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The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

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Title: The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity
Authors: Leiqiong Gao, Jing Zhou, Sen Yang, Lisha Wang, Xiangyu Chen, Yang Yang, Ren Li, Zhiwei Pan, Jing Zhao, Zhirong Li, Qizhao Huang, Jianfang Tang, Li Hu, Pinghuang Liu, Guozhong Zhang, Yaokai Chen, Lilin Ye
Source: Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-10 (2021)
Publisher Information: Nature Publishing Group, 2021.
Publication Year: 2021
Collection: LCC:Medicine
LCC:Biology (General)
Subject Terms: Medicine, Biology (General), QH301-705.5
More Details: Abstract The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2059-3635
Relation: https://doaj.org/toc/2059-3635
DOI: 10.1038/s41392-021-00525-3
Access URL: https://doaj.org/article/2bcca2cbe28a4ebeb831552c3efb9f24
Accession Number: edsdoj.2bcca2cbe28a4ebeb831552c3efb9f24
Database: Directory of Open Access Journals
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  Data: <searchLink fieldCode="AR" term="%22Leiqiong+Gao%22">Leiqiong Gao</searchLink><br /><searchLink fieldCode="AR" term="%22Jing+Zhou%22">Jing Zhou</searchLink><br /><searchLink fieldCode="AR" term="%22Sen+Yang%22">Sen Yang</searchLink><br /><searchLink fieldCode="AR" term="%22Lisha+Wang%22">Lisha Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Xiangyu+Chen%22">Xiangyu Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Yang+Yang%22">Yang Yang</searchLink><br /><searchLink fieldCode="AR" term="%22Ren+Li%22">Ren Li</searchLink><br /><searchLink fieldCode="AR" term="%22Zhiwei+Pan%22">Zhiwei Pan</searchLink><br /><searchLink fieldCode="AR" term="%22Jing+Zhao%22">Jing Zhao</searchLink><br /><searchLink fieldCode="AR" term="%22Zhirong+Li%22">Zhirong Li</searchLink><br /><searchLink fieldCode="AR" term="%22Qizhao+Huang%22">Qizhao Huang</searchLink><br /><searchLink fieldCode="AR" term="%22Jianfang+Tang%22">Jianfang Tang</searchLink><br /><searchLink fieldCode="AR" term="%22Li+Hu%22">Li Hu</searchLink><br /><searchLink fieldCode="AR" term="%22Pinghuang+Liu%22">Pinghuang Liu</searchLink><br /><searchLink fieldCode="AR" term="%22Guozhong+Zhang%22">Guozhong Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Yaokai+Chen%22">Yaokai Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Lilin+Ye%22">Lilin Ye</searchLink>
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  Data: Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-10 (2021)
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  Data: Abstract The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.
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