Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics

Abstract

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

Keywords: COVID-19; IL-6; cytokine release syndrome; immunophenotype; severe/critical pneumonia.

Figure 1.

Timeline of disease course according to days from definitive diagnosis of illness and days from entering ICU. Before entering the ICU, 5 patients received corticosteroid therapy. In the treatment and nursing processes of the ICU, 6 patients were intubated, 2 patients were given ECMO, and 8 patients had CRS symptoms; 2 patients who had non-CRS symptoms were transferred out of the ICU. Abbreviations: CRS, cytokine release syndrome; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit.

Figure 2.

The relationship between immunologic detection and CRS after coronavirus infection. A–C, Changes in immune cell subsets and cytokine IL-6 after effective treatment in the ICU. The absolute counts of CD4⁺ and CD8⁺ cells increased, while inflammatory cytokine IL-6 decreased. Abbreviations: CRS, cytokine release syndrome; ICU, intensive care unit; IL-6, interleukin-6.

Figure 3.

The relationship between pulmonary inflammation and CRS characteristics after coronavirus infection. A and B, The relationships between the shadowed area of lung and the absolute count of CD3⁺CD8⁺ and the level of IL-6 in plasma were analyzed. In patients with a shadowed area less than 50%, the absolute counts of CD8⁺ were higher than in patients with a shadowed area ≥50%, but the level of IL-6 showed the opposite relationship. Error bars indicate the mean ± SD. P < .001 in t test. Abbreviations: CRS, cytokine release syndrome; IL-6, interleukin-6.