition, analysis, or interpretation of data: Robineau, Zins, Touvier, Wiernik, Lemogne, de Lamballerie, Blanché, Deleuze, Saba Villarroel, Dorival, Gomes-Rima, Correia, Coeuret-Pellicer, Druesne-Pecollo, Esseddik, Ribet, Goldberg, Severi, Carrat.
Drafting of the manuscript: Robineau, Gomes-Rima, Carrat.
Critical revision of the manuscript for important intellectual content: Robineau, Zins, Touvier, Wiernik, Lemogne, de Lamballerie, Blanché, Deleuze, Saba Villarroel, Dorival, Nicol, Correia, Coeuret-Pellicer, Druesne-Pecollo, Esseddik, Ribet, Goldberg, Severi.
Statistical analysis: Robineau.
Obtained funding: Zins, Touvier, Dorival, Goldberg, Carrat.
Administrative, technical, or material support: Touvier, Blanché, Deleuze, Saba Villarroel, Dorival, Nicol, Correia, Coeuret-Pellicer, Druesne-Pecollo, Esseddik, Goldberg, Severi.
Supervision: Robineau, Nicol, Druesne-Pecollo, Esseddik, Carrat.
Conflict of Interest Disclosures: Dr Robineau reported receiving personal fees and nonfinancial support from Gilead, MSD, and ViiV outside the submitted work. Dr Lemogne reported receiving personal fees and nonfinancial support from Lundbeck and Otsuka Pharmaceutical outside the submitted work. Dr de Lamballerie reported receiving grants from the French Ministry of Research during the conduct of the study. Dr Carrat reported receiving grants from Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, and INSERM during the conduct of the study and personal fees from Sanofi outside the submitted work. No other disclosures were reported.
Funding/Support: The Santé, Pratiques, Relations et Inégalités Sociales en Population Générale Pendant la Crise COVID-19–Sérologie (SAPRIS-SERO) was supported by grants ANR-20-COVI-000 and ANR-10-COHO-06 from ANR (Agence Nationale de la Recherche), grant 20RR052-00 from Fondation pour la Recherche Médicale, and grant C20-26 from Institut National de la Santé et de la Recherche Médicale (INSERM).
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: The SAPRIS-SERO Study Group members are listed in Supplement 2.
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