SARS-CoV2-specific Humoral and T-cell Immune Response After Second Vaccination in Liver Cirrhosis and Transplant Patients

Abstract

Background and Aims Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against SARS-CoV-2 is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups. Methods In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S Trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10-84 days after second vaccination. The spike-specific T-cell response was assessed using an IFN-γ release assay (IGRA, EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response. Results After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S Trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared to cirrhotic patients and controls (p<0.001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age >65y (OR: 4.57, 95%-CI 1.48-14.05) and arterial hypertension (OR: 2.50, 95%-CI 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR: 0.36, 95%-CI 0.13-0.99). Conclusion Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients

“…No sex differences in the rate of long-term vaccine antibody response were detected. This agrees with previous reports 11,18,22 but is in contrast to what was reported in LT recipients by Herrera et al 19 , who documented a significantly lower response rate in females. However, this difference may be due to the different vaccine types (mRNA1273) adopted in these patients compared to BNT162b2 adopted in our patients.…”

“…Moreover, the peak of responder patients J o u r n a l P r e -p r o o f was reached four months after the second vaccine dose and remained stable up to six months. Recent reports indicated that the rate of antibody response to anti-SARS-CoV-2 vaccination in LT patients ranged from 45.5% to 82% 11,12,16,[18][19][20][21][22] , which is comparable to what we observed. However, all these studies evaluated the early (up to 3 months) immune response to vaccination.…”

“…Furthermore, only 4 patients adopting triple immunosuppression were enrolled in our study. The influence of eGFR in conditioning the antibody vaccine response has seldom been evaluated in studies 11,12,19,22 . In our series, a lower eGFR was selected as a negative predictor of vaccine response only three weeks after the first dose and not thereafter, which may be considered in agreement with what has been demonstrated in other series 22 .…”

Humoral Immune Response following SARS-CoV-2 Vaccination in Liver Transplant Recipients

“…However, the importance of the quantitative level of circulating antibodies, IgG and IgA, to this respiratory infection remains unclear, taking issues such as t-cell-mediated immunity and the definition of neutralizing antibodies into account. Ruether et al, in whose cohort of LT recipients a seroconversion rate of 63% regarding anti-spike-protein-IgG was achieved, detected a spike-specific T-cell response in 36.6% in the same cohort compared to a cohort of patients with liver cirrhosis and healthy controls, who both developed anti-spike-protein-IgG in 100% of the cases and had a spikespecific T-cell response in 65.4 and 100% of the cases, respectively [26]. Westhoff et al detected a seroconversion rate of 60% and anti-spike-specific T-cells in 90% of kidney transplant recipients following a third dose of mRNA-based vaccine following initial humoral nonresponse following the second dose [27].…”

Management of COVID-19 patients with chronic liver diseases and liver transplants

“…Double-negative patients even accounted for 28%. For patients with liver cirrhosis in this cohort, the serum conversion rate after the second vaccination can reach 100% [66] . Based on the above research and position statements issued by the EASL and AIFA [ 67 , 68 ], the following suggestions are listed for reference: [1] Patients with noncirrhotic NAFLD and ALD seem to be at high risk of severe COVID-19.…”