Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Wei Dai; Aifang Zhong; Qinghua Qiao; Jian Wu; Weiwei Li; Qiuyue Wu; Hongjian Zhou; Shijie Qin; Weijun Jiang; Jing Zhang; Xinyi Xia

doi:10.1186/s12985-022-01926-8

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Virol J. 2022 Nov 19;19(1):192. doi: 10.1186/s12985-022-01926-8.

Authors

Wei Dai^#^{1

2}, Aifang Zhong^#^{3

4}, Qinghua Qiao^#^{3

5}, Jian Wu^{1

6}, Weiwei Li¹, Qiuyue Wu¹, Hongjian Zhou¹, Shijie Qin¹, Weijun Jiang¹, Jing Zhang¹, Xinyi Xia^{7

8}

Affiliations

¹ Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China.
² School of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing, 210038, Jiangsu, China.
³ Department of Laboratory Medicine and Blood Transfusion, Wuhan Huoshenshan Hospital, Wuhan, 430100, Hubei, China.
⁴ Medical Technical Support Division, the 904Th Hospital, Changzhou, 213003, Jiangsu, China.
⁵ Medical and Technical Support Department, Pingdingshan Medical District, The 989Th Hospital of the PLA Joint Logistic Support Force,, Pingdingshan, 467000, Henan, China.
⁶ School of Biomedical and Informatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
⁷ Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China. xinyixia@nju.edu.cn.
⁸ Department of Laboratory Medicine and Blood Transfusion, Wuhan Huoshenshan Hospital, Wuhan, 430100, Hubei, China. xinyixia@nju.edu.cn.

^# Contributed equally.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated.

Methods: The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients.

Results: In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4⁺ T cells, CD8⁺ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21^low CD38^low B cells, effector T4 cells, and PD1⁺ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases.

Conclusion: A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

Keywords: COVID-19; IL-6; Immune cells; Lymphocyte subsets; scRNA-seq.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
COVID-19*
Humans
Interleukin-6
Leukocytes, Mononuclear
Lymphocyte Subsets
SARS-CoV-2
Severity of Illness Index

Substances

Interleukin-6