Post-Acute Sequelae of COVID-19 Across 15 Major Health Domains and 67 Diseases in Individuals With Depressive Disorder: A Korean Nationwide Cohort Study.

backgroundIndividuals with depressive disorder often face barriers in accessing healthcare; however, research on the acute and post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in this population remains limited. We aimed to investigate the risk of PASC in individuals with depressive disorder.

methodsWe used a longitudinal, large-scale, population-based cohort from South Korea, including individuals aged ≥ 20 years with depressive disorder and confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between January 1, 2020 and December 31, 2022. Individuals were followed from the date of COVID-19 diagnosis (index date) until the occurrence of each outcome, which included 15 major health domains and 67 specific diseases defined based on the International Classification of Diseases, 10th edition (ICD-10) codes. To reduce bias, we applied 1:1 propensity score matching and estimated the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. Subgroup analyses were conducted based on COVID-19 severity (mild vs. moderate-to-severe), vaccination status, and time-dependent risk patterns (< 3, 3-6, 6-12, and ≥ 12 months).

resultsThe study included 722,088 individuals with depressive disorder (mean age, 44.10 [standard deviation, 11.80] years; 61.65% female). In individuals with depressive disorder, SARS-CoV-2 infection was associated with an elevated risk of postacute sequelae across 14 of 15 major health domains, including infections (aHR, 1.27; 95% CI, 1.24-1.30), respiratory disorders (aHR, 1.54; 95% CI, 1.49-1.59), and circulatory/respiratory symptoms (aHR, 1.34; 95% CI, 1.31-1.37). Among 67 specific conditions, 35 showed significantly elevated risks, including malnutrition (aHR, 1.31; 1.13-1.53), chronic obstructive pulmonary disease (aHR, 1.54; 95% CI, 1.49-1.59), asthma (aHR, 1.61; 95% CI, 1.54-1.68), and vascular intestinal disorders (aHR, 1.38; 95% CI, 1.03-1.85). The risks peaked within the first 3 months postinfection and gradually declined over time. Severe COVID-19 was associated with increased risks compared to mild cases, particularly for blood disorders (aHR, 3.14; 95% CI, 2.84-3.48), and self-harm (aHR, 14.83; 95% CI, 6.52-33.71).

conclusionIn individuals with depressive disorder, SARS-CoV-2 infection is associated with a higher risk of developing post-acute sequelae across nearly all health domains and more than half of the specific conditions. Targeted surveillance and tailored intervention strategies are needed to mitigate long-term health consequences.