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Infection with the novel human coronavirus SARS-CoV-2 results in a clinical syndrome termed Coronavirus Disease 2019 (COVID-19). A proportion of patients with COVID-19 develop critical illness characterized by hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). In most respects, patients with COVID-19 ARDS resemble critically ill patients with ARDS due to other causes. Optimal management of such patients is largely in accord with established, pre-COVID ARDS protocols. Indeed, the large increase in the volume of ARDS patients because of the pandemic has afforded new evidence on the efficacy of standard practices such as lung protective ventilation, prone ventilation, and immunomodulation. However, that same large literature has also resulted in the advent of some approaches that are specific to COVID-19. Here we synthesize the evidence on the clinical presentation and management of critical COVID-19 with a focus on the impressive number of randomized, controlled trials that are now available. In so doing, we highlight what we believe to be a consensus evidence-based approach to the management of COVID-19–associated respiratory failure.



coronavirus, SARS-CoV-2, COVID-19, pandemic, critical care, acute respiratory failure, acute respiratory distress syndrome (ARDS), hypoxemia


Since the first reports of a novel viral respiratory illness emerged in December 2019 in Hubei Province, China,1 the outbreak of the novel Coronavirus SARS-CoV-2 has resulted in the infection of hundreds of millions of individuals, millions of deaths2 and an unprecedented influx of critically ill patients into intensive care units (ICU) around the world. Both professional society guidelines3 and individual approaches4–7 for the care of patients with what became known as Coronavirus Disease 2019 (COVID-19) were rapidly promulgated. These early efforts naturally preceded the reporting of new clinical and basic science data8 regarding the pathophysiology and clinical management of COVID-19 and were largely based on pre-COVID evidence for the management of sepsis and acute respiratory distress syndrome (ARDS). Subsequent work has substantially validated this early approach, while a small number of COVID specific therapies have emerged. In this review, we synthesize what is now known about COVID-19 critical illness into a consensus evidence-based approach informed by the preexisting critical care literature, emerging basic biology of coronavirus,9–11 and recently published randomized controlled trial data.12,13



In late 2019,1 a novel viral sequence was isolated from three patients presenting with a usual respiratory illness in Wuhan, China. This sequence, termed “2019-nCoV,” aligned to lineage B of the betacoronavirus (Beta-CoV) family and was highly homologous to a bat coronavirus, CoV ZXC21.9 The sequence had roughly 79% sequence identity to the previously identified severe acute respiratory syndrome (SARS) virus SARS-CoV and it was renamed “SARS-CoV-2.” The syndrome associated with SARS-CoV-2 infection became known as COVID-19.1 SAR-CoV-2 is a single ...

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