ABSTRACT
Introduction: Liver 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 cirrhotic patients and 39 healthy controls after two and three doses of mRNA COVID-19 vaccination. Aims & Methods: SARS-CoV-2-specific T cell reactivity was measured by induced level of T cell-derived interferon-gamma (IFN-gamma) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-gamma was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna), while serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG) were quantified after the 1st, 2nd and third dose of the vaccine. Result(s): T cell reactivity against S1 was reduced in cirrhotic patients after the 1st (P<0.001 vs controls) and 2nd (P<0.001) vaccination. Sixty-eight % of patients lacked detectable S1-specific T cell reactivity after the 1st vaccination vs. 19% in controls (OR 0.11, HR 0.03-0.48, P=0.003) and 36% remained devoid of reactivity after the 2nd vaccination vs. 6% in controls (OR 0.12, HR 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. Anti-RBD IgG levels were increased significantly after the 3rd compared to the 2nd dose (median 944 vs. 563 BAU/ml, p=0.002). Hybrid immunity, i.e., the combined effect of vaccination and naturally acquired COVID-19, was associated with significantly higher antibody levels (>5680 (821->5680) vs 944 (5-5675)) BAU/ml, p=0.0001) as compared to antibody levels achieved through 3 doses of vaccination alone. The time elapsed between vaccination to blood draw after the 3rd dose of the vaccine was significantly longer than after the 2nd dose (90 vs 118 days, p < 0.001). Conclusion(s): Cirrhotic patients show deficient T cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination. Nevertheless, a third dose of mRNA COVID-19 vaccine generally results in high antibody levels, and hybrid immunity following naturally acquired infection elicits further augmented levels in patients with cirrhosis. As immune waning is of concern with regards to COVID-19, continued vigilance as well as iterated booster vaccine doses for these vulnerable patients is likely prudent.