Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals.

Etienne Brochot,Antoine Touzé,Jean Dubuisson,Gilles Duverlie,Catherine Francois,Baptiste Demey,Jean-Luc Schmit,Sandrine Belouzard,Francois Helle,Sandrine Castelain

doi:10.3389/fmicb.2020.584251

Abstract

A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.

Highlights

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently emerged and caused a human pandemic of coronavirus disease 2019 (COVID-19) (Wu et al, 2020b; Zhou et al, 2020; Zhu et al, 2020)
In order to accurately assess the time of seroconversion, we used 151 samples from 30 patients hospitalized at the Amiens University Medical Center for a COVID-19 and monitored the kinetics of detection of anti-S1, anti-S2, anti-Receptor Binding Domain (RBD) and anti-N antibodies with in-house ELISAs
With our four in-house ELISAs, we showed that the detection of the RBD and the N protein may be more suitable since it was highly or slightly more sensitive than the detection of S1 or S2, respectively

Summary

Introduction

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently emerged and caused a human pandemic of coronavirus disease 2019 (COVID-19) (Wu et al, 2020b; Zhou et al, 2020; Zhu et al, 2020). The S protein consists of two subunits, S1 which contains the Receptor Binding Domain (RBD) and S2. Commercial SARS-CoV-2 serological assays that detect antibodies specific to these viral proteins/domains have become available but they need to be finely evaluated. Neutralizing antibodies (NAbs) are considered key to recovery and protection against viral disease but the SARS-CoV-2 NAb response remains poorly documented and it is still unknown how long cured patients will be protected against new infection (Kirkcaldy et al, 2020; Ota, 2020)

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Conclusion