Calcitonin gene-related peptide: A biomarker for stroke in SARS-CoV-2 infection?

COVID-19 infection was mainly associated with respiratory symptoms, but lately, ischemic stroke (IS) has been reported in several cases. The incidence of IS in SARS-CoV-2 infection is increasing, and its mechanism is still not fully understood. Calcitonin gene-related peptide (CGRP) -the abundantly expressed protein in the peripheral and central nervous system- showed low expression in SARS-CoV-2 patients. This peptide is strongly implicated in regulating cerebral blood flow (CBF) and improving neurological deficits after cerebral arterial occlusion. We assume that a possible interplay between the low circulating levels of CGRP may affect CBF, thus worsening the symptoms of IS in SARS-CoV-2 patients.

Introduction

The association of Ischemic stroke (IS) and SARS-CoV-2 infection was reported with an occurrence of up to 4.9% during initial hospitalization [1]. However, the exact mechanism underlying these lesions remains unclear.

Calcitonin gene-related peptide (CGRP) is a vasoactive peptide released from sensory nerves and involved in attenuating cerebral ischemia, CGRP regulates the subfamilies of mitogen-activated protein kinase [2] and promote cell proliferation through the Wnt/β-catenin pathway as seen in the figure [3]. Therefore, CGPR can improve motor and sensitive functions after middle cerebral artery occlusion, as reported in an in vivo study [3]. Furthermore, besides its neuroprotective effects, CGRP has an anti-inflammatory role by reducing interleukin-2 production [4].

Recently a published case report by Aradi et al. 2019 indicated an association between CGRP antagonists and IS in young women; therefore, the decreased levels of CGRP might suppress its protective vasodilatory effect in cerebral arteries [5].

Interestingly, autopsies of SARS-CoV-2 infection cases revealed that nerve tissues are damaged [6]. In addition, Ochoa-Callejero et al. 2021 [4] observed that serum CGRP levels were significantly lower in 57 SARS-CoV-2 patients. Consequently, low CGRP levels might be correlated with cerebral vasospasm and ischemic lung lesions.

All the presented data herein were relevant to the conclusion that the low CGRP levels in SARS-CoV-2 infections might be a culprit in the ischemic process and worsening the brain arterial occlusion, thus leading to IS.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.