key: cord-0749851-3xd6t7tb
authors: Manothummetha, Kasama; Chuleerarux, Nipat; Sanguankeo, Anawin; Kates, Olivia S.; Hirankarn, Nattiya; Thongkam, Achitpol; Dioverti-Prono, M. Veronica; Torvorapanit, Pattama; Langsiri, Nattapong; Worasilchai, Navaporn; Moonla, Chatphatai; Plongla, Rongpong; Garneau, William M; Chindamporn, Ariya; Nissaisorakarn, Pitchaphon; Thaniyavarn, Tany; Nematollahi, Saman; Permpalung, Nitipong
title: 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
date: 2022-04-12
journal: JAMA Netw Open
DOI: 10.1001/jamanetworkopen.2022.6822
sha: 115564ac8f44920566cf337ca86df585415c20bf
doc_id: 749851
cord_uid: 3xd6t7tb

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]; I(2) = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I(2) = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I(2) = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I(2) = 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.

Deceased donor status 10 1,891 

exp COVID-19/ or (COVID-19 or SARS-CoV-2 or 2019 Novel Coronavirus or 2019-nCoV).mp

JNJ-78436735 or Ad26COVS1 or VAC31518).mp

AZD1222 or ChAdOx1 nCoV-19 or AZ or astrazeneca or ChAdOx1-S or AZD2816).mp

BNT162b2 or Pfizer or biontech or Comirnaty or Tozinameran).mp

Coronavac or Sinovac or PiCoVacc).mp

mRNA-1273 or Moderna).mp

WIV04 and HB02) or Sinopharm).mp

exp Vaccination/ or exp Vaccines/ or vaccin*.mp

exp COVID-19 Vaccines/ or ((COVID-19 or SARS-CoV-2 or 2019 Novel Coronavirus or 2019-nCoV) adj2 Vaccin*).tw

ALL=(COVID-19 OR SARS-CoV-2 OR 2019 Novel Coronavirus OR 2019*nCoV)

ALL=(vaccin* or immuni*ation)

ALL=(Ad26*COV*S OR JNJ*78436735 OR Ad26COVS1 OR VAC31518)

ALL=(AZD1222 or ChAdOx1 nCoV*19 or ChAdOx1*S or AZD2816)

ALL=(BNT162b2 or biontech or Comirnaty or Tozinameran)

ALL=(Coronavac or Sinovac or PiCoVacc)

ALL=(mRNA-1273 or Moderna)

ALL=(WIV04 and HB02) or Sinopharm)

MeSH descriptor: [COVID-19] explode all trees 2. COVID-19 OR SARS-CoV-2 OR 2019 Novel Coronavirus OR 2019*nCoV 3

Vaccin* OR immuni*ation 5. (#1 OR #2) AND (#3 OR #4)

MeSH descriptor: [COVID-19 Vaccines] explode all trees

OR Ad26COVS1 OR VAC31518 8. AZD1222 or ChAdOx1 nCoV*19 or AZ or astrazeneca or ChAdOx1*S or AZD2816

BNT162b2 or Pfizer or biontech or Comirnaty or Tozinameran 10. Coronavac or Sinovac or PiCoVacc 11. mRNA-1273 or Moderna 12. (WIV04 and HB02) or Sinopharm 13. #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12

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