Volume 31, No 11, Nov 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 11, November 2021: 1148-1162   |  Open Access

ORIGINAL ARTICLES

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects

Shanhe Yu^1,3,† , Caixia Di^2,3,† , Shijun Chen^1,† , Mingquan Guo^4,† , Jiayang Yan^2,3,† , Zhaoqin Zhu⁴ , Li Liu⁵ , Ruixue Feng¹ , Yinyin Xie¹ , Ruihong Zhang¹ , Juan Chen¹ , Mengxi Wang¹ , Dong Wei^3,6 , Hai Fang¹ , Tong Yin¹ , Jinyan Huang¹ , Saijuan Chen¹ , Hongzhou Lu^5,* , Jiang Zhu^1,3,* , Jieming Qu^2,7,*

¹Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
²Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao-Tong University, Shanghai, China
³Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China
⁴Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
⁵Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
⁶Department of Infectious Disease, Research Laboratory of Clinical Virology, Ruijin Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai, China
⁷National Research Center for Translational Medicine at Shanghai, Shanghai, China
^†These authors contributed equally: Shanhe Yu, Caixia Di, Shijun Chen, Mingquan Guo, Jiayang Yan
Correspondence: Hongzhou Lu(luhongzhou@fudan.edu.cn)Jiang Zhu(zhujiang@shsmu.edu.cn)Jieming Qu(jmqu0906@163.com)

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.

https://doi.org/10.1038/s41422-021-00562-1

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