Understanding the pathophysiology of typical acute respiratory distress syndrome and severe COVID-19

ABSTRACT

Introduction

Typical acute respiratory distress syndrome (ARDS) and severe coronavirus-19 (COVID-19) pneumonia share complex pathophysiology, a high mortality rate, and an unmet need for efficient therapeutics.

Areas covered

This review discusses the current advances in understanding the pathophysiologic mechanisms underlying typical ARDS and severe COVID-19 pneumonia, highlighting specific aspects of COVID-19-related acute hypoxemic respiratory failure that require attention. Two models have been proposed to describe the mechanisms of respiratory failure associated with typical ARDS and severe COVID-19 pneumonia.

Expert opinion

ARDS is defined as a syndrome rather than a distinct pathologic entity. There is great heterogeneity regarding the pathophysiologic, clinical, radiologic, and biological phenotypes in patients with ARDS, challenging clinicians, and scientists to discover new therapies. COVID-19 has been described as a cause of pulmonary ARDS and has reopened many questions regarding the pathophysiology of ARDS itself. COVID-19 lung injury involves direct viral epithelial cell damage and thrombotic and inflammatory reactions. There are some differences between ARDS and COVID-19 lung injury in aspects of aeration distribution, perfusion, and pulmonary vascular responses.

KEYWORDS:

• COVID-19
• ARDS
• pathophysiology
• respiratory failure
• perfusion

Article highlights

• • ARDS is a clinical syndrome with different causes leading to complex biological and clinical heterogeneity.

• • Although a single definition of ARDS is widely used and accepted, the heterogeneity of ARDS has been associated with negative treatment outcomes with pharmacotherapies.

• • The pathogenesis of COVID-19 lung injury involves direct viral epithelial cell damage and a host defense response with thrombotic and inflammatory reactions in the lung.

• • There are some differences between ARDS and COVID-19 lung injury in aeration distribution, perfusion, and pulmonary vascular responses.

• • Further research is warranted to identify sub-phenotypes of ARDS, including severe COVID-19 pneumonia, that could benefit from specific treatments and ventilatory strategies.

Declaration of interest

M. Bassetti reports honoraria for lectures and another educational event from Angelini, Bayer, bioMérieux, Cipla, Gilead Sciences, Menarini, Merck Sharp & Dohme (MSD), Pfizer, and Shionogi; grants from Pfizer and MSD, outside of the submitted work. Outside the submitted work, D.R. Giacobbe reports an unconditional grant from Correvio Italia, and investigator-initiated grants from Pfizer and Gilead Italia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was partly funded by the Brazilian Council for Scientific and Technological Development (CNPq), Brazilian Ministry of Science, Technology, and Innovation for Virus Network; Brasília, Brazil (no. 403485/2020-7), Funding Authority for Studies and Projects (FINEP), Brasília, Brazil (no. 01.20.0003.00), and Foundation Carlos Chagas Filho Research Support of the State of Rio de Janeiro (FAPERJ) (E-26/010.001488/2019, E-26/210.181/2020).