Strategies to DAMPen COVID-19-mediated lung and systemic inflammation and vascular injury.

Abstract

Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.

• Authors: Christian Bime, Nancy G Casanova, Janko Nikolich-Zugich, Kenneth S Knox, Sara M Camp, Joe G N Garcia
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 232 Pg. 37-48 (06 2021) ISSN: 1878-1810 [Electronic] United States
• PMID: 33358868 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Alarmins
• Cytokines
• Nicotinamide Phosphoribosyltransferase
• nicotinamide phosphoribosyltransferase, human

Topics

• Alarmins (physiology)
• Blood Coagulation Disorders (etiology)
• COVID-19 (complications)
• Capillary Permeability
• Cytokines (physiology)
• Humans
• Inflammation (etiology)
• Nicotinamide Phosphoribosyltransferase (physiology)
• Respiratory Distress Syndrome (etiology)
• SARS-CoV-2 (pathogenicity)
• Vascular System Injuries (etiology)