Modelling the association between neutralizing antibody levels and SARS-CoV-2 viral dynamics : implications to define correlates of protection against infection

BackgroundWhile anti-SARS-CoV-2 antibody kinetics have been well described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and how this impacts viral clearance. MethodsFor that purpose, we analyzed the kinetics of both viral load and neutralizing antibody levels in a prospective cohort of individuals during acute infection by Alpha variant. ResultsUsing a mathematical model, we show that the progressive increase in neutralizing antibodies leads to a shortening of the half-life of both infected cells and infectious viral particles. We estimated that the neutralizing activity reached 90% of its maximal level within 8 days after symptoms onset and could reduce the half-life of both infected cells and infectious virus by a 6-fold factor, thus playing a key role to achieve rapid viral clearance. Using this model, we conducted a simulation study to predict in a more general context the protection conferred by the existence of pre-existing neutralization, due to either vaccination or prior infection. We predicted that a neutralizing activity, as measured by ED50 >103, could reduce by 50% the risk of having viral load detectable by standard PCR assays and by 99% the risk of having viral load above the threshold of cultivable virus. ConclusionsThis threshold value for the neutralizing activity could be used to identify individuals with poor protection against disease acquisition.