Long-lasting Symptoms After an Acute COVID-19 Infection and Factors Associated With Their Resolution
Authors: Robineau Olivier , Zins Marie , Touvier Mathilde , Wiernik Emmanuel , Lemogne Cedric , de Lamballerie Xavier , Blanché Hélène , Deleuze Jean-François , Saba Villarroel Paola Mariela , Dorival Céline , Nicol Jerome , Gomes-Rima Roselyn , Correia Emmanuelle , Coeuret-Pellicer Mireille , Druesne-Pecollo Nathalie , Esseddik Younes , Ribet Céline , Goldberg Marcel , Severi Gianluca , Carrat Fabrice ,   Santé, Pratiques, Relations et Inégalités Sociales en Population Générale Pendant la Crise COVID-19–Sérologie (SAPRIS-SERO) Study Group, Carrat Fabrice , Zins Marie , Severi Gianluca , Touvier Mathilde , Blanché Hélène , Deleuze Jean-François , De Lambalerie Xavier , Lusivika-Nzinga Clovis , Pannetier Gregory , Lapidus Nathanael , Goderel Isabelle , Dorival Céline , Nicol Jerome , Robineau Olviier , Kab Sofiane , Renuy Adeline , Le-Got Stéphane , Ribet Céline , Pellicer Miereille , Wiernik Emmanuel , Goldberg Marcel , Artaud Fanny , Gerbouin-Rérolle Pascale , nguix Mélodie , Laplanche Camille , Gomes-Rima Roselyn , Hoang Lyan , Correia Emmanuelle , Barry Alpha Amadou , Senina Nadège , Allegre Julien , Szabo de Edelenyi Fabien , Druesne-Pecollo Nathalie , Esseddik Yunes , Hercberg Serge , Deschasaux Mélanie , Sébaoun Jean-Marc , Baudouin Jean-Christophe , Gressin Laetitia , Morel Valérie , Ouili Ouissam , Ninove Laetitia , Priet Stéphane , Saba Villarroel Paola Mariela , Fourié Toscane , Ali Souand Mohamed , Amroun Abdenour , Seston Morgan , Ayhan Nazli , Pastorino Boris 
Published: November 2022

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 (&amp;gt;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 (&amp;gt;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.