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Humoral Immunogenicity to SARS-CoV-2 Vaccination in Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

ABSTRACT: Solid organ transplant recipients generally show reduced immunogenicity to various vaccines. We aimed to assess the immunogenicity of the immune response among orthotopic liver transplant (OLT) recipients after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A systematic search was performed to evaluate immunogenicity or adverse events reported after SARS-CoV-2 vaccination. The pooled analysis of 20 studies showed a humoral immune response rate of 0.70 (95% confidence interval [CI], 0.63-0.77) after SARS-CoV-2 vaccination among OLT recipients. The immunogenicity among OLT recipients was significantly lower compared to the overall population and healthy controls, with odds ratios (ORs) of 0.80 and 0.69. However, it was significantly higher than that of patients receiving other organ transplants, especially kidneys, with an OR of 1.50. Male sex, old age, chronic kidney disease, obesity, and multiple or high immunosuppressant doses significantly increased the risk of unresponsiveness in patients with OLT. The overall incidence of any adverse event after vaccination was 0.68 (95% CI, 0.55-0.81), similar to that of control. OLT recipients had an overall humoral immune response rate of 70% after SARS-CoV-2 vaccination, which is lower than that of healthy controls but favourable compared to those of other solid organ transplant recipients.

SUBMITTER: Yoo JJ

PROVIDER: S-EPMC9576515 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Humoral Immunogenicity to SARS-CoV-2 Vaccination in Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

Yoo Jeong-Ju JJ Yon Dong Keon DK Lee Seung Won SW Shin Jae Il JI Kim Beom Kyung BK

International journal of biological sciences 20220921 15

Solid organ transplant recipients generally show reduced immunogenicity to various vaccines. We aimed to assess the immunogenicity of the immune response among orthotopic liver transplant (OLT) recipients after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A systematic search was performed to evaluate immunogenicity or adverse events reported after SARS-CoV-2 vaccination. The pooled analysis of 20 studies showed a humoral immune response rate of 0.70 (95% confiden ...[more]

PMID: 36263175

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Project description:Background & aimsTwo 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 of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population.MethodsLT 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.ResultsEighty 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 estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group.ConclusionLT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population.Lay summaryThe Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

Project description:BackgroundImmunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.MethodsAll LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.ResultsNinety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001).ConclusionsAmong LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.

Project description:ImportanceRecipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination.ObjectiveTo summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT.Data sourcesA literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov.Study selectionStudies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed.Data extraction and synthesisTwo reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022.Main outcomes and measuresThe total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response.ResultsA total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%).Conclusions and relevanceIn this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.

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Humoral Immunogenicity to SARS-CoV-2 Vaccination in Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

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Humoral Immunogenicity to SARS-CoV-2 Vaccination in Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

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