COVID-19 and the subsequent risk of mental disorders: A nationwide study of all SARS-CoV-2 PCR test results in Denmark

IMPORTANCE: Psychiatric outcomes after COVID-19 have been of high concern during the pandemic, however, studies on a nation-wide level are lacking. OBJECTIVE: To examine the risk of mental disorders and use of psychotropic medication among individuals with COVID-19 compared to individuals not tested, individuals tested SARS-CoV-2 negative and those hospitalized for non-COVID infections. DESIGN, SETTING AND PARTICIPANTS: Nation-wide cohort study using Danish registries to identify all individuals alive, ≥18 years and resident in Denmark between January-March-2020 (N=4,152,792), excluding everyone with a previous history of a mental disorder (N=616,546). EXPOSURES: SARS-CoV-2 PCR testing (negative, positive, and never tested) and COVID-19 hospitalization. MAIN OUTCOMES AND MEASURES: Risk of new-onset mental disorders and redeemed psychotropic medication was estimated through survival analysis using a Cox proportional hazard model reporting hazard rate ratios (HRR) with 95% confidence intervals (CI) as measures of relative risk. All outcomes were adjusted for age, sex, parental history of mental illness, Charlson-Comorbidity-Index, education-level, income, and job-status. RESULTS: A total of 526,749 individuals tested positive for SARS-CoV-2, while 3,124,933 tested negative and 501,110 had no tests performed. The risk of mental disorders was increased in individuals tested positive, respectively, negative for SARS-CoV-2 (HRR, 1.24; 95%CI, 1.17-1.31, respectively, HRR, 1.42; 95%CI, 1.38-1.46), compared to those never tested. Compared to individuals tested negative, the risk of new-onset mental disorders in SARS-CoV-2 positive individuals was lower in the 18-29yrs age-group (HRR, 0.75; 95%CI, 0.69-0.81), whereas individuals >70-years had 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 18-29 years age-group (HRR, 0.81; 95%CI, 10.76-0.85) and elevated risk in those >70yrs (HRR, 1.57; 95%CI, 1.45-1.70). The risk for new-onset mental disorders were substantially elevated in hospitalized COVID-19 patients compared to the general population (HRR, 2.52; 95%CI, 2.34-2.72); however, no difference in risk was seen when compared to hospitalization for non-COVID respiratory infections (HRR, 1.03; 95%CI, 0.82-1.29). CONCLUSION AND RELEVANCE: In this nation-wide cohort study, overall risk of new-onset mental disorders in SARS-CoV-2 positive did not exceed the risk among individuals tested negative (except for those >70yrs). However, when hospitalized, COVID-19 patients had markedly increased risk compared to the general population, but comparable to those hospitalized for non-COVID infections.