A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients.

Yuxin Chen,Rui Huang,Yang Li,Yong Liu,Xin Tong,Han Shen,Chao Wu,Bin Gu,Jiawei Yan,Ron A M Fouchier

doi:10.1371/journal.ppat.1008796

Yuxin Chen, Rui Huang + Show 8 more

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https://doi.org/10.1371/journal.ppat.1008796

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Abstract

There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19.

Highlights

The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in China, has rapidly spread worldwide
The world is facing an unprecedented challenge with communities and economies affected by the growing pandemic of coronavirus disease 2019 (COVID-19)
Our results indicated that most patients generated humoral responses against nucleoprotein and three spike proteinrelated antigens with their distinct kinetics profiles

Summary

Introduction

The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in China, has rapidly spread worldwide. We demonstrated that early, arising antibody responses were detected concurrent with positive viral RNA among severe patients, while antibody responses which often facilitate the viral clearance were observed from non-severe patients. This prompted us to further explore the antigen specificity and humoral responses among severe and non-severe patients. Recent studies demonstrated that transfusion of convalescent plasma containing the neutralizing antibodies resulted in clinical improvement [6, 7], which necessitates a comprehensive understanding of the specificity, isotypes, Humoral responses in severe and non-severe COVID-19 patients potency and persistence of the neutralizing antibody components present in the convalescent sera of clinically recovered COVID-19 patients

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