SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

Nielsen, Stine SF; Vibholm, Line K; Monrad, Ida; Olesen, Rikke; Frattari, Giacomo S; Pahus, Marie H; Højen, Jesper F; Gunst, Jesper D; Erikstrup, Christian; Holleufer, Andreas; Hartmann, Rune; Østergaard, Lars; Søgaard, Ole S; Schleimann, Mariane H; Tolstrup, Martin

BACKGROUND: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. METHODS: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3(rd) and July 9(th) 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8(+) T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls. FINDINGS: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8(+) T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2(+) individuals. INTERPRETATION: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8(+) T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity. FUNDING: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B)