Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19

ObjectiveThis study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events.MethodsA systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle-Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results.ResultsNine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality.ConclusionsDifferent neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.

Automated summary

This study synthesized existing evidence on biomarkers related to neurological events in COVID-19 patients. The most frequently assessed biomarkers were neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). While these biomarkers were correlated with disease severity and outcomes, they were not necessarily associated with neurological events.