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

Leiqiong Gao,Lilin Ye,Zhiwei Pan,Jing Zhou,Jing Zhao,Lisha Wang,Xiangyu Chen,Zhirong Li,Guozhong Zhang,Pinghuang Liu,Yaokai Chen,Yang Yang,Ren Li,Jianfang Tang,Li Hu,Sen Yang,Qizhao Huang

doi:10.1038/s41392-021-00525-3

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.

Highlights

Our results demonstrate that compared with potent and sustained SARS-CoV-2-specific germinal center (GC) B cell responses mounted in COVID-19 patients recovered from moderate or severe symptoms, asymptomatic or mild symptomatic COVID-19 patients only induced weak and transient SARS-CoV-2-specific B cell responses
After SARS-CoV-2 antigen stimulation, we found that IFN-γ producing CD4+ and CD8+ T cells was virtually increased at early stage of hospitalization in these asymptomatic patients, which were well maintained at the middle of hospitalization and convalescent stages (Fig. 5a, b, e, f)
We further found SARS-CoV-2-specfic B cell responses were only transiently induced in early infection phase in asymptomatic or mild patients

Summary

Introduction

As of November 27, 2020, the ongoing pandemic of COVID-19, caused by SARS-CoV-2 infection, has led to over 60 million confirmed cases and over 1.4 million thousand deaths, according to WHO issued COVID-19 Weekly epidemiological update—24 November 2020—181.1 far, no vaccines has been approved to prevent SARS-CoV-2 infection, albeit several types of vaccine candidates reported at different clinical trial stages.[2,3]The SARS-CoV-2 infected patients generally manifest diverse clinical symptoms, ranging from no symptoms to critical illness, which can be further categorized into four groups, including asymptomatic, mild, moderate, and severe.[4,5,6] The adaptive immunity, encompassing humoral and cellular immune responses, is a key to clear a wide variety of viral infections, rendering patients recovered from viral diseases.[7]. As of November 27, 2020, the ongoing pandemic of COVID-19, caused by SARS-CoV-2 infection, has led to over 60 million confirmed cases and over 1.4 million thousand deaths, according to WHO issued COVID-19 Weekly epidemiological update—24 November 2020—181.1 far, no vaccines has been approved to prevent SARS-CoV-2 infection, albeit several types of vaccine candidates reported at different clinical trial stages.[2,3]. To characterize virus-specific B- and Tcell immune responses in recovered COVID-19 patients with different degrees of clinical symptoms will provide important insights into understanding the protective immunity for COVID-19, which will lay the foundation for rationally designing effective vaccines against SARS-CoV-2 infection

Methods

Results

Conclusion