Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for COVID-19 in Brazil

Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil. Months after hospital admission (mean = 168.45 +/- 90.31 days; range = 75.00-365.00 days), COVID-19 survivors (n = 72) presented significant difficulties in tests tapping global cognition, episodic memory, working memory and inhibitory control relative to controls and to validated normative scores. A considerable proportion of participants suffered from fatigue (36.1 %), anxiety (27.8 %), and depressive symptoms (43.1 %). Elevated blood levels of TNF-alpha, during hospitalization, and TNF-alpha and IL-1 beta, at follow-up, correlated with changes in brain microstructural diffusion indices (beta = 0.144, p = 0.005). These neuroimaging markers were associated with decreased episodic memory (beta = -0.221, p = 0.027), working memory (beta = -0.209, p = 0.034) and inhibitory control (beta = -0.183, p = 0.010) at follow-up. Severity of depressive symptoms correlated with deficits in global cognition in post-COVID-19 cases (beta = -0.366, p = 0.038). Our study provides preliminary evidence that longterm cognitive dysfunction following COVID-19 may be mediated by brain microstructural damage, triggered by persistent neuroinflammation. In addition, depressive symptoms may contribute to prolongated global cognitive impairments in those cases.