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

Vanshylla, Kanika; Di Cristanziano, Veronica; Kleipass, Franziska; Dewald, Felix; Schommers, Philipp; Gieselmann, Lutz; Gruell, Henning; Schlotz, Maike; Ercanoglu, Meryem S; Stumpf, Ricarda; Mayer, Petra; Heger, Eva; Johannis, Wibke; Horn, Carola; Suárez, Isabelle; Jung, Norma; Salomon, Susanne; Eberhardt, Kirsten Alexandra; Fätkenheuer, Gerd; Pfeifer, Nico; Eggeling, Ralf; Augustin, Max; Lehmann, Clara; Klein, Florian

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.