Sex-stratified neuropsychiatric manifestations of post-COVID-19 condition: A Japanese National Registry of clinical and patient-reported outcomes (PSCORE-J)

Aim To establish and characterize neuropsychiatric manifestations of post-COVID-19 condition (PCC) through Japan's first nationwide registry integrating clinical assessments with patient-reported outcomes. Methods The Psychiatric Symptoms for COVID-19 Registry Japan collected data between December 2022 and September 2024, integrating electronic patient-reported outcomes ( n = 806) with in-person clinical assessments ( n = 136). Participants were classified as cases or tolerant controls following WHO criteria. The Composite Psychological Burden Score (CPBS) was constructed using principal component analysis of depression, anxiety, insomnia, cognitive dysfunction, and quality of life measures (accounting for 75.4% of variance). Sex-stratified multivariate analyses examined risk factors. Results Clinical evaluation revealed neurological symptoms (34.1%) as predominant manifestations, followed by pain-related symptoms (23.5%). PCC cases showed significantly higher rates of physical and psychiatric comorbidities, impaired quality of life, and work discontinuation (52.9%). Patient-reported perception of significant life changes due to PCC was most strongly associated with physician-diagnosed PCC (odds ratio [OR]: 11.2), followed by CPBS (OR: 6.25 per standard deviation, 95% CI: 2.48–15.7). Longer COVID-19 infection duration, unemployment, and reduced family communication were significant in both sexes. In sex-stratified analyses, psychiatric comorbidity (adjusted OR [aOR]: 5.68) and single status (aOR: 4.46) were significant in men and reduced outdoor activity in women (aOR up to 12.6); however, no interaction with sex reached significance, indicating that these sex differences were not statistically confirmed. Conclusion Integrating subjective disease perception with psychological, cognitive, and quality of life measures may improve identification of neuropsychiatric burden in PCC. The sex-stratified patterns warrant confirmation in larger cohorts.