Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination
Samer Al-Dury,
Johan Waern,
Jesper Waldenström,
Marko Alavanja,
Hevar Hamah Saed,
Andreas Törnell,
Mohammad Arabpour,
Hanna Grauers Wiktorin,
Sigrun Einarsdottir,
Johan Ringlander,
Gisela Ringström,
Kristoffer Hellstrand,
Anna Martner,
Martin Lagging
Affiliations
Samer Al-Dury
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
Johan Waern
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
Jesper Waldenström
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Marko Alavanja
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
Hevar Hamah Saed
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
Andreas Törnell
TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Mohammad Arabpour
TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Hanna Grauers Wiktorin
TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Sigrun Einarsdottir
Department of Hematology and Coagulation, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
Johan Ringlander
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
Gisela Ringström
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
Kristoffer Hellstrand
TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
Anna Martner
TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Martin Lagging
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden; Corresponding author. Address: Department of Infectious, /VirologySahlgrenska University Hospital and University of Gothenburg, 413 45 Gothenburg, Sweden
Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-γ was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p <0.001 vs. controls) and 2nd (p <0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1st vaccination vs. 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, p = 0.003) and 36% remained devoid of reactivity after the 2nd vaccination vs. 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, p = 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses (p <0.05 vs. Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1st (p <0.001 vs. controls) and 2nd (p <0.05) vaccination. Conclusions: Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures. Clinical trial registration: EudraCT 2021-000349-42 Lay summary: T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients.
