Neurocognitive and Psychiatric Outcomes Following Mild to Moderate COVID-19: A Longitudinal Comparison of Alpha/Delta and Omicron Variants

Purpose: Cognitive complaints are a core feature of post-acute sequelae of COVID-19 (PASC), yet less is known about combined neurocognitive and psychiatric outcomes following infection with later variants such as Omicron. This study compared longitudinal neuropsychological performance and psychiatric distress following mild to moderate COVID-19 infection during the Alpha/Delta versus Omicron periods. Patients and methods:: Fifty-five adults with a history of mild to moderate COVID-19 infection participated in a longitudinal study. Participants infected during the Alpha/Delta waves (December 2020–November 2021; n = 27) were compared with those infected during the Omicron wave (February–May 2022; n = 28). Participants completed in-person neuropsychological assessments evaluating memory, processing speed, attention, and executive function, with impairment defined using standard clinical criteria. Psychiatric measures assessed symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and fatigue. Participants were reassessed approximately six months later. Group differences, comparisons to normative data, and longitudinal changes were analyzed. Results: At initial assessment, approximately half of participants in both groups demonstrated at least mild neuropsychological impairment. Both groups performed significantly below normative expectations on measures of immediate memory, while the Omicron group additionally showed reduced processing speed. No other cognitive domains differed from norms. At follow-up, impairment rates improved in both groups, and no test scores remained significantly below normative values; no participant demonstrated cognitive decline over time. Participants in the Alpha/Delta group reported more severe acute illness and greater medical comorbidity, though illness severity was mild to moderate in both groups. There were no significant between-group differences in depression, anxiety, PTSD, or fatigue. Conclusion: Neurocognitive performance improved over time following mild to moderate COVID-19 infection across both Alpha/Delta and Omicron variants, with no evidence of persistent deficits. Psychiatric distress and fatigue were similar across variants, suggesting generally favorable neuropsychiatric recovery trajectories.