Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

• DOI: 10.1084/jem.20202617
• Publication Date: 2021-03-01T14:23:40Z
• Authors: Nina Le Bert; Hannah E. Clapham; Anthony T. Tan; Wan Ni Chia; Christine Y.L. Tham; Jane M. Lim; Kamini Kunasegaran; Linda Wei Lin Tan; Charles-Antoine D...; Nivedita Shankar; Joey M.E. Lim; Louisa Jin Sun; Marina Zahari; Zaw Myo Tun; Vishakha Kumar; Beng Lee Lim; Siew Hoon Lim; Adeline Chia; Yee-Joo Tan; Paul Anantharajah...; Shirin Kalimuddin; David Lye; Jenny G.H. Low; Lin-Fa Wang; Wei Yee Wan; Li Yang Hsu; Antonio Bertoletti; Clarence C. Tam
• Keywords: CD4(+) T-CELLS; Adult; Male; 0301 basic medicine; Science & Technology; SARS-CoV-2; Research & Experimental; T-Lymphocytes; Immunology; 610; COVID-19; Research & Experimental Medicine; Middle Aged; Lymphocyte Activation; Article; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Medicine; Cytokines; Humans; Life Sciences & Biomedicine; Asymptomatic Infections

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.