Post‐Omicron cognitive decline is largely reversible: Two‐year multicenter cohort study of domain‐specific outcomes in hospitalized patients

Abstract Background Cognitive impairment represents a significant concern within the spectrum of post‐acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection, particularly impacting the aging population. This study aimed to assess the incidence of reversible and irreversible cognitive decline after Omicron infection, identify changes in specific cognitive domains, and determine the risk factors for progressive cognitive decline. Methods In this multicenter longitudinal cohort, 3419 patients diagnosed with Coronavirus Disease 2019 (COVID‐19) between December 2022 and March 2023 from nine hospitals in China were enrolled. Cognitive function was assessed at 6 months and 2 years post‐infection using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Telephone Interview of Cognitive Status‐40 (TICS‐40). Domain‐specific performance was analyzed, and logistic regression was used to identify risk factors. Results In total, 2087 patients with COVID‐19 completed both the 6‐month and 2‐year follow‐up (1172 [56.2%] men; 915 [43.8%] women; median age 63.0 years [interquartile range]: 53.0–71.0) respectively. Two years after discharge from the hospital, 67.1% (1401/2087) of survivors maintained stable cognitive function, 22.0% (460/2087) of survivors experienced reversible cognitive decline, and 10.8% (226/2087) experienced irreversible cognitive decline (3.6% [76/2087] showed progressive cognitive decline). The profile of recovery or deterioration in cognitive domains involved attention/calculation, executive function, delayed recall, registration, and learning, all of which are multi‐dimensional. Age ≥60 years (OR = 4.31, 95% CI [1.47, 12.65]), reinfection (OR = 2.12, 95% CI [1.33, 3.38]), and vaccination doses (OR = 0.69, 95% CI [0.55, 0.87]) were associated with progressive decline. Conclusion Post‐Omicron cognitive decline is largely reversible, with significant recovery observed in key domains including attention/calculation, executive function, delayed recall, registration, and learning. However, a vulnerable subset with risk factors such as older adults, reinfection, and inadequate vaccination, is at risk for progressive cognitive decline. These findings highlight the necessity of targeted long‐term monitoring and early intervention for high‐risk populations.