Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5

Maren Bormann; Leonie Brochhagen; Mira Alt; Mona Otte; Laura Thümmler; Lukas van de Sand; Ivana Kraiselburd; Alexander Thomas; Jule Gosch; Peer Braß; Sandra Ciesek; Marek Widera; Sebastian Dolff; Ulf Dittmer; Oliver Witzke; Folker Meyer; Monika Lindemann; Andreas Schönfeld; Hana Rohn; Adalbert Krawczyk

doi:10.3389/fimmu.2023.1150667

Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5

Front Immunol. 2023 Jul 13:14:1150667. doi: 10.3389/fimmu.2023.1150667. eCollection 2023.

Authors

Maren Bormann¹, Leonie Brochhagen¹, Mira Alt¹, Mona Otte¹, Laura Thümmler^{1

2}, Lukas van de Sand¹, Ivana Kraiselburd³, Alexander Thomas³, Jule Gosch³, Peer Braß¹, Sandra Ciesek^{4

5

6}, Marek Widera⁴, Sebastian Dolff¹, Ulf Dittmer⁷, Oliver Witzke¹, Folker Meyer³, Monika Lindemann², Andreas Schönfeld¹, Hana Rohn¹, Adalbert Krawczyk^{1

7}

Affiliations

¹ Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
³ Institute for Artificial Intelligence in Medicine, University Hospital Essen, Essen, Germany.
⁴ Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
⁵ Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt am Main, Germany.
⁶ Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine and Pharmacology, Frankfurt am Main, Germany.
⁷ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

Background: Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves.

Methods: The corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay.

Results: On a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT₁₀₀) 640 versus 80, p<0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT₁₀₀ of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT₁₀₀ of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants.

Conclusion: Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.

Keywords: COVID-19; Delta; Omicron; SARS-CoV-2; breakthrough infections.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Breakthrough Infections
COVID-19*
Enzyme-Linked Immunospot Assay
Humans
Immunity, Cellular
SARS-CoV-2*

Substances

Antibodies, Neutralizing

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This study was supported by the Stiftung Universitätsmedizin Essen (awarded to A. Krawczyk) and the Rudolf Ackermann Foundation (awarded to O. Witzke).