Science News: Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-Analysis

Submitted by:  Niranjan Singh, MD, DM
Edited by: Sarah Chen, MD

Misra S, Kolappa K, Prasad M, et al. Frequency of neurologic manifestations in COVID-19: A systematic review and meta-analysis. Neurology. 2021;97(23):e2269-e2281

Summary: More than 1 year into the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has caused more than 200 million cases and 4.28 million deaths across 220 countries as of August 9, 2021. This article is a systemic review and meta-analysis to obtain pooled prevalence estimates to understand the variation in reported frequencies of various neurologic manifestations in patients with COVID-19 across different groups in literature published from December 31, 2019, to December 15, 2020. 

Out of 2,455 articles cited, only 350 articles met the authors’ inclusion criteria and were included for review. The study included data from 145,721 patients with COVID-19 from 55 countries, 89% of whom were hospitalized. They identified total of 41 neurologic manifestations including 24 symptoms and 17 diagnoses. Most common neurologic symptoms include fatigue (32%), myalgia (20%), smell impairment (19%), taste impairment (21%), headache (13%) and dizziness (7%). Stroke was the most common neurological diagnosis with pooled prevalence of 2%. Among stroke, acute ischemic stroke or TIA accounted for 1% and hemorrhagic stroke 0.31% and cerebral venous thrombosis 0.12%. Very low prevalence was seen for cranial nerves/polyneuropathy 1%, GBS 0.28%, encephalitis 0.3%. In patients over 60 year old, they could present with acute confusion or delirium (34%). 

Patients with severe COVID-19 were less likely than those with mild disease to have alteration of smell. There seemed to be no significant association was found between other neurologic manifestations with COVID-19 severity. 

Overall, approximately up to one-third of patients with COVID-19 analyzed in this review experienced at least one neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of any neurologic manifestations in this age group was associated with higher mortality.

Comments: 89% of the data came from hospitalized patients in this study. This cannot be applied to community prevalence of neurologic manifestation of COVID-19, which includes mostly non hospitalized patients. It appeared that smell impairment (50%), taste impairment (45%), headache (31%), and myalgia (31%) were found to be more common in non-hospitalized cases, while fatigue (31%) was found to be more common in hospitalized patients.

This study showed that the presence of impairment of taste and smell has inverse relationship to severity of the illness. Explanations provided include inflammation around olfactory nerve presenting spread of virus or poor reporting in sick patients. Multiple mechanisms were proposed leading to neurologic manifestations including hypoxia, cytokine storm, autoimmune response, hypercoagulability, endotheliopathy, and multi-organ failure.

This is an observational study, thus it has limitation of its bias. In addition, the literature review of this article only covered until December 2020. The pandemic has changed significantly over time with different variants and it demands more recent literature review and updated analysis.

Articles of similar interest: 
Safonova A, Paul N, Altamirano V, et al. Neurologic manifestations associated with COVID-19 in hospitalized patients. Neurology. 2021;96(no. 15 Supplement 1718)

Badii M, Poursheykhi M, Shivaprasad A, Smith R, Shroff S. Neurological manifestations of COVID-19. Neurology. 2021;96(no. 15 Supplement 4987)