ABSTRACT
The level and duration of protective immunity are often analyzed qualitatively or semi-quantitatively. The same strategy is applied to the analysis of antibody dynamics. At some point in time t after exposure or immunization, the presence of immunity against the infection is inferred from the level of specific antibodies by comparing it to a reference value. This approach does not account for the stochastic nature of human disease after exposure to a pathogen. At the same time, it is not fully clear what antibody level should be considered protective. The aim of this study was to develop a mathematical model for quantitative determination of protective immunity against SARS-CoV-2 and its duration. We demonstrate that the problem of describing protective immunity in quantitative terms can be broken down into 2 interrelated problems: describing the quantitative characteristics of a pathogen's virulence (in our case, the pathogen is SARS-CoV-2) and describing the dynamics of antibody titers in a biological organism. Below, we provide solutions for these problems and identify parameters of the model which describes such dynamics. Using the proposed model, we offer a theoretical solution to the problem of protective immunity and its duration. We also note that in order to quantitatively determine the studied parameters in a homogenous population group, it is necessary to know 5 parameters of the bivariate probability density function for correlated continuous random variables: the infective dose of the pathogen and the antibody titer at which the disease develops and which are still unknown.Copyright © Extreme Medicine.All right reserved.
ABSTRACT
BACKGROUND: The duration of immunity in SARS-CoV-2 infected people remains unclear. Neutralizing antibody responses are the best available correlate of protection against re-infection. Recent studies estimated that the correlate of 50% protection from re-infection was 20% of the mean convalescent neutralizing antibody titre. METHODS: We collected sera from a cohort of 124 individuals with RT-PCR confirmed SARS-CoV-2 infections from Prince of Wales Hospital, Princess Margaret Hospital, Queen Elizabeth Hospital and Queen Mary Hospitals of the Hospital Authority of Hong Kong, for periods up to 386 days after symptom onset and tested these for antibody to SARS-CoV-2 using 50% virus plaque reduction neutralization tests (PRNT50), surrogate neutralization tests and spike receptor binding domain (RBD) binding antibody. Patients were recruited from 21 January 2020 to 16 February 2021 and follow-up samples were collected until 9th March 2021. FINDINGS: Because the rate of antibody waning slows with time, we fitted lines of decay to 115 sera from 62 patients collected beyond 90 days after symptom onset and estimate that PRNT50 antibody will remain detectable for around 1,717 days after symptom onset and that levels conferring 50% protection will be maintained for around 990 days post-symptom onset, in symptomatic patients. This would potentially be affected by emerging virus variants. PRNT titres wane faster in children. There was a high level of correlation between PRNT50 antibody titers and the % of inhibition in surrogate virus neutralization tests. INTERPRETATION: The data suggest that symptomatic COVID-19 disease is followed by relatively long-lived protection from re-infection by antigenically similar viruses. FUNDING: Health and Medical Research Fund, Commissioned research on Novel Coronavirus Disease (COVID-19) (Reference Nos. COVID190126 and COVID1903003) from the Food and Health Bureau and the Theme-based Research Scheme project no. T11-712/19-N, the University Grants Committee of the Hong Kong SAR Government.