Longitudinal analysis to characterize classes and subclasses of antibody responses to recombinant receptor-binding protein (RBD) of SARS-CoV-2 in COVID-19 patients in Thailand.

Sarunporn Tandhavanant,Sirikamon Koosakunirand,Viravarn Luvira,Narisara Chantratita,Watcharapong Piyaphanee,Taniya Kaewarpai,Pornsawan Leaungwutiwong

doi:10.1371/journal.pone.0255796

Longitudinal analysis to characterize classes and subclasses of antibody responses to recombinant receptor-binding protein (RBD) of SARS-CoV-2 in COVID-19 patients in Thailand.

Sarunporn Tandhavanant, Sirikamon Koosakunirand + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0255796

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Abstract

Serological assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might contribute to confirming the suspected coronavirus disease 2019 (COVID-19) in patients not detected with molecular assays. Human antibodies that target the host angiotensin-converting enzyme 2-binding domain of the viral spike protein are a target for serodiagnosis and therapeutics. This study aimed to characterize the classes and subclasses of antibody responses to a recombinant receptor-binding protein (RBD) of SARS-CoV-2 in COVID-19 patients and investigated the reactivity of these antibodies in patients with other tropical infections and healthy individuals in Thailand. ELISAs for IgM, IgA, IgG and IgG subclasses based on RBD antigen were developed and tested with time series of 27 serum samples from 15 patients with COVID-19 and 60 samples from pre-COVID-19 outbreaks including acute dengue fever, murine typhus, influenza, leptospirosis and healthy individuals. Both RBD-specific IgA and IgG were detected in only 21% of the COVID-19 patients in the acute phase. The median IgA and IgG levels were significantly higher in the convalescent serum sample compared to the acute serum sample (P < 0.05). We observed the highest correlation between levels of IgG and IgA (rho = 0. 92). IgG1 and IgG3 were the major IgG subclasses detected in SARS-CoV-2 infection. Only acute IgG3 level was negatively associated with viral detection based on RT-PCR of ORF1ab gene (rho = -0.57). The median IgA and IgG levels in convalescence sera of COVID-19 patients were significantly higher than healthy individuals and convalescent sera of other febrile infectious patients. The analyses of antibody classes and subclasses provide insights into human immune responses against SARS-CoV-2 during natural infection and interpretation of antibody assays.

Highlights

The coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
We have developed enzyme-linked immunosorbent assay (ELISA) for IgM, IgA, IgG and IgG subclasses of antibodies against receptor-binding domain (RBD) antigen of SARS-CoV-2
Our analyses revealed that 26.67% of COVID-19 patients had detectable IgM levels while 53.33–60% had specific IgA and IgG levels during the study period. 80% of patients during the convalescent period showed increased levels of antibodies but 20% of pateints who had paired sera showed no antibody responses over time

Summary

Introduction

The coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The S1 subunit has a receptor-binding domain (RBD) that recognizes and binds to the human angiotensin-converting enzyme 2 (ACE2). The SARS-CoV-2 and severe acute respiratory syndrome coronavirus (SARS-CoV) RBD are ~73%–76% similar in genome sequence [3]. The RBD region of SARSCoV is an immunogenic antigen and can elicit neutralizing antibodies in the patients infected with these coronaviruses [4]. The receptor-binding motif (RBM), a portion of RBD making direct contacts with ACE2, is used as an antigen and an important target for antibody detection in SARS-CoV patients [5, 6]

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