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. 2022 Nov 1;5(11):e2240985.
doi: 10.1001/jamanetworkopen.2022.40985.

Long-lasting Symptoms After an Acute COVID-19 Infection and Factors Associated With Their Resolution

Olivier Robineau  1   2 , Marie Zins  3 , Mathilde Touvier  4 , Emmanuel Wiernik  3 , Cedric Lemogne  5 , Xavier de Lamballerie  6 , Hélène Blanché  7 , Jean-François Deleuze  7 , Paola Mariela Saba Villarroel  6 , Céline Dorival  1 , Jerome Nicol  1 , Roselyn Gomes-Rima  8 , Emmanuelle Correia  8 , Mireille Coeuret-Pellicer  3 , Nathalie Druesne-Pecollo  4 , Younes Esseddik  4 , Céline Ribet  3 , Marcel Goldberg  3 , Gianluca Severi  8   9 , Fabrice Carrat  1   10 ; Santé, Pratiques, Relations et Inégalités Sociales en Population Générale Pendant la Crise COVID-19–Sérologie (SAPRIS-SERO) Study Group
Collaborators, Affiliations

Long-lasting Symptoms After an Acute COVID-19 Infection and Factors Associated With Their Resolution

Olivier Robineau et al. JAMA Netw Open. .

Abstract

Importance: Persistent symptoms after SARS-CoV-2 infection are an emerging public health problem. The duration of these symptoms remains poorly documented.

Objective: 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.

Results: 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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Conflict of interest statement

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.

Figures

Figure.
Figure.. Distribution of the Number of Symptoms Depending on Time Since Acute Infection
The number of individuals reporting the number of symptoms at each time step. For example, after 52 weeks, no participant reported having more than 5 symptoms.
See this image and copyright information in PMC

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