Delirium as a marker of systemic vulnerability in hospitalized patients with COVID-19: a multicenter cohort study with extended follow-up

Delirium is a common neuropsychiatric complication in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to short-term mortality. However, its long-term prognostic significance and whether it independently contributes to death remain unclear. This multicenter cohort study aimed to identify the risk factors for delirium and evaluate their prognostic significance. This retrospective cohort study included 1,030 patients with COVID-19 at two tertiary hospitals in Seoul and Gyeonggi-do, South Korea (January 2021 to December 2022), excluding those with prior dementia. Delirium was assessed using the Confusion Assessment Method and diagnosed according to DSM-5 criteria. Logistic regression was used to identify the risk factors for delirium. Kaplan-Meier analysis and Cox regression were used to evaluate survival. Among 1,030 patients (mean age 62.9 years, 44.4% women), 119 (11.6%) developed delirium and 264 (25.8%) died. Mortality was significantly higher in the delirium group (47.1% vs. 23.0%, p < 0.001). Independent risk factors for delirium were advanced age (OR 1.03, 95% CI 1.02–1.05), higher COVID-19 severity (OR 3.41, 95% CI 2.56–4.53), and pre-admission antipsychotic use (OR 3.52, 95% CI 1.44–8.63). Unadjusted survival was shorter in the delirium group (18.0 vs. 25.6 months, p < 0.001), but after multivariable adjustment, delirium did not independently predict mortality (HR 1.33, 95% CI 0.89–2.00, p = 0.16). Mortality was significantly associated with older age, comorbidity burden, COVID-19 severity, and the use of opioids and antiepileptic medication. Delirium reflects systemic vulnerability rather than being a direct determinant of mortality. Early identification and proactive management of patients at high risk of delirium may improve long-term outcomes.