Research Priorities for Coronavirus Disease 2019 in Critical Illness

The Surviving Sepsis Campaign

Craig M. Coopersmith, MD, MCCM; Massimo Antonelli, MD; Seth R. Bauer, PharmD, FCCM; Clifford S. Deutschman, MS, MD, MCCM; Laura E. Evans, MD, MSc, FCCM; Ricard Ferrer, MD, PhD; Judith Hellman, MD; Sameer Jog, MD; Jozef Kesecioglu, MD, PhD; Niranjan Kissoon, MB BS, MCCM; Ignacio Martin-Loeches, MD, PhD; Mark E. Nunnally, MD, FCCM; Hallie C. Prescott, MD, MSc; Andrew Rhodes, MB BS, MD(Res); Daniel Talmor, MD, MPH; Pierre Tissieres, MD, DSc; Daniel De Backer, MD, PhD


Crit Care Med. 2021;49(4):598-622. 

In This Article

Abstract and Introduction


Objectives: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients.

Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document.

Methods: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research.

Results: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given?

Conclusions: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.


Since the first reported cases of coronavirus disease 2019 (COVID-19) in December 2019, millions of people worldwide have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.[1] The majority of patients infected are either asymptomatic or mildly symptomatic. However, a minority of infected patients will go on to be hospitalized, and, of these, a significant proportion will be admitted to the ICU. Mortality estimates vary widely in critically ill patients with COVID-19 with recent reports demonstrating improved outcomes during the course of the pandemic,[2,3]

Due to the worldwide devastation caused by the COVID-19 pandemic, there has been an exponential increase in knowledge related to the disease. The quality of the available information related to COVID-19 varies wildly. High-quality rigorous clinical trials and scientific discoveries have gone through peer review and have fundamentally changed both bedside management and understanding of the disease. Simultaneously, immeasurable anecdotal information has been promulgated, both within the medical literature and the lay press. Much of this has not been subjected to peer review or has led to adoption of clinical strategies at the bedside in a manner that is unique to this global challenge. In addition, both prevention of and management of COVID-19 have become politicized in many countries in ways not seen with other diseases, contributing to challenges faced by both the lay public and the medical community. Balancing the needs for rapid knowledge advances and dissemination with fidelity to the scientific method has, at times, proved to be challenging during the pandemic where new discoveries are heralded nearly every week, and "gamechanger" therapies may turn out not to be beneficial or even harmful.

Within this context, numerous guidelines have been published related to the management of COVID-19.[4–7] These guidelines reflect the best available evidence toward understanding SARS-CoV-2 infection and the management of COVID-19. At the same time, they indirectly highlight numerous gaps related to current understanding of a disease which is still very new and is responsible for the worst global pandemic in over a century. In light of the numerous challenges that currently exist, the possibilities for research into COVID-19 are nearly limitless. The goal of this document is for the Surviving Sepsis Campaign to narrow these possibilities down to a small group of research priorities that, if addressed, would lead to improved understanding and outcomes for critical illness caused by COVID-19.