Stable neutralizing-antibody levels 6 months after mild and severe COVID-19 episode

ABSTRACT

Background: One of the fundamental pillars of SARS-CoV-2 pandemic control and vaccine development is understanding mid-and long-term immunity. Early humoral response has been extensively studied, however data on what recovered individuals are still scarce and the most recent studies are based on few time points over time, which limits the comprehension of the longitudinal pattern of the potential changes. In this study we have evaluated the neutralizing activity and IgG antibody titer against SARS-CoV-2 in mild/ asymptomatic and hospitalized COVID-19 individuals, over a 6-month period. Methods: We have evaluated the kinetics of the humoral immune response in 210 individuals infected by SARS-CoV-2 covering the first and second waves of COVID-19 outbreak in Catalonia (Spain). IgG antibody titer was evaluated with an in-house sandwich ELISA against the S2 subunit, the binding domain receptor (RBD) and the nucleoprotein (NP) and the neutralizing activity was evaluated by a neutralization assay with HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. Statistical analyses were carried out using mixed-effects non-linear and linear models. Results: Most study participants developed a neutralizing humoral response against SARS-CoV-2, however the maximum neutralization titer was 10-fold lower in mild/asymptomatic individuals compared to those with a more severe illness. We observed a slow and progressive decay of neutralizing activity in individuals with mild or asymptomatic disease throughout the 6-month period. In hospitalized individuals, half maximal neutralization activity was achieved on day 10 and showed an initial rapid decline that significantly slowed and remained nearly flat after day 80. Despite this, activity at six months remained higher in hospitalized individuals compared to mild symptomatic participants. On the other hand, we observed that IgG antibody titers against S2, RBD and NP had a more marked fall without showing differences in the decay pattern between individuals with different degree of severity of the disease. Conclusion: Our data suggest that the neutralizing activity remains relatively stable for more than 6 months despite the decline in IgG antibodies, suggesting that the quality of immune response evolves and allows maintaining the neutralizing activity despite the decay in antibody titers. Our results provide a more detailed picture of the behavior of the natural humoral immune response over time that complements the current evidence on mid-term immunity.