key: cord-1000517-zyj36h1n authors: Cornberg, Markus; Eberhardt, Christiane S. title: Protected or not protected, that is the question - First data on COVID-19 vaccine responses in patients with NAFLD and liver transplant recipients date: 2021-05-25 journal: J Hepatol DOI: 10.1016/j.jhep.2021.05.007 sha: 1e8349891396a202701dbcad731816c66007be3f doc_id: 1000517 cord_uid: zyj36h1n nan Immunocompromised and cancer patients were excluded from the phase III trials of current COVID-19 vaccines and data from very few study participants with chronic liver disease (CLD) were not reported in detail. 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. In a multicenter study in China, Wang [4] and rates of adverse events were comparable. However, detailed characterization of the CLD in terms of liver function tests and fibrosis stages is not described and it is uncertain whether patients with advanced CLD and cirrhosis, most at risk for severe COVID-19 outcome, were included. Reported patients were rather young (median age 39 years) and only 3.7% had diabetes mellitus, a main risk factor for steatohepatitis and disease progression. This suggests that study participants had no advanced CLD and might explain why these findings are different to what is seen with other vaccines, such as influenza, where patients with advanced CLD elicit lower humoral immune responses [1] . More data on COVID-19 vaccination in patients with advanced CLD and with different vaccine types are eagerly awaited. 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 is consistent with other early real-world reports in transplant recipients vaccinated with Moderna or BioNTech/Pfizer mRNA vaccines, in whom similarly no graft rejections were observed during the early follow-up period [5, 6] . The same group evaluated vaccine responses in 136 kidney transplant recipients (KTR) and reported even lower antibody responses following vaccination with BNT162b2 and only 37.5% of KTR had detectable SARS-CoV-2 specific antibodies [5] . Compared to LTR, seropositivity rates and mean antibody titers were lower in KTR [5] , matching previous J o u r n a l P r e -p r o o f reports that transplant recipients other than LTR generally have a lower humoral response to vaccination [7] . 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. In summary, the two studies published here indicate that the humoral response to COVID-19 vaccination does not appear to be impaired in patients with hepatic steatosis when vaccinated with an inactivated vaccine but is lower in immunosuppressed LTR vaccinated with an mRNA vaccine. As expected, the quality and extent of immunosuppression is an important factor contributing to vaccine responses. However, many questions remain open. Most importantly, there is no correlate of protection for COVID-19 to date, and therefore it is difficult to interpret antibody levels. Phase I/II trails have shown that especially mRNA and viral vector COVID-19 vaccines elicit T cell responses that mightin addition to humoral responses -play a role in protection [8, 9] . Vaccine efficacy in preventing symptomatic COVID-19 even in healthy individuals ranges between around 70 and 95%, depending on the type of vaccine (reviewed in [1] ). Thus, it is expected that SARS-CoV-2 infection and cases of COVID-19 pneumonia will also occur in CLD or transplant recipients, as it has been reported in KTR, who were fully vaccinated with the BNT162b2 mRNA vaccine [10] . Here, a more severe COVID-19 course may have been prevented due to vaccination. A post-hoc subgroup analysis of vaccine efficacy in 1674 immunocompromised vaccinated individuals from Israel showed that more than 80% of these vaccinees were protected from symptomatic COVID-19 [11] . These data need cautious interpretation given the sample size (solid-organ recipients constituted only a small minority of the subgroup) and design as effectiveness study but shed a light of hope that immunized immunocompromised patients might still be protected, especially from severe COVID-19. Therefore, it is of utmost importance that registries are established to document the clinical outcome following COVID-19 vaccination in the patient populations mentioned here. This will help provide valuable information for their optimal management and provide insights into whether additional vaccine doses are needed or whether specific vaccines are more effective in this setting. In addition, the best timing for vaccination after transplantation needs to be determined to elicit a protective responses without unnecessarily delaying vaccination. Furthermore, studies now demonstrate that mRNA or viral vector COVID-19 vaccination decreases the risk of being an asymptomatic carrier [12] or transmission within the household [13] . This highlights the importance of vaccinating close contacts and health care professionals to reduce the risk of exposure for the immunocompromised individuals. where it still reduces morbidity and mortality in vaccinated compared to unvaccinated transplant recipients [14] , COVID-19 vaccination may still confer some benefit and reduce the risk or severity of COVID-19. It is therefore encouraging to see that the acceptance rate for COVID-19 vaccination in liver transplant recipients in Genoa is over 95% [15] and prompts healthcare professionals to provide necessary counsel to help taking an informed decision and to thus increase COVID-19 vaccination adherence in vulnerable patients, their close contacts and among healthcare professionals. EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): a multicenter study Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus Safety of the First Dose of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients Serologic vaccination response after solid organ transplantation: a systematic review vaccine BNT162b1 elicits human antibody and TH1 T cell responses T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial SARS-CoV-2 infection after two doses of mRNA vaccine in renal transplant recipients Reply to BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting Impact of vaccination on household transmission of SARS-COV-2 in England Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice High acceptance rate of COVID-19 vaccinationin liver transplant recipients