Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 patients reveal immune persistence up to 9 months after infection

Sandberg, John Tyler; Varnaitė, Renata; Christ, Wanda; Chen, Puran; Muvva, Jagadeeswara R.; Maleki, Kimia T.; García, Marina; Dzidic, Majda; Folkesson, Elin; Skagerberg, Magdalena; Ahlén, Gustaf; Frelin, Lars; Sällberg, Matti; Eriksson, Lars I.; Rooyackers, Olav; Sönnerborg, Anders; Buggert, Marcus; Björkström, Niklas K.; Aleman, Soo; Strålin, Kristoffer; Klingström, Jonas; Ljunggren, Hans-Gustaf; Blom, Kim; Gredmark-Russ, Sara

Background Insights into early, specific humoral and cellular responses to infection with SARS-CoV-2, as well as the persistence and magnitude of resulting immune memory is important amidst the ongoing pandemic. The combination of humoral and cellular immunity will most likely contribute to protection from reinfection or severe disease. Methods Here, we conducted a longitudinal study on hospitalized moderate and severe COVID-19 patients from the acute phase of disease into convalescence at five- and nine-months post symptom onset. Utilizing flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune memory during and after human SARS-CoV-2 infection. Findings During acute COVID-19, we observed an increase in germinal center activity, a substantial expansion of antibodysecreting cells, and the generation of SARS-CoV-2-neutralizing antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralizing antibody titers as well as robust specific memory B cell responses and polyfunctional T cell responses at five- and nine-months after symptom onset in both moderate and severe COVID-19 patients. Long-term SARS-CoV-2 specific responses were marked by preferential targeting of spike over nucleocapsid protein. Conclusions Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2 specific immunological memory in hospitalized COVID-19 patients long after recovery, likely contributing towards protection against reinfection.