Journal Article

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

Mehra, Reena, Zhou, Yadi, Shen, Jiayu, Jehi, Lara, Cheng, Feixiong, Hou, Yuan

2021

Overview

The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood. The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study. In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response, and procoagulant state C-reactive protein (CRP), Procalcitonin (PCT), and coagulation indicator (D-dimer) in patients with COVID-19. Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke. Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations. We found that the overall pooled prevalence of stroke history was 2.98% (95% CI, 1.89–4.68; I 2 =69.2%) in the COVID-19 population. Notably, the severe group had a higher prevalence of stroke (6.06%; 95% CI 3.80–9.52; I 2 = 42.6%) compare to the non-severe group (1.1%, 95% CI 0.72–1.71; I 2 = 0.0%). There were increased levels of CRP, PCT, and D-dimer in severe illness, and the pooled mean difference was 40.7 mg/L (95% CI, 24.3–57.1), 0.07 μg/L (95% CI, 0.04–0.10) and 0.63 mg/L (95% CI, 0.28–0.97), respectively. Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses. RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations. In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i.e., VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: C-reactive protein / Cardiomyocytes / Cell adhesion molecules / Cerebrovascular disease / Coronaviridae / coronavirus disease 2019 (COVID-19) / Coronaviruses / COVID-19 / Epidemiology / Experiments / Gene expression / Inflammation / Kinases / Mass spectrometry / Meta-analysis / Nervous system / network medicine / Neuroscience / Pneumonia / Procalcitonin / protein-protein interactome / Proteins / Ribonucleic acid / RNA / Sample size / SARS-CoV-2 / Scientific imaging / Severe acute respiratory syndrome coronavirus 2 / Stroke / Vascular cell adhesion molecule 1