Immunity to SARS-CoV-2 up to 15 months after infection

Marcotte, Harold; Piralla, Antonio; Zuo, Fanglei; Du, Likun; Cassaniti, Irene; Wan, Hui; Kumagai-Braesh, Makiko; Andréll, Juni; Percivalle, Elena; Sammartino, Josè Camilla; Wang, Yating; Vlachiotis, Stelios; Attevall, Janine; Bergami, Federica; Ferrari, Alessandro; Colaneri, Marta; Vecchia, Marco; Sambo, Margherita; Zuccaro, Valentina; Asperges, Erika; Bruno, Raffaele; Oggionni, Tiberio; Meloni, Federica; Abolhassanni, Hassan; Bertoglio, Federico; Schubert, Maren; Calzolai, Luigi; Varani, Luca; Hust, Michael; Xue, Yintong; Hammarström, Lennart; Baldanti, Fausto; Pan-Hammarström, Qiang

Background Information concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset. Methods The levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison. Findings Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months. Conclusion The data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies. Funding EU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.