**1. Introduction**

Few centers across the globe have reported on the outcomes of COVID-19 in lung transplant recipients (LTRs) [1–6]. Most reports relate to the early period following the declaration of the COVID-19 pandemic in March 2020 by the World Health Organization. These initial reports, predominately of hospitalized LTRs with short-term follow-ups, showed high hospitalization and mortality rates associated with COVID-19. The mortality rate of COVID-19-related acute respiratory distress syndrome (ARDS) requiring invasive

**Citation:** Franco-Palacios, D.J.; Lu, M.; Fitzmaurice, M.G.; Alangaden, G. Outcomes of COVID-19 in a Large Cohort of Lung Transplant Recipients: A Retrospective Study. *Transplantology* **2022**, *3*, 257–266. https://doi.org/10.3390/ transplantology3030026

Academic Editors: Macé M. Schuurmans and René Hage

Received: 27 May 2022 Accepted: 14 July 2022 Published: 22 July 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/).

mechanical ventilation was significantly higher in LTRs than in the immunocompetent patient population (75–100% versus 20–40%, respectively) [7–9], even if compared with non-immunosuppressed patients with severe refractory hypoxic respiratory failure on venovenous extracorporeal membrane oxygenation (vvECMO). In a registry of 1900 solid organ transplant (SOT) recipients with COVID-19, including over 150 LTRs, the morbidity and mortality rates were higher for LTRs compared with other SOT recipients [10].

Since these early reports, the modalities used for the treatment and prevention of COVID-19 have rapidly evolved. Remdesivir, an antiviral agent administered to hospitalized patients with moderate illness who did not require hospitalization into an intensive care unit (ICU), was shown to shorten the time to clinical recovery [11,12]. In patients with COVID-19-related pneumonia and hypoxic respiratory failure, landmark studies of corticosteroid therapy demonstrated significant improvement in outcomes and reduced mortality [13]. Favorable outcomes were reported with the use of immunomodulators, such as tocilizumab and baricitinib, in addition to corticosteroids in patients with severe and critical COVID-19 [12,14]. The use of anticoagulation to prevent venous thromboembolism (VTE); high quality critical care, including treatment of secondary infections; the support of other organs; and the avoidance of further damage by the ventilator or self-induced lung injury are standard of care. Venous thromboembolism prevalence was found to be higher in COVID-19 patients than in other ICU patient populations [15]. In noncritically ill patients with COVID-19, an initial strategy of therapeutic-dose anticoagulation with heparin was associated with better outcomes [16]. These modalities were incorporated into guidelines endorsed by several medical societies for the treatment of COVID-19, utilizing a tiered approach based on the severity of illness [17]. Additionally, the modification of immunosuppression (corticosteroid augmentation and the discontinuation of cell-cycle inhibitors) was recommended in SOT recipients (SOTRs) [18,19].

In December 2020, messenger RNA vaccines received an Emergency Use Authorization in the United States of America. The effectiveness of these vaccines was noted to be suboptimal in SOTRs due to the immunosuppressant therapies used to prevent rejection and an attenuated immune response [20]. Vaccine effectiveness was further compromised by the emergence of variants of SARS-CoV-2 [21]. Other therapies aimed to prevent serious illness in this high-risk population became available over time, including different compositions of monoclonal antibodies and oral antivirals [22].

However, the effect of these new modalities of therapy on the outcomes of COVID-19 in the LTR population is incompletely understood. We described the clinical course and outcomes of COVID-19 in 59 LTRs, as well as the incidences of vaccine-breakthrough infections from March 2020 to March 2022 at our institution. The primary outcome of interest for our study was examining the risk of COVID-19-related hospitalization and inpatient mortality.
