Severe Acute Respiratory Syndrome-Associated Coronavirus 2 Infection and Organ Dysfunction in the ICU: Opportunities for Translational Research

Philip A Verhoef; Sujatha Kannan; Jamie L Sturgill; Elizabeth W Tucker; Peter E Morris; Andrew C Miller; Travis R Sexton; Jay L Koyner; Rana Hejal; Scott C Brakenridge; Lyle L Moldawer; Richard S Hotchkiss; Teresa M Blood; Monty B Mazer; Scott Bolesta; Sheila A Alexander; Donna Lee Armaignac; Steven L Shein; Christopher Jones; Caroline D Hoemann; Allan Doctor; Stuart H Friess; Robert I Parker; Alexandre T Rotta; Kenneth E Remy

doi:10.1097/CCE.0000000000000374

Severe Acute Respiratory Syndrome-Associated Coronavirus 2 Infection and Organ Dysfunction in the ICU: Opportunities for Translational Research

Crit Care Explor. 2021 Mar 12;3(3):e0374. doi: 10.1097/CCE.0000000000000374. eCollection 2021 Mar.

Authors

Philip A Verhoef^{1

2}, Sujatha Kannan³, Jamie L Sturgill⁴, Elizabeth W Tucker³, Peter E Morris⁴, Andrew C Miller⁵, Travis R Sexton⁶, Jay L Koyner⁷, Rana Hejal⁸, Scott C Brakenridge⁹, Lyle L Moldawer⁹, Richard S Hotchkiss^{10

11

12}, Teresa M Blood¹¹, Monty B Mazer¹¹, Scott Bolesta¹³, Sheila A Alexander¹⁴, Donna Lee Armaignac¹⁵, Steven L Shein¹⁶, Christopher Jones¹⁰, Caroline D Hoemann¹⁷, Allan Doctor¹⁸, Stuart H Friess¹⁹, Robert I Parker²⁰, Alexandre T Rotta²¹, Kenneth E Remy^{10

11

19}

Affiliations

¹ Department of Medicine, University of Hawaii-Manoa, Honolulu, HI.
² Kaiser Permanente Hawaii, Honolulu, HI.
³ Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
⁴ Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY.
⁵ Department of Emergency Medicine, Nazareth Hospital, Philadelphia, PA.
⁶ Department of Internal Medicine, The University of Kentucky-Lexington School of Medicine, The Gill Heart and Vascular Institute, Lexington, KY.
⁷ Section of Nephrology, University of Chicago, Chicago, IL.
⁸ Department of Internal Medicine, Division of Pulmonary Critical Care, Case Western School of Medicine, Cleveland, OH.
⁹ Department of Surgery, Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, FL.
¹⁰ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
¹¹ Department of Anesthesiology, Division of Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
¹² Department of Surgery, St. Louis, Washington University School of Medicine, MO.
¹³ Department of Pharmacy Practice, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA.
¹⁴ School of Nursing, The University of Pittsburgh, Pittsburgh, PA.
¹⁵ Center for Advanced Analytics, Baptist Health South Florida, Miami, FL.
¹⁶ Department of Pediatrics, Division of Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH.
¹⁷ Department of Bioengineering, George Mason University, Fairfax, VA.
¹⁸ Department of Pediatrics, Division of Critical Care Medicine, The University of Maryland School of Medicine, Baltimore, MD.
¹⁹ Department of Pediatrics, Division of Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
²⁰ Department of Pediatrics, Hematology Hematology/Oncology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY.
²¹ Department of Pediatrics, Division of Pediatric Critical Care Medicine, Duke University Medical Center, Durham, NC.

Abstract

Objectives: Since the beginning of the coronavirus disease 2019 pandemic, hundreds of thousands of patients have been treated in ICUs across the globe. The severe acute respiratory syndrome-associated coronavirus 2 virus enters cells via the angiotensin-converting enzyme 2 receptor and activates several distinct inflammatory pathways, resulting in hematologic abnormalities and dysfunction in respiratory, cardiac, gastrointestinal renal, endocrine, dermatologic, and neurologic systems. This review summarizes the current state of research in coronavirus disease 2019 pathophysiology within the context of potential organ-based disease mechanisms and opportunities for translational research.

Data sources: Investigators from the Research Section of the Society of Critical Care Medicine were selected based on expertise in specific organ systems and research focus. Data were obtained from searches conducted in Medline via the PubMed portal, Directory of Open Access Journals, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, and Web of Science from an initial search from December 2019 to October 15, 2020, with a revised search to February 3, 2021. The medRxiv, Research Square, and clinical trial registries preprint servers also were searched to limit publication bias.

Study selection: Content experts selected studies that included mechanism-based relevance to the severe acute respiratory syndrome-associated coronavirus 2 virus or coronavirus disease 2019 disease.

Data extraction: Not applicable.

Data synthesis: Not applicable.

Conclusions: Efforts to improve the care of critically ill coronavirus disease 2019 patients should be centered on understanding how severe acute respiratory syndrome-associated coronavirus 2 infection affects organ function. This review articulates specific targets for further research.

Keywords: angiotensin-converting enzyme 2 receptor; coronavirus disease 2019; critical illness; pandemic; severe acute respiratory syndrome–associated coronavirus 2.

Publication types

Review

Abstract

Publication types

Grants and funding