key: cord-0971387-dp3j3hry
authors: Choe, Pyoeng Gyun; Kim, Kye-Hyung; Kang, Chang Kyung; Suh, Hyeon Jeong; Kang, EunKyo; Lee, Sun Young; Kim, Nam Joong; Yi, Jongyoun; Park, Wan Beom; Oh, Myoung-don
title: Antibody Responses One Year after Mild SARS-CoV-2 Infection
date: 2021-05-21
journal: J Korean Med Sci
DOI: 10.3346/jkms.2021.36.e157
sha: 43e0f454fb710f681e436d0503e019c9d4519154
doc_id: 971387
cord_uid: dp3j3hry

Understanding the long-term kinetics of antibodies in coronavirus disease 2019 (COVID-19) is essential in interpreting serosurvey data. We investigated the antibody response one year after infection in 52 mildly symptomatic patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, using three commercial immunoassays and a surrogate virus neutralization test (sVNT) kit. Anti-N pan-immunoglobulin (Ig), anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the antibody could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients.

EunKyo Kang https://orcid.org/0000-0001-5844-5625 Sun Young Lee https://orcid.org/0000-0002-1626-2721 Nam Joong Kim https://orcid.org/0000-0001-6793-9467 Jongyoun Yi https://orcid.org/0000-0001-9098-3765 Wan Beom Park https://orcid.org/0000-0003-0022-9625 Myoung-don Oh https://orcid.org/0000-0002-2344-7695

Funding Funding for this project was supported by the research fund of Seoul National University Hospital (Grant No. 04-2021-0010). The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The authors have no potential conflicts of interest to disclose. [Ig] electrochemiluminescence immunoassay (ECLIA), Roche Diagnostics, https:// diagnostics.roche.com), anti-S IgG enzyme-linked immunosorbent assay (anti-S IgG ELISA, InBios International, https://www.inbios.com), and anti-S subunit 1 IgG ELISA (anti-S1 IgG ELISA, Euroimmun, https://www.euroimmune.com). A surrogate virus neutralization test (sVNT, GenScript, https://www.genscript.com) was used to evaluate neutralizing activity targeting the spike receptor-binding domain. These four assays have received Food and Drug Administration Emergency Use Authorizations.

Data from 52 patients with mildly symptomatic COVID-19 were analyzed ( Table 1) . Sixteen (30.8%) were male with a median age of 26 years (interquartile range [IQR], 22-39.5). The median interval from symptom onset to sampling was 351 days (IQR, 349-352 days). None of the patients reported exposure to other COVID-19 patients or developing symptoms of COVID-19 after recovery. One year after infection, anti-N pan-Ig, anti-S IgG, and anti-S1 IgG were detected in 43 (82.7%), 44 (84.6%), and 30 (57.7%), respectively. In 49 (94.2%), the SARS-CoV-2 antibodies could be detected by either anti-N pan-Ig or anti-S IgG assay. In the sVNT, 30 (57.7%) had positive neutralizing activity. Twenty-seven patients (51.9%) showed positive results in all three binding antibody assays and sVNT.

Understanding the longevity of humoral immunity to SARS-CoV-2 is essential for predicting herd immunity to SARS-CoV-2 and interpreting serosurvey data. In case of SARS-CoV-1, 90% and 50% of patients have been shown to maintain IgG antibodies for two and three years, respectively. 4 Studies conducted in the early COVID-19 epidemic showed that the antibody titers of the patients with mild COVID-19 declined more quickly than those reported Anti-N = anti-nucleocapsid, pan-Ig = pan-immunoglobulin, ECLIA = electrochemiluminescence immunoassay, Anti-S = anti-spike, ELISA = enzyme-linked immunosorbent assay, anti-S1 = anti-spike subunit: sVNT = surrogate virus neutralization test. a Underlying disease: hypertension (1), diabetes (1), and bronchitis (1) were included.

for SARS-CoV-1, 5 and waning immunity has been confirmed five months after infection. 6 Therefore, concerns about the usefulness of population-based seroprevalence studies have been raised because rapid waning immunity may lead to substantial false negatives in an immunoassay and underestimate the number of persons with previous SARS-CoV-2 infection. 7

Recent studies showed antibodies against SARS-CoV-2 remained stable over time, declining moderately over 6-8 months after infection. 3, 8 In the present study, we showed that the antibody-positive rate was still high one year after infection in two of three commercial kits (82.7-84.6%), even in mildly symptomatic patients. By combining the anti-N pan-Ig and anti-S IgG assay results, we could identify ~94% of patients with mildly symptomatic SARS-CoV-2 infection one year after symptom onset.

Longitudinal seroprevalence study of healthcare workers in the United Kingdom showed that SARS-CoV-2 anti-N antibodies waned faster, but anti-S IgG remained stably detected, 9 and other study showed that anti-N antibodies frequently became undetectable by 5-7 months. 10 However, the present study demonstrated that despite the possible waning of anti-N antibodies, the anti-N pan-Ig assay could be useful to estimate immunity or seroprevalence up to one year after infection. It is of note that anti-N antibodies are useful to differentiate vaccination-induced immunity from that conferred by natural infection, because most vaccines except live attenuated or inactivated vaccines have been developed targeting the spike protein.

Our study has several limitations. First, the relatively small sample size and the predominantly young population reduce the generalization of the results. Second, due to the cross-sectional study design, we could not get the baseline or longitudinal serological samples, although of 52 patients, 44 patients also participated in an 8-month cross-sectional survey previously reported. 3 There was no significant difference between 8 and 12 months after infection in positivity to anti-N pan-Ig, anti-S IgG, and sVNT activity, except anti-S1 IgG (Supplementary Table 1 ).

In conclusion, despite waning immunity, SARS-CoV-2 antibodies can be detected up to one year after infection, even in mild COVID-19 patients. Especially, anti-N pan-Ig assay or its combination with anti-S IgG assay could be used to detect past SARS-CoV-2 infection at least one year after infection even in a vaccinated population.

The Institutional Review Boards (IRB) of Seoul National University Hospital and Pusan National University Hospital approved the study (IRB No. H-2009-168-1160 and 2010-013-096). Written informed consent was obtained from all patients.

Selecting coronavirus disease 2019 patients with negligible risk of progression: early experience from non-hospital isolation facility in Korea

Antibody responses to SARS-CoV-2 at 8 weeks postinfection in asymptomatic patients

Antibody responses 8 months after asymptomatic or mild SARS-CoV-2 infection

Duration of antibody responses after severe acute respiratory syndrome

Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19

Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection

Decline in SARS-CoV-2 antibodies after mild infection among frontline health care personnel in a multistate hospital network -12 states

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers

Orthogonal SARS-CoV-2 serological assays enable surveillance of low-prevalence communities and reveal durable humoral immunity

 Supplementary Table 1 Comparison of antibody positivity between 8 and 12 months after mild SARS-CoV-2 infection (n = 44) Click here to view