Persistence of neutralizing antibodies a year after SARS-CoV-2 infection

Introduction

Infection with Severe acute respiratory coronavirus 2 (SARS-CoV-2) induces antibodies in most subjects to viral nucleoprotein (N) and spike glycoprotein (S) (1). Neutralizing antibodies (NAb) against SARS-CoV-2 target the receptor-binding domain (RBD) of the spike protein and sterically interfere with the binding of the viral spike protein and the host’s angiotensin-converting enzyme 2 (ACE2) (2, 3). NAb levels are highly predictive of protection against infection and clinical disease (4) and detectable NAb have been reported to persist in most subjects at least six to twelve months after infection (5–12).

SARS-CoV-2 virus is constantly mutating yet most changes have little or no impact on its virulence (13). However, some changes are causing concerns regarding disease severity, viral transmissibility and potential escape from natural and vaccine-induced immunity (14). The World Health organization (WHO) in collaboration with international network of experts has characterized Variants of Interest (VOI) and Variants of Concern (VOC) (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/). Reduced NAb levels as compared to the wild-type virus have been shown against VOCs, especially against Beta variant, both after vaccination (12, 15–17) and nine (12) and twelve months (11) after infection. Similar reduction in NAb titers has also been reported against Delta variant from convalescent sera collected three to twelve months post symptoms or after vaccination (18, 19).

Previous infection with SARS-CoV-2 has shown to induce effective immunity and protection against reinfections in most individuals (20, 21). In animal studies, a protective antibody titer against SARS-CoV-2 infection has been suggested to be low (22, 23). Higher IgG antibody levels against SARS-CoV-2 among health care workers within three months after vaccination were found to be associated with lower infectivity (24). However, a protective threshold for humans is still under debate and subject to standardization of serological methods. The accumulating research data on the persistence of antibodies after natural infection, and neutralizing antibodies in particular, will provide important insight into estimating for how long antibodies induced by COVID-19 vaccination can be expected to persist and provide protection against emerging SARS-CoV-2 variants. In this study, we investigated the antibody persistence up to 14 months after natural SARS-CoV-2 infection and assessed the potential cross-protection by comparing the NAb levels of wild-type virus (B.1 lineage) to three VOC strains Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2).

Results

Study cohort characteristics

We invited a total of 2586 subjects who had experienced a PCR-confirmed SARS-CoV-2 infection six months earlier (between February 29^th and April 30^th 2020) to participate in the study. A total of 1292 (50%) participated and the median time from diagnosis to sampling was 7.6 months (range 5.9 to 9.9 months). The median age of the participants at the time of diagnosis was 50.0 years (range 17.3 to 94.3 years) and 40% were male. The majority of the participants had experienced a mild disease and 15% had been hospitalized because of COVID-19. By May 21^st 2021, up to 77% (995/1292) of those who participated at six months returned for a twelve month follow-up visit with a median time from diagnosis to sampling being 12.7 months (range 11.7 to 14.3 months) (Figure 1). Participant demographics and clinical characteristics are presented in Table 1.

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Figure 1.

Study flow chart

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Table 1.

Demographics and clinical characteristics of study participants in the study cohorts at six and twelve months after infection.

Persistence and kinetics of SARS-CoV-2 antibodies

We first assessed the persistence of NAb and serum IgG antibodies specific to SARS-CoV-2 full-length spike protein (SFL-IgG), receptor binding domain of spike protein (RBD-IgG) and nucleoprotein (N-IgG) at six months following SARS-CoV-2 infection. We found that 89% (1148/1292) of the subjects had NAb against the wild-type virus, 96% (1240/1292) had antibodies to SFL and RBD (S-IgG) and 66% (846/1292) had N-IgG. We randomly selected to further analysis 400 subjects of the 652 subjects who had not received a SARS-CoV-2 vaccination of the 995 subjects who participated at both time points. Of the 400 subjects 33 were later excluded from the analysis due to rise in antibody levels between six and twelve month sampling (n=29), late registration of vaccination records (n=2) or overlapping six and twelve month sampling (n=2). Therefore, the subset from which we further assessed the persistence of neutralizing and IgG antibodies a year after SARS-CoV-2 infection consisted of 367 subjects. Participant demographics and clinical characteristics for the selected cohort were similar to the overall cohort and are shown in Table 1. NAb, S-IgG and N-IgG antibodies were detected in 91%, 98% and 67% of subjects in the selected cohort at six months after infection, respectively (Table 2). One year after infection the proportion of positive samples was still high READ MORE>>>>>Persistence of neutralizing antibodies a year after SARS-CoV-2 infection

Originally Published Medrxiv.org