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

Abstract

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).

Keywords: Adaptive; Antibody; Asymptomatic; CD8(+) T-cell; COVID-19; Corona; Immune response; SARS-CoV-2; Severe; Virus.