Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients

Abstract

Background and aims Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. Methods LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. Results Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. Conclusion LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. Lay summary Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive , average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

Protected or not protected, that is the question - First data on COVID-19 vaccine responses in patients with NAFLD and liver transplant recipients

“…The second study from Tel-Aviv Sourasky Medical Center, Israel, evaluated humoral antibody responses in 80 LTR and 25 healthy volunteers after vaccination with the mRNA vaccine BNT162b2 (BioNTech/Pfizer). The study confirmed the concern of lower immunogenicity of vaccination in transplant recipients (reviewed in [1]); antibodies were detectable in only 47.5% of patients compared to all 25 healthy controls and antibody titers were significantly lower in LTR (95.41 AU/mL vs. 200.5 AU/mL, p<0.001) [3]. Importantly, the authors reported no serious adverse events associated with the vaccine, and no event of graft rejection was observed.…”

“…This lead the European Association for the Study of the Liver (EASL) to publish a position paper guiding COVID-19 vaccination in patients with CLD, hepatobiliary cancer, and liver transplant recipients (LTR) [1]. In this issue, Wang et al [2] and Rabinowich et al [3] report first data on COVID-19 vaccination in patients with nonalcoholic fatty liver disease (NAFLD) and liver transplant recipients.…”

“…This may be due to distinct immunosuppressive treatments used in different transplant groups. Indeed, predictors of absence of humoral vaccine responses in both LTR [3] and KTR [5] were treatment with high-dose steroids and anti-metabolites (i.e. mycophenolate mofetil), in addition to older age and for LTR lower eGFR.…”

Anti-SARS-CoV-2 Antibodies Testing in Recipients of COVID-19 Vaccination: Why, When, and How?

“…Deepak et al observed a threefold lower generation of anti-SARS-CoV-2 spike IgG and neutralizing antibodies in patients with chronic inflammatory diseases undergoing immunosuppressive treatment compared to immunocompetent controls [24]. Similar evidence was collected from other studies in patients receiving various immunosuppressive agents after transplantation [18,[25][26][27][28] or treatment for chronic inflammatory conditions [29], but also in patients with different forms of cancer [30], especially in those with hematological malignancies [31,32], as well as in subjects with end-stage renal disease [33].…”

Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review

“…55,73 The formation of neutralizing antibodies in liver transplant recipients (especially those receiving immunosuppressants) have been suboptimal, as shown by a recent study. 74 The clinical impact of this suboptimal response remains to be seen. However, this should not deter any clinician from prescribing the vaccine in these patients.…”