Immunogenicity and Risk Factors Associated with Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis

Importance: Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. Objective: To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT. Data Sources: A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Study Selection: Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed. Data Extraction and Synthesis: Two 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 Measures: The 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. Results: A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11713 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 Relevance: In 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.. © 2022 American Medical Association. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Characterization of Respiratory Pathogens in Contemporary Lung Transplant Recipients

Copyright © 2020. Published by Elsevier Inc. PURPOSE: This study assessed respiratory pathogens isolated in the first year post lung transplant in a recent multicenter cohort. Prior studies may not reflect current practices in antimicrobial prophylaxis and molecular diagnostics. METHODS: We examined 499 consecutive bronchoalveolar lavage (BAL) samples for microbial isolates in 82 lung transplant recipients (LTR) enrolled in the prospective Genomic Research Alliance for Transplantation from July 2015 to 2017. Isolates were examined for species, timing: early (0-1 months post-transplant (MPT), intermediate (1-6 MPT), and late (6-12 MPT), and associated lung function decline. RESULTS: 389 microbes were isolated in 499 BAL samples, representing 348 unique episodes, over a median of 196 days. Bacterial isolates were more common in the early and intermediate periods, and fungal and viral pathogens more common in the late period. In non-Cystic Fibrosis (CF) populations, the frequencies of most common bacterial isolates S. aureus, P. aeruginosa, and enteric Gram Negative Bacteria were 15.6%, 12.6%, 23.0%, compared to 28.0%, 30.0%, and 18.0% respectively, in CF LTRs. The most common viral pathogens were rhinovirus (60.6%), and enterovirus (12.7%). Non-invasive molds (Penicillium etc) comprised 73.3% of fungal isolates, with potentially invasive molds (Aspergillus, Mucor sp.) isolated in 12.9% of cases. Notably, there were only two isolates of Aspergillus fumigatus (2.0%). 48/389 isolates (12.3%) were associated with \u3e 10% reduction in FEV1 at 90 days post isolation of which rhinovirus was the most frequent isolate (11/48). CONCLUSION: In a contemporary cohort, bacterial pathogens predominate in the early post-transplant period, while fungal and viral pathogens are more common later. Pseudomonas and Aspergillus sp. comprised a smaller proportion of total than previously described, and do not appear to associate with early lung function decline. Further studies are underway to determine the conditions in which select infections impact early lung function