key: cord-0872993-20qs5jn8
authors: van Delden, Christian
title: Is transplantation per se a risk factor for worse outcome of SARS–CoV–2 infection in kidney transplant recipients?
date: 2021-05-26
journal: Transpl Int
DOI: 10.1111/tri.13879
sha: 565a20cd0961c79b28c877ebb309e9215fa865cc
doc_id: 872993
cord_uid: 20qs5jn8

We read with great interest the recent article by Hugo et al. reporting comparable mortality following SARS-CoV-2 infection in 46 solid organ transplant (SOT) recipients compared in multivariable conditional logistic regression to 1380 controls without transplantation matched for known COVID-19 risk factors (1), and the responding letter by Budde et al. suggesting misinterpretation of the data due to a selection bias of the control population (2). The latter fear that misleading conclusions could have detrimental effects on decision making concerning risk-stratification and immunizations strategies.

We read with great interest the recent article by Hugo et al. reporting comparable mortality following SARS-CoV-2 infection in 46 solid organ transplant (SOT) recipients compared in multivariable conditional logistic regression to 1380 controls without transplantation matched for known COVID-19 risk factors [1] , and the responding letter by Budde et al. suggesting misinterpretation of the data due to a selection bias of the control population [2] . The latter fear that misleading conclusions could have detrimental effects on decision making concerning risk-stratification and immunizations strategies.

Since the beginning of the SARS-CoV-2 pandemic and through the different waves that hit our countries, overwhelmed healthcare systems with triage for access to life-saving ventilator support, different thresholds for intubation, evolving ventilation techniques including lung protective strategies, high-flow nasal cannula or non-invasive positive pressure ventilation [3] , as well as multiple treatment strategies including hydroxychloroquine, azithromycin, lopinavir/ritonavir (mostly used during the first wave), and dexamethasone, remdesivir, tocilizumab, convalescent plasma (mostly during the second wave), altogether led to mortality rates that largely fluctuated, decreased for instance in Spain from 24% to 13.2% between the first and second wave [4] , and largely limit comparisons between studies and populations. Except for dexamethasone, reports on favourable effects of the various used medications are scarce, most being without any notable beneficial effect [5] . Although specific risk factors for severe outcome; including age, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease and basal renal function have been identified, it remains unclear how pre-existing SOT influences COVID-19 outcome [6, 7] .

Whereas initial reports during the first wave from New York suggested increased mortality in SOT recipients with COVID-19 [8] , a first experience from the Swiss Transplant Cohort Study (STCS) limited to 21 SOT recipients suggested the absence of higher rates of complications as compared to the general population [9] . It was hypothesized that immunosuppressive regimens of SOT recipients might be protective against the hyperinflammation responses contributing to ARDS development in COVID-19. Since then, several reports have presented conflicting results concerning the severity and mortality rates of SOT recipients with COVID-19 [10] [11] [12] [13] [14] . SOT recipients might not all be at the same risk for worse outcome, depending on the type of transplant and underlying diseases, belonging to the above cited and well-established risk factors [15] . Obviously, lung transplant recipients with preexisting impaired and fragile lungs are potentially at higher risk for complications than other types of transplant recipients. In the same line, kidney transplant recipients (KTR) might also be at increased risk for complications due to their frequent underlying comorbidities including diabetes, hypertension, cardiovascular diseases and reduced renal function. Recently, Chavarot et al tried to decipher the influence of both immunosuppression and comorbidities on the outcome of KTR with COVID-19 using a propensity score matching [16] . Their study, including 83 KTRs matched to 83 controls from non-transplanted patients comparable in terms of age, sex and comorbidities, suggested that kidney transplantation per se was not associated with a higher risk of complications or mortality, thereby supporting the observation by Hugo et al. In the light of the limitations for study comparisons expressed above, how can we now integrate the results presented by Hugo et al. and the concerns of Budde et al.? At the time being, it seems reasonable to assume that kidney transplantation per se might not be associated with worse outcome, but that underlying comorbidities of kidney transplant recipients might influence the outcome similarly as in the general population. Therefore, kidney transplant recipients, as well as all other SOT recipients with comorbidities, should remain a priority population for immunization strategies. It remains also to be evaluated whether the risk of severe COVID-19 in patients dialysed while on the kidney transplant waiting list differs compared to the risk of those having received a kidney transplant, once matched for associated comorbidities (17).

Solid organ transplantation is not a risk factor for COVID-19 disease outcome

Undoubtedly, kidney transplant recipients have a higher mortality due to COVID-19 disease compared to the general population

Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS

First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus

Drug treatments for covid-19: living systematic review and network meta-analysis

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter

First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Coronavirus disease 2019 in kidney transplant recipients: single-center experience and case-control study

Kidney transplant patients with SARS-CoV-2 infection: The Brescia Renal COVID task force experience

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study

Is COVID-19 infection more severe in kidney transplant recipients?

Early experience with COVID-19 and solid organ transplantation at a US high-volume transplant center

COVID-19 in solid organ transplant: A multi-center cohort study