COVID-19 Vaccine Efficacy Reduced With Immunosuppressive, Antiviral HBV Drug Use

New research is calling attention to diminished COVID-19 vaccine efficacy in patients taking immunosuppressive drugs and hepatitis B antiviral drugs after living-donor liver transplantation, suggesting the potential benefit of additional vaccination to boost antibody levels in this patient population.1

Study findings point to differences in the dynamics of the immune response between immunocompromised individuals taking immunosuppressive drugs and those with hepatitis B who receive antiviral drugs after liver transplant. Vaccine efficacy was reduced in patients taking immunosuppressants compared with healthy controls but was notably lower in patients taking immunosuppressants and antiviral agents concurrently.1

Following the World Health Organization declaration of COVID-19 as a pandemic in March of 2020, mRNA and adenovirus-vectored vaccines were developed and administered.2 Solid organ transplant recipients are immunocompromised and therefore more susceptible to COVID-19 infection, but the efficacy of COVID-19 vaccination in patients receiving immunosuppressants and antiviral therapy following liver transplantation is not well understood.1

“During antiviral therapy, the virus can adapt to the drug and develop escape variants. This can weaken the effectiveness of the antiviral treatment and lead to resistance to vaccines or other treatment methods,” Ryunjin Lee, of the department of convergence medicine at Asan Medical Institute of Convergence Science and Technology in South Korea, and colleagues wrote.1 “However, research on the efficacy of combined antiviral therapy and vaccines is lacking.”

To address this gap in research, investigators assessed the effectiveness of the COVID-19 vaccine in patients taking immunosuppressive drugs after living-donor liver transplantation and compared this to that of healthy controls. To assess the vaccination effect on each group, investigators measured a SARS-CoV-2 S1-specific antibody in patients’ blood, collected at 6 intervals.1

The final analysis included 87 liver transplant recipients who were administered immunosuppressive drugs after transplantation. Among this group, 50 (57.5%) patients took both immunosuppressant and HBV antiviral drugs and were vaccinated with the BNT162b2 (n = 34; 68%); mRNA vaccine (mRNA-1273; n = 3; 6%); or adenoviral vector vaccine (ChAdOx1 nCoV-19; n = 13; 26%). Among the remaining 37 (42.5%) patients who received only immunosuppressants following transplantation, most were vaccinated with the BNT162b2 vaccine (n = 27; 72.9%), followed by mRNA-1273 (n = 7; 18.9%) and ChAdOx1 nCoV-19 (n = 3; 8.1%).1

Investigators additionally assessed vaccine efficacy in a healthy control group without liver transplantation comprising 134 healthcare workers. Among them, 34 received the BNT162b2 vaccine; 16 received the mRNA-1273 vaccine; and 84 received the ChAdOx1 nCoV-19 vaccine.1

Results showed levels of the SARS-CoV-2 S1-specific antibody were significantly increased in the healthy control group compared with the immunocompromised patients (P <.0001). Additionally, antibody levels were significantly lower in immunocompromised patients receiving anti-HBV treatment than in the healthy control group (P <.0001).1

When comparing the antibody levels between vaccinated individuals and healthy controls, investigators did not observe a significant difference before vaccination or after the first dose (P = .9436), but as the number of vaccine doses increased, antibody levels also increased, with the most significant differences observed between the period before vaccination and after the third dose as well as between the period after the first and third doses (P <.0001).1

Investigators additionally sought to assess vaccine-related liver damage but cited the absence of an indicator to determine liver damage specifically caused by COVID-19. Thus, they defined the pattern of liver abnormalities as alanine aminotransferase >40 U/L; aspartate aminotransferase >40 U/L; and total bilirubin 0.2–1.2 mg/dL. Based on these measures, investigators found no difference in liver function following liver transplantation before and after vaccination (P >.05), suggesting COVID-19 vaccination does not impact liver function deterioration.1

Investigators called attention to 23 patients who encountered breakthrough infections, defined as SARS-CoV-2 infections in partially or fully vaccinated participants who had never been infected with SARS-CoV-2. This occurred in 11 immunocompromised patients taking immunosuppressive drugs and 12 with hepatitis B.1

They acknowledged multiple limitations to these findings, including the small sample size and differences in the number of patients receiving each vaccine; age group bias due to the governmental vaccine policy; the absence of data on the Alpha, Beta, Gamma, Delta, and Omicron variants of COVID-19; the lack of measurement of various T cell cytokines; and the lack of consideration for the different antibody responses observed between vaccines.1

“In recipients of LDLT that are taking immunosuppressants, the efficacy of the COVID-19 vaccine was found to be lower compared to the healthy control group. However, HBV-positive individuals exhibited suboptimal responses, and our understanding of the mRNA vaccine’s effectiveness remains limited,” investigators concluded.1 “The influence of antiviral drugs on vaccine responses requires further investigation.”

References

1. Lee R, Choi J, Lee E, et al. Effects of combined immunosuppressant and hepatitis B virus antiviral use on COVID-19 vaccination in recipients of living donor liver transplantation. PeerJ. https://doi.org/10.7717/peerj.18651
2. World Health Organization. Coronavirus disease (COVID-19) pandemic. Accessed December 11, 2024. https://www.who.int/europe/emergencies/situations/covid-19