COVID-19: Are we dealing with a multisystem vasculopathy in disguise of a viral infection?

Abstract

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 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic with unprecedented global response. With the expanding domain of presentations in COVID-19 patients, the full range of manifestations is yet to unfold. The classical clinical symptoms for SARS-CoV-2 affected patients are dry cough, high fever, dyspnoea, lethal pneumonia whereas many patients have also been found to be associated with a few additional signs and clinical manifestations of isolated vasculopathy. Albeit a deep and profound knowledge has been gained on the clinical features and management of COVID-19, less clear association has been provided on SARS-CoV-2 mediated direct or indirect vasculopathy and its possible correlation with disease prognosis. The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices. Here we analyse the phylogenetic perspective of SARS-CoV-2 along with other strains of β-coronaviridae from a standpoint of vasculopathic derangements. Based on the existing case reports, literature and open data bases, we also analyse the differential pattern of vasculopathy related changes in COVID-19 positive patients. Besides, we debate the need of modulation in clinical approach from a hemodynamical point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV-2 affected patients.

Keywords: ACE2; Endothelium; Hemodynamics; Hypercytokinemia; SARS-CoV-2; Thrombosis; Vasculopathy.

Fig. 1

Cellular and Cytokine response of SARS-CoV-2. SARS-CoV-2 mediated cytokine storm as depicted above on binding with cells of the immune system mainly Macrophage, Dendritic cell, Monocyte. Possibility of pyroptosis cascasde shown in case of Lymphocyte

Fig. 2

Immunological response of SARS-CoV-2. SARS-CoV-2 facilitates its entry into host cell via binding of its spike glycoprotein to ACE2, Sialic acid receptor, TMPRSS2, extracellular matrix metalloproteinase inducer (CD147). Viral particle can induce activation of Alternative and Lectin pathway causing deposition of several Complement Proteins which in turn mediates severe inflammatory response. Hyperinflammatory cytokines such as IL-6, TNF, IL-17A, GM-CSF, G-CSF are found to be associated with Vascular injury. On the other hand, systemically and locally increased Angiotensin-II implicates its pathogenesis by overproduction of ROS via binding with AT1R whereas Angiotensin(1–7) counteract the activity of the Angiotensin-II by eNOS production via binding with the MasR but increased amount of Angiotensin-II affect the microvascular health by impairing eNOS mediated vasodilation