Background: Neuropsychiatric manifestations are a recognized complication of COVID-19, yet their temporal evolution across pandemic waves remains poorly characterized in hospitalized cohorts. This study examined whether their prevalence and composition changed across five successive waves. Methods: We conducted a retrospective observational study of 1471 hospitalized adults with confirmed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Sibiu County Emergency Clinical Hospital, Romania (March 2020–January 2025), spanning ancestral through Omicron variants. A custom natural language processing pipeline extracted symptoms, medications, and International Classification of Diseases, 10th Revision (ICD-10) codes from electronic medical records. Nine hierarchical clinical clusters were defined; temporal trends were assessed using multivariable logistic regression with age-stratified replication. Results: Severe neurological presentations (stroke, seizures, hemiparesis) increased six-fold from 3.5% in Wave 1 to 20.1% in Wave 5, while psychiatric symptoms (anxiety, insomnia) declined from 13.3% to 4.3%. Overall, neuropsychiatric burden remained stable (~40–45%), revealing a compositional shift. This neurological trend persisted after multivariable adjustment (adjusted odds ratio 4.34, for Wave 5 vs. Wave 1) and within age-stratified subgroups, was inversely associated with respiratory severity and could not be attributed to vaccination status. The composite neurological severity index independently predicted mortality and intensive care unit admission. Conclusions: Neuropsychiatric manifestations in hospitalized Coronavirus disease of 2019 (COVID-19) patients underwent a compositional shift from psychiatric dominance in early waves to severe neurological dominance in later waves, consistent with a transition from reactive psychiatric presentations toward progressive neurological injury. This pattern, largely independent of measured confounders, underscores the need for sustained neurological surveillance beyond the acute respiratory phase.
Lupu et al. (2026) studied this question.