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

被引：12

作者：

Bormann, Maren ^{[1
]}

Brochhagen, Leonie ^{[1
]}

Alt, Mira ^{[1
]}

Otte, Mona ^{[1
]}

Thuemmler, Laura ^{[1
,2
]}

van de Sand, Lukas ^{[1
]}

Kraiselburd, Ivana ^{[3
]}

Thomas, Alexander ^{[3
]}

Gosch, Jule ^{[3
]}

Brass, Peer ^{[1
]}

Ciesek, Sandra ^{[4
,5
,6
]}

Widera, Marek ^{[4
]}

Dolff, Sebastian ^{[1
]}

Dittmer, Ulf ^{[7
]}

Witzke, Oliver ^{[1
]}

Meyer, Folker ^{[3
]}

Lindemann, Monika ^{[2
]}

Schoenfeld, Andreas ^{[1
]}

Rohn, Hana ^{[1
]}

Krawczyk, Adalbert ^{[1
,7
]}

机构：

[1] Univ Duisburg Essen, Univ Hosp Essen, West German Ctr Infect Dis, Dept Infect Dis, Essen, Germany

[2] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany

[3] Univ Hosp Essen, Inst Artificial Intelligence Med, Essen, Germany

[4] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Inst Med Virol, Frankfurt, Germany

[5] Goethe Univ Frankfurt, Inst Pharmaceut Biol, Frankfurt, Germany

[6] Fraunhofer Inst Mol Biol & Appl Ecol IME, Branch Translat Med & Pharmacol, Frankfurt, Germany

[7] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany

来源：

FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷

关键词：

SARS-CoV-2; breakthrough infections; Omicron; Delta; COVID-19;

D O I：

10.3389/fimmu.2023.1150667

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

BackgroundBreakthrough 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. MethodsThe 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-& gamma; ELISpot assay. ResultsOn a cellular level, patients showed a minor IFN-& gamma; 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. ConclusionNeutralizing 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.

引用

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