BACKGROUND: SARS-CoV-2 is a neurotrophic and pro-inflammatory virus, with several acute and more persistent neuropsychiatric sequelae reported. There are limited data from African cohorts and few acute illness biomarkers of persistent neuropsychiatric symptoms. OBJECTIVES: To examine the association of neuropsychiatric outcomes with clinical illness severity, systemic inflammation, cardiovascular and renin-angiotensin-system (RAS) biomarkers. Second, to determine the prevalence of neuropsychiatric symptoms in a cohort of South African SARS-CoV-2 PCR positive patients at least six months following infection/hospitalization. METHODOLOGY: SARS-CoV-2 PCR positive patients were recruited prospectively from Cape Town, South Africa, including hospitalized patients from ancestral, beta and delta-dominant COVID-19 waves (pre-vaccine rollout)
and asymptomatic/mild SARS-CoV-2 positive patients. The 96-protein O-link inflammation and cardiovascular panels, RAS fingerprinting, and antibody responses were measured in serum samples collected at peak severity and recovery (>
3 months post-infection). Telephonic interviews were conducted at least six months post infection/hospitalization. Validated measures employed were: WHO Self-Report Questionnaire (SRQ-20), Generalized Anxiety Disorder Scale (GAD-7), Chalder Fatigue Scale (CFS-11) and Telephonic Montreal Cognitive Assessment (T-MoCA). RESULTS: Ninety-seven participants completed telephonic interviews. The median (IQR) age was 48 (37-59) years, and 54 % were female. There were no significant associations between neuropsychiatric outcomes and illness severity, systemic inflammation, cardiovascular and/or renin-angiotensin-system (RAS) biomarkers from either peak illness or recovery samples. More than half of this SA COVID-19 cohort had one or more persistent neuropsychiatric symptoms >
6 months post vaccine-naïve infection. On the T-MoCA, 44 % of participants showed evidence of cognitive and/or memory impairments. CONCLUSION: The high prevalence of persistent neuropsychiatric symptoms in this African cohort supports ongoing attention to long COVID. Acute and early serum protein biomarkers were not associated with persistent neuropsychiatric outcomes post-COVD-19.