The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations. Author summary In this work we describe the prognostic value of early detection of SARS-CoV-2-specific T cell response in acute COVID-19, as patients without a prompt SARS-CoV-2-specific T cell response progress to severe COVID-19. We also show that the presence of specific T cells against SARS-CoV-2 when patients arrive to the emergency room is a protective factor against developing severe COVID-19, independently of the age and gender of the patient, which are two major known contributors to disease outcome. In addition, we show robust cellular and humoral immune responses persist 3 months after real-world vaccination.
【초록키워드】 COVID-19, neutralizing antibody, public health, SARS-CoV-2, immune response, vaccination, adaptive, severe COVID-19, Immunity, Prognosis, Neutralizing antibodies, antibody, T cells, SARS-COV-2 infection, severity, hospital, Infection, outcome, Clinical outcome, BNT162b2, T cell, Humoral response, cellular immunity, longitudinal study, immune responses, Early detection, Patient, Mild, humoral immune response, information, natural infection, disease, moderate, patients, T cell response, IFN-γ, mild patients, protective response, anti-SARS-CoV-2 vaccination, IL-2, recommendations, emergency room, cellular response, cellular, neutralization capacity, humoral, Predictive, Post-infection, Prognostic value, severe patients, protective factor, healthy controls, acute COVID-19, description, anti-S, uninfected, independent, Cellular and humoral responses, robust, Seven, performed, the patient, addition, analysed, characterized, provide, subjects, comparable, elicited, declined, age and gender, COVID-19 recovered patients, 【제목키워드】 vaccination, Humoral immunity, longitudinal, cellular,