Neuroinvasive potential of a primary respiratory pathogen SARS- CoV2: Summarizing the evidences

Abstract

Backround and aims: After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus (COVID-19) affected patients are high fever, dry-cough, dyspnoea, lethal pneumonia whereas some patients also show additional neurological signs such as headache, nausea, vomiting etc. The accumulative evidences suggest that SARS-CoV-2 is not only confined within the respiratory tract but may also invade the central nervous system (CNS) and peripheral nervous system (PNS) inducing some fatal neurological diseases. Here, we analyze the phylogenetic perspective of SARS-CoV-2 with other strains of β-Coronaviridae from a standpoint of neurological spectrum disorders.

Methodology: A Pubmed/Medline, NIH Lit Covid, Cochrane library and some open data bases (BioRxiv, MedRxiv,preprint.org and others) search were carried out by using keywords relevant to our topic of discussion. The extracted literatures are scrutinized by the authors.

Results: 58 literatures including original articles, case reports and case series were selected by the authors to analyze the differential distribution of neurological impairments in COVID-19 positive patients along with angiotensin-converting enzyme-2 (ACE2) expression dynamics in neuronal and non-neuronal tissue in CNS and PNS with neuroinvasive potential of SARS-CoV2.

Conclusion: We discuss the need for modulations in clinical approach from a neurological point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV2 positive patients.

Keywords: ACE2; CNS; COVID-19; Coronavirus; Neurological disorders; PNS; Phylogenetic perspective; SARS-CoV2.

Fig. 1

A. Phylogenetic network showing receptor binding domains from various betacoronaviruses. The star denotes nCoV-19 and the question marks means unknown receptor used by the viruses.B,C,D depict structural comparison of the receptor binding domain of SARS- CoV,nCoV-19,MERS-CoV binding to their own receptors respectively. Magenta colour represents core domain and the external subdomains of SARS-CoV,nCoV-19,MERS CoV are represented by orange, blue and green respectively [9].

Fig. 2

Based on the manually curated knowledge in UniProtKB and via automatic text mining of the biomedical literature,tissue associations are derived. The confidence of each association is signified by stars, where ★★★★★ is the highest confidence and ★☆☆☆☆ is the lowest. Each tissue–gene association is represented on a text-mining score, which is proportional to 1) the absolute number of comentionings and 2) the ratio of observed to expected comentionings (i.e. the enrichment). These scores are normalized to z-scores by comparing them to a random background. This is represented by stars, each star corresponding to two standard deviations above the mean of the background distribution [TISSUE2.0].