Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study

Xin Xu,Hong Zhu,Jinlin Hou,Fan Fan Hou,Jincun Zhao,Ling Li,Ailong Huang,Yanqun Wang,Quanxin Long,Jian Sun,Sheng Nie,Xiaoyong Zhang,Qinglang Zeng,Li Liu

doi:10.1038/s41392-021-00611-6

Abstract

Our understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC50 titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49–80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86–130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.

Highlights

INTRODUCTION The entry of SARSCoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[1,2,3] The spike protein is highly immunogenic and the target of many neutralizing antibodies (NAbs).[4]
We evaluated the relationship of antibody (RBD-targeting NAbs and total binding IgG) levels measured at 1:20 sample dilution with focus reduction neutralization test (FRNT) titers
RBD-based surrogate virus neutralization test (sVNT) used in this study has been demonstrated to be a robust assay for quantification of RBD-targeting NAbs

Summary

Introduction

CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[1,2,3] The spike protein is highly immunogenic and the target of many neutralizing antibodies (NAbs).[4] It has been demonstrated that convalescent blood samples obtained from individuals who recover from COVID-19 contain neutralizing activity,[5] suggesting that humans are intrinsically capable of generating antibodies that potently neutralize SARS-CoV-2. Understanding neutralizing responses, especially NAbs to RBD of SARSCoV-2, is essential in determining the onset of humoral immunity, evaluating potential capacity of viral clearance, identifying donors for convalescent plasma therapy, and assessing vaccine efficacy during clinical trials or after large-scale vaccination. Little is known about the dynamics of RBD-targeting NAbs, including its generation, longevity, and correlation with the clinical settings, at population level

Methods

Results

Conclusion