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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.
  • Nielsen SS; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
  • Vibholm LK; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Monrad I; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Olesen R; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Frattari GS; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Pahus MH; Department of Clinical Medicine, Aarhus University, Denmark.
  • Højen JF; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Gunst JD; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
  • Erikstrup C; Department of Clinical Immunology, Aarhus University Hospital, Denmark.
  • Holleufer A; Department of Molecular Biology and Genetics, Aarhus University, Denmark.
  • Hartmann R; Department of Molecular Biology and Genetics, Aarhus University, Denmark.
  • Østergaard L; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
  • Søgaard OS; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
  • Schleimann MH; Department of Infectious Diseases, Aarhus University Hospital, Denmark.
  • Tolstrup M; Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
EBioMedicine ; 68: 103410, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1252688
Preprint
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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 3rd and July 9th 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).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Country/Region as subject: Europa Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2021.103410

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Country/Region as subject: Europa Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2021.103410