ABSTRACT
Background and Aims: SARS-CoV-2 mRNA vaccines have been approved to prevent COVID-19. We assessed immunogenicity, effectiveness and safety of vaccines in patients with compensated and decompesated cirrhosis. Method: This is a prospective single center study assessing humoral and cellular responses in cirrhotics compared to healthy controls, incidence post-vaccination SARS-CoV-2 infections and adverse events (AEs). Antibodies against the spike- and nucleocapside-protein (anti-S and anti-N) were tested at baseline, 21 days after the first and second doses and during follow-up. Spike-specific T-cells quantity assessment was longitudinally conducted by the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by IFN-γ and IL-2 measurement. Results: 182 cirrhotics (61 years, 75% males, 45% viral-related, 74% Child-Pugh A, 31% HCC, 85% COVID-19 naïve) and 38 healthy subjects were enrolled. Previous SARS-CoV-2 infection predicted higher anti-S titres at all time points after vaccination, in both groups. COVID-19 naïve cirrhotics showed significantly lower anti-S titres compared to controls [998.5 (0.4-12,500) vs 1,520 (259-12,500) U/mL, p=0.048], anti-S titres significantly decreased after a median of 133 (70-182) days [536 (0.4-8,777) U/mL, p<0.0001] and were lower in decompensated vs compensated cirrhosis [632 (0.4-12,500) vs 1,377 (0.4-12,500) U/mL, p=0.028]. By multivariable analysis in COVID-19 naïve cirrhotics, independent predictors of lower anti-S were active HCC, immunocompromised conditions, BNT162b2 and lower anti-S after first dose. The spike-specific T-cell response was evaluated in 14 cirrhotics, showing a heterogeneous magnitude of response, but on average the quantity and kinetics of decline of the spike-specific cellular responses diverged in cirrhotics compared to controls, with lower concentrations of both IFN-γ and IL-2. During follow-up, 4/133 (3%) COVID-19 naïve cirrhotics tested positive for anti-N, all asymptomatic. Neither unexpected nor severe AEs emerged. Conclusion: Humoral and cellular responses to SARS-CoV-2 mRNA vaccines appeared suboptimal in patients with cirrhosis, however the rate of post-vaccination infection seems low.