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Review: Evidence-Based Management of the Critically Ill Adult with COVID-19

Key findings

  • A recent review by Massachusetts General Hospital physicians provides a treatment algorithm and detailed guidance about triage, management of respiratory failure and general ICU care for critically ill adults with COVID-19
  • CT should not be used for initial diagnosis but is appropriate where alternate diagnoses need to be evaluated or to identify high-risk patients with a negative polymerase chain reaction test who could benefit from further work-up
  • Acute hypoxemic respiratory failure in COVID-19 patients is now well established to represent a form of acute respiratory distress syndrome and should be managed as such
  • The lifecycle of the SARS-CoV-2 virus and its effects on the host immune system suggest possible targets for therapy, and several therapies have received emergency use authorization for hospitalized adults with COVID-19

A wealth of clinical and basic science information about managing severely and critically ill patients with COVID-19 has become available in the past few months. In the Journal of Intensive Care Medicine, Massachusetts General Hospital physicians synthesize information from the pre-existing critical care literature with emerging data from observational reports and randomized controlled trials.

Raghu R. Chivukula, MD, PhDKathryn Hibbert, MD, and C. Corey Hardin, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Mass General, Jason H. Maley, MD, a clinician and research fellow in the Department of Medicine, and David M. Dudzinski, MD, of the Cardiac Intensive Care Unit, provide a treatment algorithm and detailed guidance about triage, management of respiratory failure and general ICU care for critically ill adults with COVID-19. This summary addresses some current and former controversies related to treatment.

Clinical Features

Early anecdotal reports claimed COVID-19 presents with a novel phenotype characterized by preserved compliance in the face of severely impaired oxygenation. Some went further to propose that COVID-19 respiratory failure represents a state analogous to high-altitude pulmonary edema (HAPE).

These claims have been conclusively refuted by multiple comprehensive analyses demonstrating that gas exchange and pulmonary mechanics in COVID-19 are entirely in line with published series on acute respiratory distress syndrome (ARDS) in the pre–COVID-19 era and are inconsistent with HAPE. Hypoxemic respiratory failure caused by COVID-19 is a form of ARDS and should be managed as such. The keys are lung-protective low-tidal volume ventilation, avoidance of barotrauma, a conservative fluid strategy and prone ventilation, with the use of inhaled pulmonary vasodilators, neuromuscular blockade and extracorporeal membrane oxygenation (ECMO) when necessary.

A second controversy is the possibility of a pathologically hyperinflammatory state in severe COVID-19 known as a "cytokine storm." Similar pathophysiology has been proposed for SARS and influenza. However, it is far from clear whether immune activation in COVID-19 causes disease progression or instead identifies critically ill patients with a robust and possibly appropriate immune response.


In light of doubts about the "cytokine storm," it remains unclear whether hyperinflammation is a rational therapeutic target for COVID-19. Baricitinib, an oral JAK inhibitor, has received emergency use authorization (EUA) for use in combination with remdesivir to treat COVID-19 in hospitalized adults who require supplemental oxygen, invasive mechanical ventilation or ECMO.

Corticosteroid therapy is now considered the standard of care in hospitalized COVID-19 patients on supplemental oxygen, mechanical ventilation or ECMO. This recommendation is based on 28-day mortality data on dexamethasone published in The New England Journal of Medicine. Long-term effects on mortality remain to be seen.

Statin use has been advocated because patients with pre-existing cardiovascular disease appear to be at high risk for severe COVID-19 and death, and many are likely to meet existing guideline-lined indications for statin therapy as primary or secondary prevention. A second argument, much more speculative, is that statins modulate the innate immune system. In light of the risks of transaminitis and rhabdomyolysis, the authors do not recommend statin use in COVID-19 patients except when there is an evidence-based primary indication.

Antiviral Therapies

  • Remdesivir has received EUA for hospitalized patients with COVID-19. As of November 22, the Infectious Diseases Society of America suggests five days of therapy for patients on supplemental oxygen alone and 10 days for those on mechanical ventilation or ECMO
  • Antibodies that block viral engagement with ACE2, the cell surface receptor, are in clinical trials. The combination of casirivimab and imdevimab, which recently received EUA, is indicated only for certain cases of mild to moderate COVID-19, not for patients hospitalized with COVID-19
  • The FDA has revoked its EUA for chloroquine and hydroxychloroquine because of these drugs' ineffectiveness in treating COVID-19 and the risk of serious adverse events
  • Convalescent plasma received EUA in August 2020. As of October 9, the National Institutes of Health says there are insufficient data to recommend either for or against the use of convalescent plasma to treat COVID-19

Clinicians should note that as targeted therapies become more available, obtaining a definitive diagnosis of COVID-19 could change management.

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Related topics


Since the initial outbreak of COVID-19, clinicians have treated hundreds of thousands of patients. At the same time, over 55,000 COVID-related research articles have been published (albeit of heterogeneous quality). There is now substantial consensus on optimal treatment of the critically ill patient with COVID-19.


By reviewing autopsy and biopsy studies, Massachusetts General Hospital researchers have shown that COVID-19 manifests principally as diffuse alveolar damage, the histopathologic pattern typically associated with acute respiratory distress syndrome.