ABSTRACT
Importance: Psychiatric outcomes after COVID-19 have been of high concern during the pandemic; however, studies on a nationwide level are lacking. Objective: To 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 Participants: This 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 = 4â¯152â¯792), excluding individuals with a mental disorder history (n = 616â¯546), with follow-up until December 31, 2021. Exposures: Results of SARS-CoV-2 polymerase chain reaction (PCR) testing (negative, positive, and never tested) and COVID-19 hospitalization. Main Outcomes and Measures: Risk 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. Results: A total of 526â¯749 individuals had positive test results for SARS-CoV-2 (50.2% men; mean [SD] age, 41.18 [17.06] years), while 3â¯124â¯933 had negative test results (50.6% women; mean [SD] age, 49.36 [19.00] years), and 501â¯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 Relevance: In 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.
ABSTRACT
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.
ABSTRACT
Importance: Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking. Objective: To investigate cognitive impairment, neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness. Design, Setting, and Participants: This prospective case-control study from a tertiary referral hospital in Copenhagen, Denmark, conducted between July 2020 and July 2021, followed up hospitalized COVID-19 survivors and control patients hospitalized for non-COVID-19 illness, matched for age, sex, and intensive care unit (ICU) status 6 months after symptom onset. Exposures: Hospitalization for COVID-19. Main Outcomes and Measures: Participants were investigated with the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semi-structured interview for subjective symptoms. Primary outcomes were total MoCA score and new onset of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results. All outcomes were adjusted for age, sex, ICU admission, admission length, and days of follow-up. Secondary outcomes were adjusted for multiple testing. Results: A total of 85 COVID-19 survivors (36 [42%] women; mean [SD] age 56.8 [14] years) after hospitalization and 61 matched control patients with non-COVID-19 illness (27 [44%] women, mean age 59.4 years [SD, 13]) were enrolled. Cognitive status measured by total geometric mean MoCA scores at 6-month follow-up was lower (P = .01) among COVID-19 survivors (26.7; 95% CI, 26.2-27.1) than control patients (27.5; 95% CI, 27.0-27.9). The cognitive status improved substantially (P = .004), from 19.2 (95% CI, 15.2-23.2) at discharge to 26.1 (95% CI, 23.1-29.1) for 15 patients with COVID-19 with MoCA evaluations from hospital discharge. A total of 16 of 85 patients with COVID-19 (19%) and 12 of 61 control patients (20%) had a new-onset psychiatric diagnosis at 6-month follow-up, which was not significantly different (odds ratio, 0.93; 95% CI, 0.39-2.27; P = .87). In fully adjusted models, secondary outcomes were not significantly different, except anosmia, which was more common after COVID-19 (odds ratio, 4.56; 95% CI, 1.52-17.42; P = .006); but no longer when adjusting for multiple testing. Conclusions and Relevance: In this prospective case-control study, cognitive status at 6 months was worse among survivors of COVID-19, but the overall burden of neuropsychiatric and neurologic signs and symptoms among survivors of COVID-19 requiring hospitalization was comparable with the burden observed among matched survivors hospitalized for non-COVID-19 causes.