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.

Robust Neutralizing Antibody Levels Detected after Either SARS-CoV-2 Vaccination or One Year after Infection

“…Reports on the longitudinal course of neutralizing antibody levels have been inconsistent, describing both losses of neutralizing capacity over time in serum samples collected from convalesced COVID-19 patients [12,22] and relative stability over months [9,23]. Many of the studies examining the neutralization capacity of sera against SARS-CoV-2 used pseudovirus particles as a surrogate to determine neutralization titers, thus avoiding the necessity of using a BSL-3 facility [10,[24][25][26]. While this approach reduces expenses and allows for higher throughput, our assay has the benefit of showing the interaction of replicating the virus with viable cells and serum components during infection.…”

Immune response (IgG) following full inoculation with BNT162b2 COVID‑19 mRNA among healthcare professionals

“…Importantly, in that study, the most prevalent adverse effects observed were pain at the injection site and flu-like symptoms, which are in accordance with the findings of the present study. Moreover, in another study that involved 203 patients who had recovered from SARS-CoV-2 infection in Denmark, broad serological profiles within the cohort were reported, with the majority of patients having robust adaptive immune responses regardless of their disease severity ( 43 ). Of note, the viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8 + T-cell responses.…”

Mild SARS-CoV-2 Illness Is Not Associated with Reinfections and Provides Persistent Spike, Nucleocapsid, and Virus-Neutralizing Antibodies

“…In addition, a small group of subjects did produce antibodies despite a history of a negative RT-PCR for SARS-CoV-2; we suspect that these subjects either had false-negative RT-PCR results, false-positive SARS-CoV-2 antibodies, or were sampled outside the window in which virus was detectable. Finally, this study only addresses the humoral response to SARS-CoV-2; subjects without evidence of humoral responses to the virus may indeed be protected through cellular or other immune mechanisms ( 22 – 24 ).…”