*3.1. Patient Characteristics, Clinical Course, and Management*

A query of all 170 LTRs routinely followed-up with our program identified 59 LTRs with symptomatic COVID-19 from March 2020 to March 2022: a cumulative incidence of 34.7%. Five LTRs were diagnosed with SARS-CoV-2 twice and their disease severities varied, with only one patient hospitalized twice during each COVID-19 diagnosis. The most common symptoms of COVID-19 at presentation were dyspnea, nausea, vomiting, fever, diarrhea, and cough. A CT scan of the chest was available in 27 of 34 (79%) cases of hospitalized patients. Bilateral ground-glass opacities (GGO) were present in 70% of cases, and single-lung GGO was present in 30%. The time from the COVID-19 diagnosis to CT chest scan was a median of 2 days (IQR 0–11 days).

Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in these 59 patients, of whom 34 (57.6%) were hospitalized. Most patients in this cohort underwent bilateral LT for idiopathic interstitial pneumonia (38%) or chronic obstructive pulmonary disease (20.6%). Other indications included fibrotic interstitial lung disease associated with connective tissue diseases, sarcoidosis, pulmonary artery hypertension, cystic fibrosis, and e-cigarette- or vaping-use-associated lung injury (in one patient, the first case ever described of LT for this indication in the USA [24]). Three patients underwent dual organ transplants with bilateral LT (one heart–lung and two liver–lung), and another patient underwent redo bilateral LT for advanced bronchiolitis obliterans syndrome.

The baseline characteristics of thirty-four hospitalized and twenty-five non-hospitalized patients are summarized in Table 1. The median age at diagnosis was 64 years, 62% were males, 66% Caucasians, and 27% were African Americans. The two groups were generally comparable, except hospitalized patients were more likely to be women and African Americans. The median FEV1 (mL) prior to COVID-19 was lower in hospitalized patients at 1675 (IQR 1440–2100) compared with 2400 (IQR 1620–2790) in non-hospitalized patients (*p* = 0.01) (Supplementary Materials).

The maintenance immunosuppression regimen for most LTRs consisted of a combination of corticosteroids and a calcineurin inhibitor. A cell-cycle inhibitor was part of the regimen in 47% and rapamycin in 13% of patients at baseline. Most patients (77%) were receiving azithromycin for bronchiolitis obliterans syndrome prophylaxis. The mean time post-LT to COVID-19 diagnosis was 5.4 years (±4.8). No cases were reported in newly transplanted patients (<6 months post-LT). All cases were acquired through community exposure to cases of COVID-19 within their households. The largest number of COVID-19 cases occurred during the period of Delta variant activity (19 patients; 10 LTRs required hospitalization). Monoclonal antibodies (casirivimab-imdevimab, bamlanivimab-etesivimab, and bebtelovimab or sotrovimab), based on CDC recommendations, were administered to 14 patients at the outpatient setting. Two of them required hospitalization and there were no deaths.

Of the 34 LTRs with COVID-19 that were hospitalized for hypoxic respiratory failure secondary to SARS-CoV-2 infection, one patient was hospitalized twice for separate infection episodes.

The standard of care of hospitalized COVID-19-infected LTRs was based on institutional protocols. Frequently used therapies in our hospital include augmented corticosteroids, remdesivir, tocilizumab or baricitinib, supplemental oxygen, anticoagulation, and supportive care, as clinically indicated. Intravenous remdesivir was only administered to hospitalized patients (55%, 19/34), and IV tocilizumab was administered in four cases of critical COVID-19 without contraindications (two patients in the ICU did not receive IV tocilizumab due to an active infection). Baricitinib was used in only one patient.


**Table 1.** Baseline characteristics of hospitalized and non-hospitalized lung transplant recipients with COVID-19.

LT, lung transplant; BOS, bronchiolitis obliterans syndrome; CKD, chronic kidney disease; CLAD, chronic allograft dysfunction following the International Society for Heart and Lung Transplantation 2002 classification; COPD, chronic obstructive pulmonary disease; EVALI, e-cigarette- or vaping-use-associated lung injury; ILD, interstitial lung disease; IQR, interquartile range; LTRs, lung transplant recipients; PAH, pulmonary artery hypertension, RAS, restrictive allograft syndrome. One patient had typical clinical and radiological features of COVID-19 with a negative RT-PCR test, but subsequently developed positive SARS-CoV2 antibodies. † *p* < 0.05 significant.

An ICU level of care was necessary in 14 LTRs (14/59, 24%), and eight of these patients (8/14, 57%) required invasive mechanical ventilation for severe hypoxemia. No LTRs received extracorporeal membrane oxygenation support. Cell-cycle inhibitors were discontinued in all cases of LTRs requiring hospitalization.
