Association between mental health symptoms and autoimmunity in patients with long COVID

Neuropsychiatric symptoms are common features in long COVID. The pathogenesis of neuropsychiatric manifestations in both acute COVID-19 and long COVID remains unclear. This study aimed to examine mental health symptoms-depressive, anxiety, and insomnia symptoms-in COVID-19 survivors with long COVID, and to explore their potential association with autoimmune activity.

We conducted an observational, cross-sectional study of 228 adults recruited from a long COVID program in Cartagena, Colombia. Participants underwent clinician-administered interviews and completed validated psychometric scales to assess depressive (PHQ-9), anxiety (GAD-7), and insomnia (ISI) symptoms. Sociodemographic, clinical, and biological data were collected. The autoantibody panel included antinuclear antibodies (ANA), anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Smith (Sm), rheumatoid factor (RF), anti-thyroglobulin (Tg), and anti-thyroid peroxidase (TPO), measured via ELISA and immunofluorescence. Robust logistic regression models were used to evaluate associations between long COVID, autoantibody positivity, and mental health symptoms, adjusting for age, sex, and relevant covariates.

57% of participants with a history of COVID-19 acute infection reported long COVID. In participants with long COVID, we reported high proportions of depressive (21.2%), anxiety (31.2%), and insomnia (28.7%) symptoms. Moreover, an association of all three mental health symptoms with autoantibody positivity (particularly antinuclear antibodies [ANA] isolated or co-occurring with anti-TPO antibodies) was observed in individuals with long COVID. Our findings suggest a potential association between psychopathological symptoms, autoantibody positivity, and distinct clinical profiles of long COVID, warranting further longitudinal investigation.

Mental health symptoms (MHS) should be considered one of the main targets involved in translational research in long COVID. There is an urgent need for consultation-liaison physicians to work closely with immunologists, rheumatologists, and pain medicine physicians in clinical settings as well as in research. This will contribute to a better understanding of the impact of MHS during illness in long COVID variants.