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

• Published in: Frontiers in immunology 2023-07, Vol.14, p.1150667-1150667
• Main Authors: Bormann, Maren, Brochhagen, Leonie, Alt, Mira, Otte, Mona, Thümmler, Laura, van de Sand, Lukas, Kraiselburd, Ivana, Thomas, Alexander, Gosch, Jule, Braß, Peer, Ciesek, Sandra, Widera, Marek, Dolff, Sebastian, Dittmer, Ulf, Witzke, Oliver, Meyer, Folker, Lindemann, Monika, Schönfeld, Andreas, Rohn, Hana, Krawczyk, Adalbert
• Format: Article
• Language: English
• Subjects: breakthrough infections; COVID-19; Delta; Immunology; Omicron; SARS-CoV-2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1150667

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. 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. 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 (NT ) 640 versus 80, p