Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis

Background Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19. Methods Three medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects. Results A total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1-43.3]), anorexia (30.0% [23.2-36.9]), dyspnea/shortness of breath (26.9% [19.2-34.6]), and malaise (26.7% [13.3-40.1]). The common specific neurological symptoms included olfactory (35.7-85.6%) and gustatory (33.3-88.8%) disorders, especially in mild cases. Guillain-Barre syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19. Conclusions Neurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms.