**1. Introduction**

In January 2020, a novel coronavirus now known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan City, China [1]. The World Health Organization announced SARS-CoV-2 as a Public Health Emergency Concern and declared the viral outbreak a pandemic in March 2020 [2]. Exactly two years since, the U.S. has had more than 79 million confirmed SARS-CoV-2 cases and almost one million fatalities [3]. During the same period, over 452 million cases and 6 million SARS-CoV-2-related deaths have been reported globally [4].

As has been previously discussed by this research group and others, individuals that have received liver and kidney transplants are at a significantly heightened risk for morbidity and mortality from SARS-CoV-2 infection compared to the general population [5–14]. Liver- and kidney-transplant recipients have higher rates of diabetes, obesity, hypertension, and cardiovascular disease, which have all been identified as risk factors for severe SARS-CoV-2 complications in early reports at our institution and by others [6,8,11,15–18].

**Citation:** Hardgrave, H.; Wells, A.; Nigh, J.; Osborn, T.; Klutts, G.; Krinock, D.; Rude, M.K.; Bhusal, S.; Burdine, L.; Giorgakis, E. SARS-CoV-2 Infection of Unvaccinated Liver- and Kidney-Transplant Recipients: A Single-Center Experience of 103 Consecutive Cases. *Transplantology* **2022**, *3*, 200–207. https://doi.org/10.3390/ transplantology3020021

Academic Editor: Macé M. Schuurmans

Received: 13 April 2022 Accepted: 10 June 2022 Published: 16 June 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Early anecdotal experience [8] and later reports have reported a higher mortality risk among kidney-transplant recipients following SARS-CoV-2 infection compared to the livertransplant recipients [19], with both groups having higher hospitalization and intensivecare-unit-admission rates. These early observations were debated in the later periods of the pandemic. This perhaps reflects the higher quality of care and closer surveillance of the transplant patients compared to the general population as well as the better understanding of the disease pathophysiology and effective treatments as the pandemic evolved, among other reasons [6,7,9,11,12,14,15,17,20,21].

Despite the plethora of published reports, the role of immunosuppression in SARS-CoV-2 severity in post-transplant patients remains unclear: Standard immunosuppression could potentially suppress the immune system's capacity to mount a sufficient response to neutralize the viral insult, modulate systemic inflammatory storm, or suppress viral replication [5,6,9,11,13,15,20–27]. By convention, most transplant clinicians modify the maintenance of immunosuppression in transplant patients infected by SARS-CoV-2, frequently by decreasing or even discontinuing antimetabolites [6,12,13,15,23,24,27]. The international society for heart and lung transplantation has officially recommended consideration for using mycophenolate mofetil, mTOR inhibitors, and azathioprine in transplant patients with moderate to severe SARS-CoV-2 [28]. Virus-targeted immunotherapies, i.e., monoclonal antibodies (MABs) and convalescent plasma have emerged as potential treatments. Studies have reported a decrease in hospitalization need and mortality rates following the use of MABs in high-risk groups, such as the immunocompromised transplant recipients [29–31].

This study aimed to study the SARS-CoV-2-specific mortality and associated risk factors of a cohort of 103 consecutive unvaccinated solid-organ-transplant recipients that were transplanted at a single academic transplant center, using a prospectively populated institutional SARS-CoV-2 transplant registry.
