Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Abstract

Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11À13 of 283 days (95% CI 231À349) for anti-N and 725 days (95% CI 623À921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42À1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants.

Persistence of SARS-CoV-2-Specific Antibodies for 13 Months after Infection

“…Data on the persistence of the SARS-CoV-2-specific immune response are of great importance for managing the pandemic and planning further measures for increasing the population's resistance to the virus. To date, both sero-epidemiological and targeted cohort studies from different countries have reported detectable levels of virus-specific antibodies and duration of the protective immune response from 3 to 13 months after infection [6,7,10,12,13,17,19,21,24,25]. Previous cohort studies on the formation and persistence of SARS-CoV-2-specific humoral immune response mainly included healthcare workers as a target group having the highest risk of being exposed to SARS-CoV-2 [13,14,16,19,20,24,26,27].…”

“…A significant increase in virus-specific antibody levels is observed at days 16-35 after the onset of symptoms [4,[7][8][9][10]. Some studies have reported that antibody levels peak within the first few months, then wane and remain stable for several months, indicating that the immunity may last longer [4,8,[10][11][12][13][14][15][16]. Other studies suggest that the levels of SARS-CoV-2-specific IgG are durable and decline after 6-8 months while the number of memory B cells increases within 8 months after infection [17,18].…”

“…In contrast, another cohort study of healthcare workers in the UK showed that the seropositivity against the SARS-CoV-2 S protein remained stable in 94% (95% credibility interval [CrI] 91-96%) of participants for 6 months [14]. The most recent studies show detectable antibody responses to the SARS-CoV-2 S protein for 12-13 months [13,21].…”

Image_1.pdf

“…The longevity of serum-IgA post infection varies between different studies: seroreversion has been observed within 3 months (9,12), though other studies have shown that IgA may remain detectable over 6 months and up to a year post infection (13-18). Serum-IgA appears earlier than serum-IgG, but has been observed to be less long-lasting than serum-IgG post infection (9,12,15,19). Serum-IgG is considered the clinical standard serological assay for detection of past infection and has been shown present up to 13 months post infection (19).…”

“…Serum-IgA appears earlier than serum-IgG, but has been observed to be less long-lasting than serum-IgG post infection (9,12,15,19). Serum-IgG is considered the clinical standard serological assay for detection of past infection and has been shown present up to 13 months post infection (19). However, as the sensitivity and specificity of different IgG-assays targeting the different viral structures vary, seroconversion in commercial IgG assays may be difficult to interpret in the absence of PCR testing and in asymptomatic individuals.…”