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

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.

Automated summary

Approximately 15%-20% of COVID-19-infected patients progress to severe pneumonia requiring supplemental oxygen, with 5% developing ARDS and multiorgan failure. Despite mortality rates exceeding 40%, there are still unmet needs in understanding the pathology of COVID-19-induced ARDS and developing effective therapies targeting innate immunity-driven inflammation. Some of these unmet needs include predicting hyperinflammatory viral host responses and addressing disease heterogeneity in ARDS, as well as the lack of clinically-useful biomarkers for ARDS.