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Meta-Analysis
. 2022 Apr 1;5(4):e226822.
doi: 10.1001/jamanetworkopen.2022.6822.

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

Kasama Manothummetha  1 , Nipat Chuleerarux  2 , Anawin Sanguankeo  3 , Olivia S Kates  4 , Nattiya Hirankarn  1 , Achitpol Thongkam  1 , M Veronica Dioverti-Prono  4 , Pattama Torvorapanit  5   6 , Nattapong Langsiri  1 , Navaporn Worasilchai  7 , Chatphatai Moonla  5   6 , Rongpong Plongla  5   6 , William M Garneau  4 , Ariya Chindamporn  1 , Pitchaphon Nissaisorakarn  8 , Tany Thaniyavarn  9 , Saman Nematollahi  10 , Nitipong Permpalung  1   4
Affiliations
Meta-Analysis

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

Kasama Manothummetha et al. JAMA Netw Open. .

Abstract

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 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 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Torvorapanit reported receiving grants from Health Systems Research Institute during the conduct of the study. Dr Garneau reported receiving personal fees from DKBmed and the Society of Hospital Medicine during the conduct of the study and owning stock in Abbott, Avantor, Danaher, Eli Lilly, Ecolab, Iqvia, Johnson & Johnson, Stryker, United Healthcare, and AstraZeneca outside the submitted work. Drs Worasilchai, Plongla, and Chindamporn reported receiving grants from the Health Systems Research Institute (Thailand) and Rachadapiseksompotch Fund, Chulalongkorn University outside the submitted work. Dr Permpalung reported receiving grants from Health Systems Research Institute, Fisher Center Discovery Program, Cystic Fibrosis Foundation, and National Institutes of Health, and personal fees from Shionogi and Pulmocide outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Selection Flowchart
Figure 2.
Figure 2.. Antibody Response of mRNA Vaccines
Total seroconversion includes all seroconversion regardless of humeral immune response from the previous dose. New seroconversion only includes seroconversion from patients with no or minimal immune response from the previous dose. Dark lines indicates medians; dots, means; boxes, IQRs; whiskers, ranges. aBox plot cannot be graphed because fewer than 5 studies were included.
Figure 3.
Figure 3.. Overall, Unadjusted, and Adjusted Pooled Odds Ratios (ORs) Accounting for Confounders
mTOR indicates mammalian (mechanistic) target of rapamycin.
Figure 4.
Figure 4.. Unadjusted and Adjusted Pooled Odds Ratios (ORs) Accounting for Publication Bias
mTOR indicates mammalian (mechanistic) target of rapamycin; OR, odds ratio.
See this image and copyright information in PMC

Comment in

References

    1. Boyarsky BJ, Po-Yu Chiang T, Werbel WA, et al. . Early impact of COVID-19 on transplant center practices and policies in the United States. Am J Transplant. 2020;20(7):1809-1818. doi:10.1111/ajt.15915 - DOI - PMC - PubMed
    1. Pereira MR, Mohan S, Cohen DJ, et al. . COVID-19 in solid organ transplant recipients: initial report from the US epicenter. Am J Transplant. 2020;20(7):1800-1808. doi:10.1111/ajt.15941 - DOI - PMC - PubMed
    1. Bossini N, Alberici F, Delbarba E, et al. ; Brescia Renal COVID task force . Kidney transplant patients with SARS-CoV-2 infection: the Brescia Renal COVID task force experience. Am J Transplant. 2020;20(11):3019-3029. doi:10.1111/ajt.16176 - DOI - PMC - PubMed
    1. Cravedi P, Mothi SS, Azzi Y, et al. . COVID-19 and kidney transplantation: results from the TANGO International Transplant Consortium. Am J Transplant. 2020;20(11):3140-3148. doi:10.1111/ajt.16185 - DOI - PMC - PubMed
    1. Benotmane I, Risch S, Doderer-Lang C, Caillard S, Fafi-Kremer S. Long-term shedding of viable SARS-CoV-2 in kidney transplant recipients with COVID-19. Am J Transplant. 2021;21(8):2871-2875. doi:10.1111/ajt.16636 - DOI - PMC - PubMed