Longitudinal kinetics of RBD+ antibodies in COVID-19 recovered patients over 14 months

Eyran, Tsuf; Vaisman-Mentesh, Anna; Taussig, David; Dror, Yael; Aizik, Ligal; Kigel, Aya; Rosenstein, Shai; Bahar, Yael; Ini, Dor; Tur–Kaspa, Ran; Kournos, Tatyana; Marcoviciu, Dana; Dicker, Dror; Wine, Yariv

doi:10.1371/journal.ppat.1010569

Cited by 9 publications

(9 citation statements)

References 42 publications

(42 reference statements)

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“…This study extends our previous work showing that anti-SARS-CoV-2 spike antibodies remain detectable after 22 months past probable infection as measured with the Roche anti-S immunoassay (Perez-Saez et al, 2021). Our kinetic modeling results support previous findings indicating that antibody boost is strongest and longest lasting in vaccinees with a history of infection (Dimeglio et al, 2022a;Eyran et al, 2022;Luo et al, 2021). In contrast with previous findings, we found no significant difference in antibody boosting between age groups and slower decay rates in adults 65 years and older (Gallais et al, 2021;Vanshylla et al, 2021).…”

Section: Discussionsupporting

confidence: 91%

“…The evaluation of binding antibody levels as correlates or protection is challenged by the constant evolution of the anti-SARS-CoV-2 immune landscape through vaccination and successive epidemic waves driven by different virus variants. Longitudinal antibody studies up to 14 months follow-up have shown that antibody levels change with time since infection and/or vaccination across individuals, and depending on the immuno-assays used for detection (Eyran et al, 2022;Gallais et al, 2021;Peluso et al, 2021;Perez-Saez et al, 2021). Characterization of long-term antibody kinetics provides an opportunity for leveraging serological cohort studies to complement vaccine trials in evaluating binding antibody levels as correlate of protection against future infections.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection

Perez-Saez

Zaballa

Lamour

et al. 2022

Preprint

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Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of commercially available high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. In this work, we leverage repeated serological measurements between April 2020 and December 2021 on 1'083 participants of a population-based cohort in Geneva, Switzerland, to evaluate anti-Spike RBD antibody levels as a correlate of protection against Omicron BA.1/BA.2 infections during the December 2021-March 2022 epidemic wave. We do so by first modeling antibody dynamics in time with kinetic models. We then use these models to predict antibody trajectories into the time period where Omicron BA.1/BA.2 were the predominant circulating sub-lineages and use survival analyses to compare the hazard of having a positive SARS-CoV-2 test by antibody level, vaccination status and infection history. We find that antibody kinetics in our sample are mainly determined by infection and vaccination history, and to a lesser extent by demographics. After controlling for age and previous infections (based on anti-nucleocapsid serology), survival analyses show reveal a significant reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave with increasing antibody levels, reaching up to a three-fold reduction for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. Taken together these results indicate that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals with a history of previous SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will come next, these results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection

Perez-Saez

Zaballa

Lamour

et al. 2022

Preprint

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“…5 Facultat de Medicina, Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC), Vic, Spain. 6 Biomolecular Screening and Protein Technologies Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain. 7 Centre d' Atenció Primària (CAP) Sant Joan de Vilatorrada.…”

Section: Supplementary Informationunclassified

“…We have previously shown that 90% of those infected with SARS-CoV-2 remain seropositive 1 year after discharge [1,2]. To our knowledge, the duration of antibody responses following natural infection has not been assessed beyond 13-20 months to date [3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Sustained seropositivity up to 20.5 months after COVID-19

Dobaño

Ramírez‐Morros

Alonso

et al. 2022

BMC Med

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This study evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic. The study also assesses factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections. Despite a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period. In a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG). IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM. Antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay. Eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies. Stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020–2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination.

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“…Initial immunity after infection was assumed perfect, with all infected people transiting to an immune state upon recovery from infection. The duration of immune protection varied according to vaccination status, as well as prior infection status among vaccinated individuals (11, 18, 19). Anti-spike antibody titres have been demonstrated to be a consistent correlate of protection against SARS-CoV-2 infection (20).…”

Section: Methodsmentioning

confidence: 99%

Impact of Immune Evasion, Waning and Boosting on Dynamics of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority

Fisman

Amoako

Simmons

et al. 2023

Preprint

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Background: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. Methods: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, hybrid effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. Results: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3-4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of hybrid immunity, frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. Interpretation: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.

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Longitudinal kinetics of RBD+ antibodies in COVID-19 recovered patients over 14 months

Cited by 9 publications

References 42 publications

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection

Sustained seropositivity up to 20.5 months after COVID-19

Impact of Immune Evasion, Waning and Boosting on Dynamics of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority

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