Extrapulmonary manifestations of severe acute respiratory syndrome coronavirus‐2 infection

Abstract

COVID‐19, the infectious disease caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has resulted in a global pandemic with unprecedented health, societal and economic impact. The disease often manifests with flu‐like symptoms and is dominated by pulmonary complications, but widely diverse clinical manifestations involving multiple organ systems can result. We posit that viral tropism and the aberrant host immune response mediate the protean findings and severity in this disease. In general, extrapulmonary manifestations are a harbinger of or contemporaneously associate with disease progression, but in the case of some extrapulmonary findings (GI and dermatologic), may track with milder disease. The precise underlying pathophysiological mechanisms remain incompletely elucidated, and additional immune phenotyping studies are warranted to reveal early correlates of disease outcomes and novel therapeutic targets. This article is protected by copyright. All rights reserved.

How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

“…The extra-pulmonary effects of SARS-CoV-2 infection [44], also supported by inflammatory events, are well justified, given that ACE2 receptors are present in tissues different from the respiratory epithelium and lung parenchyma, such as myocardium, endothelium, and intestinal mucosa [85,86]. As compared to previously identified coronaviruses, SARS-CoV-2 shows a higher invasive capacity because of the higher affinity of its spike protein to ACE2 receptors.…”

“…However, when the cytopathic effect of SARS-CoV-2 overwhelms the first line of defence, the innate immune response, alterations in signals regulating inflammatory homeostasis, release of damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs) [43]. Such events contribute, together with the viral infection, to worse outcomes via an exacerbation of the inflammatory process [44]. The involvement of neutrophils in the inflammatory mechanisms of COVID-19 has been confirmed by an increased number of circulating neutrophils that have been reported to be an indicator of the severity of respiratory symptoms and poor clinical outcomes in COVID-19 [45].…”

“…Moreover, IL-6 and IL-1β were additionally associated with fever [60]. Hugh serum levels were also detected for IL-17, G-CSF, GM-CSF, MCP1, MIP-1α in patients with severe COVID-19 [44]. Cytokine storm can lead to multi-organ failure [6,61].…”

“…In these conditions, endothelial cells would take up viral particles and produce chemo-attractants that recruit monocytes and upregulate adhesion molecules. TF activates the extrinsic coagulation pathway leading to fibrin deposition and blood clotting [44]. Accordingly, thrombosis is very frequent in COVID-19, and frequent check of coagulation parameters is recommended [14].…”

Could Naturally Occurring Coronaviral Diseases in Animals Serve as Models for COVID-19? A Review Focusing on the Bovine Model

“…HCoV OC43 [15,25] Genetically similar to bat SARS-like CoVs [26] Tropism Multiple, mainly monocytes/macrophages [11] Respiratory tract (epithelial cells and alveolar macrophages) [13,14] Mainly respiratory tract [17] Respiratory and gastrointestinal tract [10] Respiratory and gastrointestinal tract (incl. epithelial cells and alveolar macrophages) [23,24,27,28] Vaccine?…”