Abstract

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19.Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients’ characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20–32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman’s correlation.Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147–224); median [range] years of age, 50 (20–78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman’s correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig).Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

Highlights

  • The pandemic of coronavirus disease 2019 (COVID-19) is a serious threat to global health (The Johns Hopkins Coronavirus Resource Center, 2021)

  • The decline in antibody titers shown by these studies during the relatively early phase of recovery reflects a reduction in the number of short-lived plasmablasts, which is a natural process of immune response and should not be a concern (Stephens and McElrath, 2020)

  • We studied the NT50 and the titers of antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens 6 months after the first positive results for SARS-CoV-2, to examine factors associated with NT50, and to investigate the correlation of the NT50 with the other antibody titers

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Summary

Introduction

The pandemic of coronavirus disease 2019 (COVID-19) is a serious threat to global health (The Johns Hopkins Coronavirus Resource Center, 2021). The decline in antibody titers shown by these studies during the relatively early phase of recovery reflects a reduction in the number of short-lived plasmablasts, which is a natural process of immune response and should not be a concern (Stephens and McElrath, 2020). Subsequent to this decline, long-lived plasma cells in the bone marrow play active roles in maintaining circulating neutralizing antibodies (Stephens and McElrath, 2020). Considering the lacunae of the existing studies, there is a definitive need to determine the extent of duration the neutralizing antibodies persists following natural infection

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