The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis
Authors: Wenjun Wang , Xiaoqing Liu , Sipei Wu , Puyi Lie , Liyan Huang , Yimin Li , Linling Cheng , Sibei Chen , Lingbo Nong , Yongping Lin , Jianxing He 
Published: February 2020

IMPORTANCECOVID-19-infected pneumonia patients with severe immune abnormalities and risk of cytokine release syndrome. The definition, prevention, and treatment of COVID-19-infected pneumonia in critically ill patients with cytokine release syndrome symptoms is an important problem.OBJECTIVETo define the cytokine release syndrome-like (CRSL) in COVID-19-infected pneumonia in critically ill patients and study the risk factors and therapeutic strategies.DESIGN, SETTING, AND PARTICIPANTSThis is a retrospective, single center case study of 11 COVID-19-infected pneumonia patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The follow-up termination date was February 19, 2020.EXPOSERESEleven COVID-19-infected pneumonia patients with ARDS in the ICU. Some of these patients also had cytokine release syndrome-like (CRSL). Immunologic detection, clinical characteristics, and clinical treatment analysis were carried out to define the CRSL in these COVID-19-infected pneumonia patients.MAIN OUTCOMES AND MEASURESClinical, radiological, immunology (including immune cell subsets and cytokines analysis), laboratory, and clinical treatment data were collected and analyzed. The critically ill patients with CRSL were defined. Prevention and control strategies were studied.RESULTSOf 11 critically ill patients in the ICU, the median age was 58 (Inter-Quartile Range{IQR}, 49–72; range, 26–72 years), and 10 (83.3%) were males. Ten (83.3%) patients had extensive pulmonary inflammation and ARDS (the median time from the first symptom to ARDS was 10.0 d), fever, and hypoxia; four (28.6%) patients experienced shock. The lymphocyte subpopulations including CD3 (CD3 + CD45+), CD4 (CD3 + CD4+), CD8 (CD3 + CD8+), NK (CD3-CD16 + CD56 +), Tregs (CD4 + CD25 + CD127 low), B lymphocyte (CD3-CD19 +) cells; and cytokines including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ were detected at different time points. All of the patients had a decrease of CD3 (IQR,169–335; range, 50–635 cells/μL), CD4 (IQR,101–303; range, 27–350 cells/μL), CD8 (IQR, 33–141; range, 21–277 cells/μL); ten (90.9%) patients have a decrease in NK immune cells (IQR,8–72; range, 5–170 cells/μL); both of Tregs (IQR,3.3-7.8;rang,2.3-9.4%) and B immune cells (IQR,61-146; rang,44-222 cells/μL)were decreased in two (18.2%) patients. And nine patients were increase in CD4 / CD8 (IQR,3.3–7.8%; range, 2.3–9.7%). All patients had a significant increase of IL-6 (IQR,14.26-92.2; range, 4.58–1182.91ng/L). Eight (72.7%) patients were determined to have CRSL characteristics, including pulmonary inflammation, fever, a decrease of CD4, CD8, and NK cells; an increase of CD4/CD8, a significant increase of IL-6, and the dysfunction of non-pulmonary organs. The numbers of CD4, CD8, and NK cells and the level of IL-6 in peripheral blood were correlated with the area of pulmonary inflammation in CT images (P<0.05). Mechanical-ventilation used to increase blood oxygen concentration could increased the numbers of CD4 (after Vs before ventilation=259±53 VS 507±101; P=0.013, and CD8 (after Vs before ventilation=193±38 VS 279±63; P=0.048), while decreasing the level of IL-6 (after Vs before ventilation=223.2± 89.9 VS 26.8±10; P=0.041). The increased of IL-6 was occurred earlier than the decrease of CD4·, CD8 in the patients with rapidly worsened after ICU.CONCLUSIONS AND RELEVANCEIn this retrospective analysis of 11 critically ill pneumonia patients infected with COVID-19, we defined and identified eight patients (72.7%) with cytokine release syndrome-like (CRSL). We found that a large area of lung injury (≥50%) with an decrease of CD4, CD8 (Lower than 50% minimum normal range) and increase of IL-6 in peripheral blood was the highest risk factor of CRSL. IL-6 was a early indicators of CRSL in COVID-19-infected pneumonia. We also found that reduce injury to the lung is a useful method to prevent and improve COVID-19-infected pneumonia-related CRSL in critically ill pneumonia patients.