Cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 are lower in asymptomatic than symptomatic COVID‐19 patients

• Published in: European Journal of Immunology 2020-12, Vol.50 (12), p.2013-2024
• Main Authors: Mazzoni, Alessio, Maggi, Laura, Capone, Manuela, Spinicci, Michele, Salvati, Lorenzo, Colao, Maria Grazia, Vanni, Anna, Kiros, Seble Tekle, Mencarini, Jessica, Zammarchi, Lorenzo, Mantengoli, Elisabetta, Menicacci, Lorenzo, Caldini, Eleonora, Romagnani, Sergio, Liotta, Francesco, Morettini, Alessandro, Rossolini, Gian Maria, Bartoloni, Alessandro, Cosmi, Lorenzo, Annunziato, Francesco
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adult; Antibodies; Antibodies, Viral - immunology; Asymptomatic; Carrier State - immunology; Carrier State - virology; Cellular immunology; COVID-19; COVID-19 - immunology; Female; Humans; Immune response (humoral); Immunity, Humoral; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunological memory; Infectious diseases; Lymphocytes T; Memory cells; PD-1 protein; Programmed Cell Death 1 Receptor - immunology; Receptors, Immunologic - immunology; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes - immunology; Vaccination; Viral Proteins - immunology; Virology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202048915

The characterization of cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 is fundamental to understand COVID‐19 progression and the development of immunological memory to the virus. In this study, we detected T‐cells reactive to SARS‐CoV‐2 proteins M, S, and N, as well as serum virus‐specific IgM, IgA, IgG, in nearly all SARS‐CoV‐2 infected individuals, but not in healthy donors. Virus‐reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune‐checkpoint molecules PD1 and TIGIT. Of note, we detected antigen‐specific adaptive immune response both in asymptomatic and symptomatic SARS‐CoV‐2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell‐mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life‐threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies. COVID‐19 patients develop SARS‐CoV‐2‐specific IgA, IgM, IgG, as well as CD4+ and CD8+ T cells. Adaptive immunity is more robust in patients with a history of mild‐moderate disease than in those asymptomatic, as suggested by increased frequency and polyfunctionality of specific CD4+ T cells and higher antibody titers.