Inflammatory and mental health sequelae of COVID-19

The COVID-19 pandemic has caused significant negative consequences to mental health. Increased inflammatory factors and neuropsychiatric symptoms, such as cognitive impairment ("brain fog"), depression, and anxiety are associated with long COVID [post-acute sequelae of SARS-CoV-2 infection (PASC), termed neuro-PASC]. The present study sought to examine the role of inflammatory factors as predictors of neuropsychiatric symptom severity in the context of COVID-19. Adults (n = 52) who tested negative or positive for COVID-19 were asked to complete self-report questionnaires and to provide blood samples for multiplex immunoassays. Participants who tested negative for COVID-19 were assessed at baseline and at a follow-up study visit (similar to 4 weeks later). Individuals without COVID-19 reported significantly lower PHQ-4 scores at the follow-up visit, as compared to baseline (p = 0.03; 95% CI-1.67 to -0.084). Individuals who tested positive for COVID-19 and experienced neuro-PASC had PHQ-4 scores in the moderate range. The majority of people with neuro-PASC reported experiencing brain fog (70% vs. 30%). Those with more severe COVID-19 had significantly higher PHQ-4 scores, as compared to those with mild disease (p = 0.008; 95% CI 1.32 to 7.97). Changes in neuropsychiatric symptom severity were accompanied by alterations in immune factors, particularly monokine induced by gamma interferon (IFN-gamma) (MIG, a. k.a. CXCL9). These findings add to the growing evidence supporting the usefulness of circulating MIG levels as a biomarker reflecting IFN-gamma production, which is important because individuals with neuro-PASC have elevated IFN-gamma responses to internal SARS-CoV-2 proteins.