Comparison of COVID-19 outcomes in organ transplant recipients (OTr) and non-transplant patients: a study protocol for rapid review

Abstract

Background The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. Methods MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. Discussion This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. Systematic review registration Open Science Framework (OSF) registration DOI: 10.17605/osf.io/4n9d7.

Clinical characteristics and comorbidities associated with SARS-CoV-2 breakthrough infection in the University of California Healthcare Systems

“…While the risk for transplant recipients is well-documented due to the suppression of the immune system, the substantially higher risk of breakthrough infection for these patients compared to those with other known risk factors of COVID-19 (such as heart and cardiovascular diseases) was not previously known. 30 Our findings, that those with lung transplants are at highest risk for breakthrough infection amongst other solid organ transplant recipients are substantiated by the characteristics of COVID-19 as a respiratory disease and the important role of Antigen-Converting Enzyme 2 (ACE2) receptor in inducing viral entry in the lung epithelium, leading to infection and disease severity. 31 , 32…”