Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19

Abstract

Abstract Background A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3–6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Methods Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Results Elevated GFAp is associated to the development of mild cognitive dysfunction at follow-up (p = 0.01), especially in women (p = 0.005). Patients experiencing different dimensions of fatigue at follow-up had significantly lower GFAp, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL was lower in patients experiencing reduced motivation (p = 0.004). Conclusion Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19. Trial registration: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).