The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019

Sophie Stukas; Ryan L Hoiland; Jennifer Cooper; Sonny Thiara; Donald E Griesdale; Adam D Thomas; Matthew M Orde; John C English; Luke Y C Chen; Denise Foster; Anish R Mitra; Kali Romano; David D Sweet; Juan J Ronco; Hussein D Kanji; Yu-Wei R Chen; Sophia L Wong; Cheryl L Wellington; Mypinder S Sekhon

doi:10.1097/CCE.0000000000000203

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019

Crit Care Explor. 2020 Sep 17;2(9):e0203. doi: 10.1097/CCE.0000000000000203. eCollection 2020 Sep.

Authors

Sophie Stukas^{1

2}, Ryan L Hoiland^{3

4}, Jennifer Cooper^{1

2}, Sonny Thiara⁵, Donald E Griesdale^{3

5}, Adam D Thomas⁵, Matthew M Orde⁶, John C English⁶, Luke Y C Chen⁷, Denise Foster⁵, Anish R Mitra⁵, Kali Romano⁵, David D Sweet^{5

8}, Juan J Ronco⁵, Hussein D Kanji^{5

8}, Yu-Wei R Chen⁶, Sophia L Wong^{1

6}, Cheryl L Wellington^{1

2

9}, Mypinder S Sekhon⁵

Affiliations

¹ Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
² Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
³ Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
⁴ Centre for Heart, Lung, & Vascular Health, School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC, Canada.
⁵ Division of Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁶ Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
⁷ Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁸ Department of Emergency Medicine, University of British Columbia, Vancouver, BC, Canada.
⁹ International Collaboration on Repair Discoveries, School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.

Abstract

Objectives: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019.

Design: Multicenter prospective observational study.

Setting: ICU.

Patients: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group).

Interventions: Daily measurement of serum inflammatory cytokines.

Measurements and main results: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao₂/Fio₂ and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao₂/Fio₂ (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1β on the day of diagnosis.

Conclusions: The inverse relationship between serum interleukin-6 and Pao₂/Fio₂ and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-β or tumor necrosis factor-α.

Keywords: acute respiratory distress syndrome; coronavirus disease 2019; interleukin-6; respiratory failure; severe acute respiratory syndrome coronavirus 2.