Abstract
IMPORTANCE: Severe COVID-19 infection has been associated with neurological complications, but its role in accelerating cognitive decline remains unclear. OBJECTIVE: To determine whether individuals hospitalized for severe COVID-19 exhibit a higher incidence of new onset cognitive impairment compared to those hospitalized for other conditions. DESIGN: A retrospective study emulating a target trial using Mass General Brigham electronic health records (March 2020-August 2024). The causal effect of COVID-19 hospitalization was estimated via cumulative incidence functions accounting for the competing risk of death. SETTING: Multicenter hospital-based study across the Mass General Brigham healthcare system. PARTICIPANTS: A total of 221613 hospitalized patients met the eligibility criteria, including 6454 (2.0%) admitted due to COVID-19 and 215159 (98.0%) for all other conditions. Patients were excluded if they had less than three months of follow-up (due to censoring, cognitive impairment, or death), were younger than 55 years at baseline, or had no prior visit to Mass General Brigham in the year before baseline. MAIN OUTCOMES AND MEASURES: The primary outcome was new-onset cognitive impairment, identified via ICD codes and dementia medication prescriptions. The primary analysis estimated the hazard ratio for cognitive impairment with COVID-19 hospitalization relative to other hospitalizations, along with the risk difference at 4.5 years estimated via cumulative incidence functions. Inverse propensity score weighting was used to balance covariates (age, sex, comorbidities, hospitalization period). RESULTS: Among eligible patients (mean [SD] age, 69.55 [9.42] years, 55% female), those hospitalized for COVID-19 were significantly older and had more comorbidities (p < 0.05). COVID-19 hospitalization was associated with a higher risk of developing cognitive impairment (Hazard Ratio: 1.14 [95% CI: 1.02-1.30], P = 0.018). At 4.5 years, the cumulative incidence of cognitive impairment was 12.5% [95% CI: 11.3-13.5] in the COVID-19 group, compared to 11.6% [95% CI: 11.1-12.1] in the non-COVID-19 group. CONCLUSIONS AND RELEVANCE: Severe COVID-19 infection was associated with an elevated risk of developing clinically recognized cognitive impairment. Future studies are needed to validate findings in other health care settings. Early screening and intervention for cognitive decline may help optimize long-term outcomes for COVID-19 patients.