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Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study

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Abstract

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89–2.32) to 3.01 (2.68–3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01–4.14) and 3.03 (2.69–3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

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Fig. 1: Association of depressive or anxiety symptoms before or at the beginning of the pandemic with the incidence of at least one persistent symptom 7 to 10 months later among participants with or without SARS-CoV-2 infection.

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Acknowledgements

The CONSTANCES cohort benefits from grant ANR-11-INBS-0002 from the French National Research Agency. CONSTANCES is supported by the Caisse Nationale d’Assurance Maladie, the French Ministry of Health, the Ministry of Research, and the Institut National de la Santé et de la Recherche Médicale (INSERM). CONSTANCES is also partly funded by AstraZeneca, Lundbeck, L’Oréal, and Merck Sharp & Dohme Corp. The Santé, Pratiques, Relations et Inégalités Socials en Population Générale Pendant la Crise COVID-19 (SAPRIS) and SAPRIS-Sérologie (SERO) study was supported by grants ANR-10-COHO-06 and ANR-20-COVI-000 from the Agence Nationale de la Recherche; grant 20DMIA014–0 from Santé Publique France; grant 20RR052–00 from the Fondation pour la Recherche Médicale; and grant C20–26 from INSERM. The present study was supported by a grant “AAP Covid long 2022-1” from the Agence nationale de recherches sur le sida et les hépatites virales (ANRS) | Maladies infectieuses émergentes. Dr Gouraud and Dr Lemogne were supported by a grant from “la Fondation de l’Assistance Publique - Hôpitaux de Paris”.

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Authors and Affiliations

  1. Université Paris Cité, « Population-based Cohorts Unit », INSERM, Paris Saclay University, UVSQ, UMS 011, Paris, France

    Joane Matta, Emmanuel Wiernik, Baptiste Pignon, Sofiane Kab, Marcel Goldberg & Marie Zins

  2. Sorbonne Université, Inserm, Institut Pierre-Louis d’Epidémiologie et de Santé Publique, Paris, France

    Olivier Robineau & Fabrice Carrat

  3. EA2694, Univ Lille, Centre Hospitalier de, Tourcoing, France

    Olivier Robineau

  4. Département de santé publique, AP-HP, Hôpital Saint-Antoine, Paris, France

    Fabrice Carrat

  5. Université Paris-Saclay, UVSQ, INSERM, CESP U1018, Gustave Roussy, Villejuif, France

    Gianluca Severi

  6. Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy

    Gianluca Severi

  7. Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Centre of Research in Epidemiology and StatisticS (CRESS) – Université Paris Cité, Bobigny, France

    Mathilde Touvier

  8. Service de Psychiatrie de l’adulte, AP-HP, Hôpital Hôtel-Dieu, Paris, France

    Clément Gouraud, Charles Ouazana Vedrines & Cédric Lemogne

  9. Université Paris Cité, and Université Sorbonne Paris Nord, Inserm, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS), Paris, France

    Clément Gouraud, Charles Ouazana Vedrines & Cédric Lemogne

  10. Université Paris Cité, VIFASOM (Vigilance Fatigue Sommeil et Santé Publique), Paris, France

    Victor Pitron

  11. Centre du Sommeil et de la Vigilance-Pathologie professionnelle, APHP, Hôtel-Dieu, Paris, France

    Victor Pitron

  12. Université de Paris, Service de Médecine interne, AP-HP, Hôpital européen Georges-Pompidou, Paris, France

    Brigitte Ranque

  13. Université Paris Cité, INSERM U1266, Institut de Psychiatrie et Neuroscience de Paris, Paris, France

    Nicolas Hoertel

  14. Service de Psychiatrie et Addictologie de l’adulte et du sujet âgé, AP-HP, Hôpital Corentin-Celton, Issy-les-Moulineaux, France

    Nicolas Hoertel

Authors
  1. Joane Matta
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  2. Olivier Robineau
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  14. Marcel Goldberg
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  16. Cédric Lemogne
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Contributions

JM and CL take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. CL designed the study; MG, MT, GS, and MZ acquired the data; JM and CL performed statistical analysis. All authors contributed to the interpretation of data. JM and CL drafted the article; OR, EW, FC, GS, MT, CG, COV, VP, BR, BP, NH, SK, MG, MZ revised it critically for important intellectual content. All authors have read and approved the final manuscript. All authors confirm that they had full access to all the data in the study and accept responsibility to submit for publication.

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Correspondence to Cédric Lemogne.

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Competing interests

Dr Robineau reported personal fees and nonfinancial support from Gilead, ViiV Healthcare, and Merck Sharp & Dohme Corp outside the submitted work. Dr Pitron reported personal fees from Grunenthal, outside the submitted work. Dr Lemogne reported non-financial support from Nordic Pharma, outside the submitted work. No other disclosures were reported.

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Matta, J., Robineau, O., Wiernik, E. et al. Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study. Mol Psychiatry 28, 4261–4271 (2023). https://doi.org/10.1038/s41380-023-02179-9

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