Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

Abstract

A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, defining them as ‘elite neutralizers’. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in purified IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the first 10 months after mild course of COVID-19.

Seropositivity in blood donors and pregnant women during the first year of SARS‐CoV‐2 transmission in Stockholm, Sweden

“…Early research has shown that the majority of mildly infected individuals maintain detectable virus-specific B-cell responses for at least 8-10 months [17,31]. Together with the steadily increasing seropositivity observed in this study and elsewhere, such as New York City [41], these findings help allay early concerns that immunity waned in the short term, although individuals with mild infection can have antibody titres close to the assay boundary.…”

“…Several studies have highlighted the protective role antibodies play in controlling SARS-CoV-2 infection in humans [34,35] and animal models [36,37], and potent neutralizing and convergent antibodies were rapidly isolated from infected donor samples [38][39][40]. Indeed, mounting evidence suggests that most persons (>91%) previously infected with SARS-CoV-2 develop virus-specific antibodies, including following mild infections [8,16,17,31]. Critical ongoing and future research is required to determine the duration of serological responses and Bcell memory in those infected, as well as following vaccination.…”

“…We chose to survey anti-S IgG responses as these are the best indicators of past SARS-CoV-2 infection at the population level (i.e. present in >91% of PCR-positive cases) [16,17]. Spike harbours the ACE2 receptor-binding domain (RBD) and is the major target of the neutralizing antibody response, central to vaccine efforts.…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…The early anti-SARS-CoV-2 binding and neutralizing Ab response is dominated by IgM, which wanes rapidly. IgA and IgG peak subsequently, and IgG-mediated neutralizing responses are most durable and persist over months, mirrored by neutralization half-lives of a few months in serum but up to >8 months in purified IgG samples [201][202][203][204]. The persisting Ab response can be attributed to a maturing humoral immunity driven by a sustained SARS-CoV-2 antigenic stimulation in the gut of COVID-19 patients [205].…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…The early anti-SARS-CoV-2 binding and nAb response is dominated by IgM, which wanes rapidly. IgA and IgG peak subsequently, and IgG-mediated neutralizing responses are most durable and persist over months, mirrored by neutralization half-lives of a few months in serum but up to >8 months in purified IgG samples [242][243][244][245]. The persisting Ab response can be attributed to a maturing humoral immunity driven by a sustained SARS-CoV-2 antigenic stimulation in the gut of COVID-19 patients [246].…”