Humoral Response Dynamics Following Infection with SARS-CoV-2
Authors: Grandjean Louis , Saso Anja , Torres Arturo , Lam Tanya , Hatcher James , Thistlethwayte Rosie , Harris Mark , Best Timothy , Johnson Marina , Wagstaffe Helen , Ralph Elizabeth , Mai Annabelle , Colijn Caroline , Breuer Judith , Buckland Matthew , Gilmour Kimberly , Goldblatt David ,   the Co-Stars Study Team
Published: July 2020

Introduction

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection could jeopardize the sensitivity of serological testing on which these surveys depend.

Methods

This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N), spike (S-)protein and the receptor-binding-domain (RBD) of the S-protein. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods.

Results

The mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236).

Discussion

After SARS-CoV-2 infection, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections.

Significance statement

We believe that our study has significant and urgent public health and translational impact. Firstly, our findings demonstrate that the half-life of the SARS-CoV-2 nucleoprotein antibody is only 52 days. This has immediate and important implications for large-scale seroprevalence surveys, government policy and mathematical modelling predictions which rely on serological tests that target this antibody. Secondly, the slower decay of the SARS-CoV-2 spike protein antibody identified in this study makes assays to the spike protein a more reliable target for serological assays in the longer term. We demonstrate a strong positive linear correlation between spike/RBD antibody and ACE-2 receptor binding in vitro. Our findings are therefore likely to reflect the time to loss of a functional antibody response in SARS-CoV-2.

Funding

GOSH charity, Wellcome Trust (201470/Z/16/Z and 220565/Z/20/Z). GOSH NIHR Funded Biomedical Research Centre.

Trial registration number

NCT04380896.