Clinical Manifestations

BACKGROUND: There is a paucity of data comparing neuropsychiatric testing in patients with post-acute COVID-19 symptoms ("long-COVID") to COVID-19 patients without long-term symptoms and to COVID-19 negative controls. METHOD: We conducted a cross-sectional study of patients with and without prior laboratory-confirmed COVID-19 (COV+ vs COV-), who had no previous history of dementia/cognitive impairment. Long-COVID was defined as subjective symptoms (WHO symptom questionnaire) lasting >1 month after index SARS-CoV-2 infection. All patients underwent UDS3 neuropsychiatric testing and received a formal cognitive diagnosis (with respective etiology following NACC criteria) by a consensus group of physicians blinded to their long-COVID status as: normal, mild-cognitive impairment (MCI), or dementia. Cognitive test scores, CDR, and physician diagnoses were compared between patients with and without long-COVID using Fisher's exact and Mann-Whitney U tests and multivariable logistic regression models were constructed to adjust for differences in age, sex, time from initial COVID diagnosis and number of COVID-19 infections. RESULT: We enrolled 279 patients: N = 51 (18%) COV-, N = 228 (82%) COV+, N = 122 (44%) with long-COVID, median age 70 years (IQR 63-76), and 62% female. Compared to COV- subjects and COV+ subjects without long-COVID, participants with long-COVID had significantly worse cognitive test results (≥1 cognitive battery abnormal in 64% with long-COVID compared to 46% without, p = 0.003), as well as worse global CDR and CDR sum of boxes scores (26% CDR>0 among long-COVID vs. 6% without long-COVID, p <0.001). Significantly more long-COVID patients were diagnosed with MCI or dementia (25% vs. 6% without long-COVID, p <0.001), including higher proportions with MCI related to Alzheimer's disease (10% vs. 3%, p = 0.038), and MCI related to psychiatric diagnoses (11% vs. 1%, p <0.001). After adjusting for sex, age, time from initial COVID diagnosis and number of COVID-19 infections, long-COVID was associated with significantly higher odds of an MCI diagnosis (aOR 3.5, 95% CI 1.2-10.6, p = 0.025), and specifically MCI due to Alzheimer's (aOR 4.4, 95% CI 1.1-18.3, p = 0.041), but not MCI due to psychiatric disease. CONCLUSION: Long-COVID patients had significantly worse cognitive test scores and higher rates of MCI (Alzheimer's type) diagnoses compared to both COV- and COV+ subjects without long-COVID symptoms.