Postacute Sequelae of COVID-19 Across 12 Major Health Domains and 141 Diseases in Individuals With Mental Illness Among COVID-19 Survivors: A Population-Based Cohort Study in South Korea

Understanding whether individuals with mental illness, who face challenges related to healthcare barriers, are more vulnerable to postacute sequelae of COVID-19 is limited. Here, we investigated the potential association between pre-existing mental illness and postacute sequelae of COVID-19 across 12 major health domains and 141 specific diseases in COVID-19 survivors. The large-scale, population-based cohorts from South Korea (K-COV-N cohort) used in the study included 8 632 221 individuals aged 20 years or older who were infected with SARS-CoV-2 between January 1, 2020, and December 31, 2022. The risk of postacute sequelae of COVID-19 was assessed in the 1:2 propensity score-matched cohorts, comprising 12 major health domains and 141 diseases based on the ICD-10 code, following mental illness among patients with COVID-19. We assessed the time attenuation effect of major health outcomes after 30 days following SARS-CoV-2 infection. Multiple subgroup analyses were conducted by severity of mental illness, COVID-19 severity, vaccination, and SARS-CoV-2 strain. After 1:2 exposure-driven propensity score matching, we identified 1 341 320 participants with mental illness (mean age, 49.51 [SD, 13.82] years; 62.27% female) and 2 653 597 controls (mean age, 48.78 [SD, 13.75] years; 62.03% female). Individuals with mental illness exhibited significantly higher risks across all 12 major health domains, including: infectious and parasitic events (adjusted hazard ratio [aHR], 1.36 [95% CI, 1.33–1.38]), blood and immune-related events (1.21 [1.17–1.26]), endocrine, nutritional, and metabolic events (1.21 [1.18–1.24]), nerve-related events (2.13 [2.07–2.19]), eye-related events (1.29 [1.25–1.34]), ear and mastoid events (1.52 [1.50–1.54]), circulatory events (1.25 [1.17–1.35]), respiratory events (1.26 [1.24–1.29]), digestive events (1.41 [1.40–1.41]), skin-related events (1.34 [1.30–1.38]), musculoskeletal events (1.42 [1.41–1.43]), and genitourinary events (1.54 [1.18–2.01]). Of the 141 postacute sequelae of COVID-19, 133 showed significantly increased risks. The association was strongest within the first 6–12 months after SARS-CoV-2 infection, with risks progressively attenuating beyond 12 months and nearly disappearing after 18 months. Subgroup analysis revealed that individuals with mild mental illness exhibited higher aHRs for 11 of the 12 health outcome domains compared with those with severe mental illness. Altogether, our findings show the increased risk of postacute sequelae of COVID-19 across 12 major health domains in individuals with mental illness among COVID-19 survivors. These findings highlight the need for targeted monitoring and intervention strategies to address the vulnerabilities of this population, particularly during the post-COVID-19 period.