COVID-19 and Risk for Mental Disorders Among Adults in Denmark
Authors: Nersesjan Vardan , Christensen Rune H. B. , Kondziella Daniel , Benros Michael E. 
Published: May 2023

ImportancePsychiatric outcomes after COVID-19 have been of high concern during the pandemic; however, studies on a nationwide level are lacking.ObjectiveTo estimate the risk of mental disorders and use of psychotropic medication among individuals with COVID-19 compared with individuals not tested, individuals with SARS-CoV-2–negative test results, and those hospitalized for non–COVID-19 infections.Design, Setting, and ParticipantsThis nationwide cohort study used Danish registries to identify all individuals who were alive, 18 years or older, and residing in Denmark between January 1 and March 1, 2020 (N = 4 152 792), excluding individuals with a mental disorder history (n = 616 546), with follow-up until December 31, 2021.ExposuresResults of SARS-CoV-2 polymerase chain reaction (PCR) testing (negative, positive, and never tested) and COVID-19 hospitalization.Main Outcomes and MeasuresRisk of new-onset mental disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes F00-F99) and redeemed psychotropic medication (Anatomical Therapeutic Chemical classification codes N05-N06) was estimated through survival analysis using a Cox proportional hazards model, with a hierarchical time-varying exposure, reporting hazard rate ratios (HRR) with 95% CIs. All outcomes were adjusted for age, sex, parental history of mental illness, Charlson Comorbidity Index, educational level, income, and job status.ResultsA total of 526 749 individuals had positive test results for SARS-CoV-2 (50.2% men; mean [SD] age, 41.18 [17.06] years), while 3 124 933 had negative test results (50.6% women; mean [SD] age, 49.36 [19.00] years), and 501 110 had no tests performed (54.6% men; mean [SD] age, 60.71 [19.78] years). Follow-up time was 1.83 years for 93.4% of the population. The risk of mental disorders was increased in individuals with positive (HRR, 1.24 [95% CI, 1.17-1.31]) and negative (HRR, 1.42 [95% CI, 1.38-1.46]) test results for SARS-CoV-2 compared with those never tested. Compared with individuals with negative test results, the risk of new-onset mental disorders in SARS-CoV-2–positive individuals was lower in the group aged 18 to 29 years (HRR, 0.75 [95% CI, 0.69-0.81]), whereas individuals 70 years or older had an increased risk (HRR, 1.25 [95% CI, 1.05-1.50]). A similar pattern was seen regarding psychotropic medication use, with a decreased risk in the group aged 18 to 29 years (HRR, 0.81 [95% CI, 0.76-0.85]) and elevated risk in those 70 years or older (HRR, 1.57 [95% CI, 1.45-1.70]). The risk for new-onset mental disorders was substantially elevated in hospitalized patients with COVID-19 compared with the general population (HRR, 2.54 [95% CI, 2.06-3.14]); however, no significant difference in risk was seen when compared with hospitalization for non–COVID-19 respiratory tract infections (HRR, 1.03 [95% CI, 0.82-1.29]).Conclusion and RelevanceIn this Danish nationwide cohort study, overall risk of new-onset mental disorders in SARS-CoV-2–positive individuals did not exceed the risk among individuals with negative test results (except for those aged ≥70 years). However, when hospitalized, patients with COVID-19 had markedly increased risk compared with the general population, but comparable to risk among patients hospitalized for non–COVID-19 infections. Future studies should include even longer follow-up time and preferentially include immunological biomarkers to further investigate the impact of infection severity on postinfectious mental disorder sequelae.