Immune Characteristics Predict Outcome of Severe and Critical COVID-19 Patients

Abstract

Background: Recently, the novel coronavirus (COVID-19) has broken out worldwide, with rapid increase of infected patients in severe and critical conditions. Immune patterns are considered to be closely associated with disease progression of patients. This study is aimed to evaluate the correlation between immune characteristics and clinical parameters in severe and critical COVID-19 patients. Methods: Thirty-six severe and critical types of adult cases with COVID-19 were enrolled from February to March, 2020, and 36 healthy donors were used as control. We detected lymphocyte subpopulations and levels of cytokines in peripheral blood of these patients by using flow cytometer. The basic information, disease outcome, computed tomography imaging, (1,3)-β-D-glucan detection (G test), microbiota infection, coagulation profile (eg, D-Dimer), and serum biochemical test evaluated liver, renal and heart function, including aspartate aminotransferase, g-glutamyl trans peptidase, urea, creatine kinase, lactate dehydrogenase of all these patients were also collected. Findings: We found that cell numbers in these patients were obviously decreased compared to control, including total lymphocytes, total T, CD4+ T, CD8+ T, B and NK cells, particularly in T cells. CD4+/CD8+ T cell ratio in these COVID-19 patients was significantly increased. The cytokine levels, including IL-2, IL-4, IL-6, IL-10, TNF-a and IFN-g, were remarkably increased; especially IL-6 and IL-10 were more elevated. Moreover, patients with high lymphocyte level, excluded B cells, and with low IL-6 or IL-10 level had a good survival. The percentage of patients with high level of lymphocytes was markedly higher in live patients than that in died patients, but an opposite result for B cells; patients with low level of IL-6 and IL-10 were basically live. Meanwhile, patients with low level of lymphocytes were easy to infect with microbiota. Lastly, IL-6 or IL-10 level was closely correlated with D-Dimer and organ dysfunction biomarkers. Interpretation: Collectively, severe and critical COVID-19 patients exhibit lymphopenia and high level of cytokines, especially impaired T cells, and increased IL-6 or IL-10, which are served as potential biomarkers for disease progression. Therefore, improving lymphopenia and targeting cytokines should be the effective therapeutic strategies for severe and critical COVID-19 patients. Funding Statement:This work was supported by grants from the Emergency Prevention and Control of COVID-19 Project of Henan Province (No. 201100310900), the National Natural Science Foundation of China (No. 91942314, U1804281, 81602024), Funding from State's Key Project of Research and Development Plan (No. 2018YFC1313400, 2016YFC1303500). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the institutional review board at the First Affiliated Hospital of Zhengzhou University.