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Multicenter Study
. 2025 Mar 7;23(1):144.
doi: 10.1186/s12916-025-03952-z.

Psychiatric and neuropsychiatric sequelae of COVID-19 within 2 years: a multinational cohort study

Yi Chai #  1   2   3 , Ivan C H Lam #  2 , Kenneth K C Man  2   4   5 , Joseph F Hayes  6   7 , Eric Y F Wan  2   5   8 , Xue Li  2   5   9 , Celine S L Chui  5   10   11 , Wallis C Y Lau  2   4   5 , Xiaoyu Lin  12 , Can Yin  12 , Min Fan  2 , Esther W Chan  2   5   13 , Ian C K Wong  2   14 , Hao Luo  15
Affiliations
Multicenter Study

Psychiatric and neuropsychiatric sequelae of COVID-19 within 2 years: a multinational cohort study

Yi Chai et al. BMC Med. .

Abstract

Background: The long-term psychiatric and neuropsychiatric sequelae of COVID-19 across diverse populations remain not fully understood. This cohort study aims to investigate the short-, medium-, and long-term risks of psychiatric and neuropsychiatric disorders following COVID-19 infection in five countries.

Methods: This population-based multinational network study used electronic medical records from France, Italy, Germany, and the UK and claims data from the USA. The initial target and comparator cohorts were identified using an exact matching approach based on age and sex. Individuals diagnosed with COVID-19 or those with a positive SARS-CoV-2 screening test between December 1, 2019, and December 1, 2020, were included as targets. Up to ten comparators without COVID-19 for each target were selected using the propensity score matching approach. All individuals were followed from the index date until the end of continuous enrolment or the last healthcare encounter. Cox proportional hazard regression models were fitted to estimate the risk of incident diagnosis of depression, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, psychoses, personality disorders, self-harm and suicide, sleep disorders, dementia, and neurodevelopmental disorders within the first 6 months (short-term), 6 months to 1 year (medium-term), and 1 to 2 years (long-term) post-infection.

Results: A total of 303,251 individuals with COVID-19 and 22,108,925 individuals without COVID-19 from five countries were originally included. Within the first 6 months, individuals with COVID-19 had a significantly higher risk of any studied disorders in all databases, with Hazard Ratios (HRs) ranging from 1.14 (95% CI, 1.07-1.22) in Germany to 1.89 (1.64-2.17) in Italy. Increased risks were consistently observed for depression, anxiety disorders, and sleep disorders across almost all countries. During the medium- and long-term periods, higher risks were observed only for depression (medium-term: 1.29, 1.18-1.41; long-term: 1.36, 1.25-1.47), anxiety disorders (medium-term: 1.29, 1.20-1.38; long-term: 1.37, 1.29-1.47), and sleep disorders (medium-term: 1.10, 1.01-1.21; long-term: 1.14, 1.05-1.24) in France, and dementia (medium-term: 1.65, 1.28-2.10) in the UK.

Conclusions: Our study suggests that increased risks of psychiatric and neuropsychiatric outcomes were consistently observed only within, and not after, the 6-month observation period across all databases, except for certain conditions in specific countries.

Keywords: Long COVID; Mental health; Neuropsychiatric disorders; OMOP CDM; Psychiatric disorders; SARS-CoV-2.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The data partners have obtained institutional review board exemption for their participation in this study. Informed consent was waived because the study used deidentified data, and no patients were contacted. Consent for publication: Not applicable. Competing interests: Kenneth K.C. Man reports grants from the CW Maplethorpe Fellowship, National Institute of Health Research, UK, Hong Kong Research Grant Council and the European Commission Horizon 2020 Framework, personal fees from IQVIA and grants from Amgen and GlaxoSmithKline, outside the submitted work; Joseph F. Hayes reports grants from UKRI, NIHR UCLH Biomedical Research Centre, and Wellcome Trust and Consultancy Fees from Wellcome Trust and juli Health, outside the submitted work; Xue Li reports grants from the Hong Kong Health and Medical Research Fund (HMRF, HMRF Fellowship Scheme, HKSAR), Research Grants Council Early Career Scheme (RGC/ECS, HKSAR), Janssen, and Pfizer, internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme and Pfizer, outside the submitted work; Eric Y.F. Wan reports grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region and the Hong Kong Research Grants Council, outside the submitted work; Celine S.L. Chui reports grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, and Amgen and personal fees from PrimeVigilance, outside the submitted work; Wallis C.Y. Lau reports receiving grants from AIR@InnoHK administered by the Innovation and Technology Commission of Hong Kong, outside the submitted work; Esther W. Chan reports grants from Research Grants Council of Hong Kong, Research Fund Secretariat of the Food and Health Bureau of Hong Kong, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda and Narcotics Division of the Security Bureau of Hong Kong; honorarium from Hospital Authority, outside the submitted work; Ian C.K. Wong reports grants from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK and Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund in Hong Kong, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, consulting fees from IQVIA, payment for expert testimony and is an independent non-executive director of Jacobson Medical in Hong Kong, outside of the submitted work; no other relationships or activities that could appear to have influenced the submitted work. Hao Luo reports grants from the Research Grants Council of Hong Kong, outside the submitted work; All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Risk of developing outcome events among individuals with COVID-19 in the short-term observation period (within 6 months)
Fig. 2
Fig. 2
Risk of developing outcome events among individuals with COVID-19 in the medium-term observation period (6 months to 1 year)
Fig. 3
Fig. 3
Risk of developing outcome events among individuals with COVID-19 in the long-term observation period (1 year to 2 years)
See this image and copyright information in PMC

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