Late-Onset Exudative Pleural Effusions Without Concomitant Airway Obstruction or Lung Parenchymal Abnormalities: A Novel Presentation of Chronic Lung Allograft Dysfunction.

Restrictive allograft syndrome (RAS) is an aggressive variant of CLAD characterized by progressive restrictive ventilatory decline and persistent pleuro-parenchymal changes that can be seen on chest CT. We identified four lung transplant recipients with a progressive restrictive ventilatory defect due to lymphocyte-predominant exudative pleural effusions, but no pleuro-parenchymal abnormalities typical of RAS. Using molecular analysis, we also found increased levels of previously described immune markers of RAS, including NFkB, 20S proteasome, lipocalin, TNFα, and TGFß, within the circulating small extracellular vesicles of the remaining living lung transplant recipient. Despite the absence of lung parenchymal changes, these patients had a poor prognosis with rapid deterioration in allograft function and no response to pleural-based interventions such as thoracentesis, decortication, and pleurodesis. We hypothesize that these cases represent a distinct CLAD phenotype characterized by progressive restriction due to pleural inflammation, lymphocyte-predominant pleural effusion, resultant compressive atelectasis, and eventual respiratory failure in the absence of lung parenchymal involvement.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

BACKGROUND: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. METHODS: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. RESULTS: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). CONCLUSION: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Prior SARS-CoV-2 infection may not alter the clinical course of COVID-19 in lung transplant recipients: A single-center experience.

BACKGROUND: In the general population, prior infection with SARS-CoV-2 reduces the risk of severe COVID-19; however, studies in lung transplant recipients (LTRs) are lacking. We sought to describe the clinical course of COVID-19 recurrence and compare outcomes between the first and second episodes of COVID-19 in LTRs. METHODS: We conducted a retrospective, single-center cohort study of LTRs with COVID-19 between January 1, 2022, and September 30, 2022, during the Omicron wave. We compared the clinical course of a second episode of COVID-19 to that of the patients' own first episode and to that of LTRs who developed a first episode during the study period. RESULTS: During the study period, we identified 24 LTRs with COVID-19 recurrence and another 75 LTRs with a first episode of COVID-19. LTRs who survived the initial episode of COVID-19 had a similar disease course with recurrence, with a trend toward reduced hospitalization (10 (41.6%) vs. 4 (16.7%), p = .114). Furthermore, compared to LTRs with a primary infection during the Omicron wave, those with a reinfection had a non-statistically significant trend toward reduced hospitalizations (aOR .391, 95% CI [.115-1.321], p = .131), shorter lengths-of-stay (median, 4 vs. 9 days, p = .181), and reduced intensive care unit admissions, intubations, and COVID-19-related mortality. CONCLUSIONS: LTRs who survive the first episode of COVID-19 are likely to have a similar clinical course with recurrent episodes. Although recurrent COVID-19 may be milder, larger, well-powered studies are needed to confirm this observation. Ongoing precautions are warranted.

Morbidity of antireflux surgery in lung transplant and matched nontransplant cohorts is comparable.

BACKGROUND: Safety data on perioperative outcomes of laparoscopic antireflux surgery (LARS) after lung transplantation (LT) are lacking. We compared the 30-day readmission rate and short-term morbidity after LARS between LT recipients and matched nontransplant (NT) controls. METHODS: Adult patients who underwent LARS between January 1, 2015, and October 31, 2021, were included. The participants were divided into two groups: LT recipients and NT controls. First, we compared 30-day readmission rates after LARS between the LT and NT cohorts. Next, we compared 30-day morbidity after LARS between the LT cohort and a 1-to-2 propensity score-matched NT cohort. RESULTS: A total of 1328 patients (55 LT recipients and 1273 NT controls) were included. The post-LARS 30-day readmission rate was higher in LT recipients than in the overall NT controls (14.5% vs. 2.8%, p < 0.001). Compared to matched NT controls, LT recipients had a lower prevalence of paraesophageal hernia, a smaller median hernia size, and higher peristaltic vigor. Also compared to the matched NT controls, the LT recipients had a lower median operative time but a longer median length of hospital stay. The proportion of patients with a post-LARS event within 30 postoperative days was comparable between the LT and matched NT cohorts (21.8% vs 14.5%, p = 0.24). CONCLUSIONS: Despite a higher perceived risk of comorbidity burden, LT recipients and matched NT controls had similar rates of post-LARS 30-day morbidity at our large-volume center with expertise in transplant and foregut surgery. LARS after LT is safe.

Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area.

BACKGROUND: Lung transplant recipients residing in the endemic region are vulnerable to severe morbidity and mortality from Coccidioides. As infection risk persists beyond the first posttransplant year, investigations evaluating extended prophylaxis durations are needed. The purpose of this study is to assess the incidence of coccidioidomycosis among lung transplant recipients receiving universal lifelong azole antifungal prophylaxis. METHODS: Patients receiving transplants from 2013-2018 and initiated on azole antifungal prophylaxis at a lung transplant center in Arizona were included and followed through 2019 or until death, second transplant, or loss to follow-up. Recipients who died or received treatment for coccidioidomycosis during the transplant admission, or who had received a previous transplant, were excluded. The primary outcome was proven or probable coccidioidomycosis with new asymptomatic seropositivity assessed secondarily. RESULTS: A total of 493 lung transplant recipients were included, with 82% initiated on itraconazole prophylaxis, 9.3% on voriconazole, and 8.5% on posaconazole. Mean age at transplant was 62 years, 77% were diabetic, and 8% were seropositive for Coccidioides pretransplant. After a median follow-up of 31 months, 1 proven infection and 1 case of new asymptomatic seropositivity (1/493 each, 0.2% incidence) occurred during the study period. The single coccidioidomycosis case occurred 5 years posttransplant in a patient who had azole prophylaxis stopped several months prior. Although within-class switches were common throughout the study period, permanent discontinuation of azole prophylaxis was rare (1.4% at end of follow-up). CONCLUSIONS: Universal lifelong azole prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients residing in endemic regions.

Novel role for tumor suppressor gene, liver kinase B1, in epithelial-mesenchymal transition leading to chronic lung allograft dysfunction.

Epithelial-mesenchymal transition (EMT) has been implicated to play a role in chronic lung allograft dysfunction (CLAD). Liver kinase B1 (LKB1), a tumor suppressor gene, can regulate EMT. However, its role in CLAD development following lung transplantation remains unknown. Using qRT-PCR, biopsies from lung transplant recipients with bronchiolitis obliterans syndrome (BOS) demonstrated significant downregulation of LKB1 (p = .0001), compared to stable biopsies. To determine the role of LKB1 in EMT development, we analyzed EMT in human bronchial epithelial cell line BEAS-2B. Knockdown of LKB1 by siRNA significantly dysregulated mesenchymal markers expression in BEAS-2B cells. Following incubation of human primary bronchial epithelial cell or BEAS-2B cells with exosomes isolated from BOS or stable lung transplant recipients, LKB1 expression was inhibited when incubated with BOS-exosome. Incubation with BOS-exosomes also decreased LKB1 expression and induced EMT markers in air-liquid interface culture method. Our results provide novel evidence that exosomes released from transplanted lungs undergoing chronic rejection are associated with inactivated tumor suppressor gene LKB1 and this loss induces EMT leading to the pathogenesis of CLAD following human lung transplantation.

Outcomes after lung transplantation in recipients aged 70 years or older.

BACKGROUND: The proportion of lung transplant (LTx) recipients older than 70 years is increasing, thus we assessed long-term survival after LTx in this cohort relative to younger counterparts. PATIENTS AND METHODS: We retrospectively reviewed charts of patients who underwent LTx between 2012 and 2016 at our center and divided patients by age: group A (<65 years), B (65-69 years), and C (≥70 years). Survival statistics were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: The study included 375 LTx recipients: 221 (58.9%) in group A, 109 (29.1%) in group B, and 45 (12.0%) in group C. Group C was mostly men (37/45 [82.2%]; P = 0.003) and had the highest mean serum creatinine at listing (P = 0.02). Survival at 1, 3, and 5 years after transplant in group A (93.2%, 70.1%, 58.8%) was significantly higher than group B (83.5%, 59.6%, 44.0%; P = 0.005, 0.028, 0.006, log-rank test) and was similar to group C (86.7%, 64.4%, 57.8%), although trended higher at 1 year (P = 0.139, 0.274, 0.489, log-rank test). Groups B and C had comparable survival at all time points. CONCLUSIONS: Although survival decreased after age 65, long-term survival was comparable between LTx recipients aged 65-69 years and recipients ≥70 years.

Exploring optimal multimode vibronic pathways in singlet fission of azaborine analogues of perylene.

The development of new singlet fission chromophores is a vibrant area of research to explore the possibility of efficient photovoltaic devices. Using high-level ab-initio density matrix renormalization group calculations, we present a systematic analysis of BN-doped perylenes for their potential application as singlet fission candidates. Four singlet fission chromophores are identified considering the monomer-based properties and their excitonic characters are further analyzed in a dimer configuration optimized in a six-dimensional space for local maxima of fission rates. Furthermore, a multistate multimode vibronic Hamiltonian is employed to identify intra- and interstate vibrational pathways for excitation energy modulation. Several photophysical properties such as Davydov splitting, activation energy and vibronic admixture of multiexcitonic and charge-transfer states are calculated for physically accessible dimers. The optimal dimer packing results in appropriate vibrational relaxation of singlet fission states and promotes significant population transfer which would be more attenuated without such couplings. This work not only identifies potential singlet fission systems with favorable electronic properties but also highlights the sensitivity of dimer packings with respect to the substitution patterns in singlet fission chromophores.

Nocardia prophylaxis, treatment, and outcomes of infection in lung transplant recipients: A matched case-control study.

BACKGROUND: Lung transplant recipients are at heightened risk for nocardiosis compared to other solid organ transplant recipients, with incidence rates as high as 9% and up to 30% associated mortality. No controlled studies assessing risk factors for nocardiosis in this high-risk population have been reported. METHODS: Patients undergoing lung transplantation at a single center between 2012 and 2018 and diagnosed with nocardiosis post-transplant were matched 1:2 to uninfected control subjects on the basis of age, transplant date, and sex. RESULTS: The incidence of nocardiosis in this lung transplant population was 3.4% (20/586), occurring a median of 9.4 months (range 4.4-55.2) post-transplant. In multivariable analysis, consistent use of trimethoprim/sulfamethoxazole (TMP/SMX) in the 12 weeks prior to diagnosis was independently associated with protection against nocardiosis (OR 0.038; 95% CI 0.01-0.29; P = .002). Augmented immunosuppression in the 6 months prior to diagnosis was independently associated with the development of nocardiosis (OR 9.94; 95% CI 1.62- 61.00; P = .013). Six case patients (30%) had disseminated disease; all-cause 6-month mortality was 25%. The most common species was Nocardia farcinica (7/17 isolates), which was associated with dissemination and mortality. The most active antibiotics were TMP/SMX (100%), linezolid (100%), and amikacin (76%). Imipenem was only active against 4/17 isolates (24% susceptibility), with two isolates becoming non-susceptible later in therapy. CONCLUSIONS: Trimethoprim/sulfamethoxazole prophylaxis was shown to be protective against nocardiosis in lung transplant recipients, while augmented immunosuppression conferred increased risk. Institutional epidemiologic data are needed to best guide empiric therapy for Nocardia, as historical in vitro data may not predict local susceptibilities.

COVID-19 in a lung transplant recipient: Exploring the diagnostic role of circulating exosomes and the clinical impact of advanced immunosuppression.

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor-derived lung self-antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76-year-old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti-thymocyte globulin, who subsequently contracted SARS-CoV-2 and developed a sharp increase in the mean fluorescent intensity of anti-HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS-CoV-2 infection, revealed the presence of lung self-antigens and HLA class II molecules. After the patient contracted SARS-CoV-2, exosomes with the SARS-CoV-2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS-CoV-2 spike protein were no longer detected; however, exosomes with lung self-antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens.

Factors associated with skin cancer in lung transplant recipients: A single-center experience.

BACKGROUND: Skin cancer is common after solid organ transplantation, but few have investigated it after lung transplant (LTx). OBJECTIVE: We assessed incidence and predictors of non-melanoma skin cancer (NMSC) post-LTx. METHODS: We studied patients who underwent LTx at our center from 2012 to 2015. RESULTS: Of 287 patients, mean age was 59.6 ± 11 years, 170 (59.2%) were men, and 231 (80.5%) were white. Seventy-six (26.5%) developed NMSC over a median follow-up of 32 months (IQR, 23-45). Of those with NMSC, 37% developed subsequent skin cancer of the same type. Independent predictors of decreased odds of NMSC and squamous cell carcinoma (SCC) were non-white race (P = .002; P = .003) and body mass index >30 kg/m2 compared with underweight patients (P = .001, P = .009). Patients with skin cancer pre-LTx had higher risk of post-LTx skin cancer (P = .02). Voriconazole use ≥100 days was associated with increased risk of SCC (P = .03), but not increased risk of basal cell carcinoma. Out of 76, 4 (5.3%) died from skin cancer. LIMITATIONS: Retrospective, single-center study. CONCLUSION: Squamous cell carcinoma risk post-LTx may increase with prolonged voriconazole use in white patients with pre-LTx history of skin cancer, whereas excess body weight may be protective from NMSC. Regular pre- and post-LTx skin cancer screenings and guidelines are warranted.

Hydroalkylation of styrenes enabled by boryl radical mediated halogen atom transfer.

In this study, we present an inexpensive, stable, and easily available boryl radical source (BPh4Na) employed in a Halogen Atom Transfer (XAT) methodology. This mild and convenient strategy unlocks the use of not only alkyl iodides as radical precursors but also of the more challenging alkyl and aryl bromides to generate C-centered radicals. The generated radicals were further engaged in the anti-Markovnikov hydroalkylation of electronically diverse styrenes, therefore achieving the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. A series of experimental and computational studies revealed the prominent role of BPh4Na in the halogen abstraction step.

Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience.

Introduction: Remdesivir (REM) and molnupiravir (MOL) are commonly used to treat lung transplant recipients (LTRs) with COVID-19; however, the clinical efficacy of these medications is yet to be compared. In this retrospective cohort study, we compared the clinical outcomes between LTRs with mild-to-moderate COVID-19 treated with REM and those treated with MOL. Methods and Results: Between March 2020 and August 2022, 195 LTRs developed COVID-19 at our center. After excluding 82 who presented with severe disease requiring hospitalization, the remaining 113 were included in the analysis: 54 did not receive antiviral treatment, 30 were treated with REM, and 29 were treated with MOL. Adjusted multivariable logistic regression analysis showed similar rates of hospitalization (adjusted odds ratio (aOR) 1.169, [95% confidence interval (95% CI) 0.105-12.997, p = 0.899], ICU admission (aOR 0.822, 95% CI 0.042-16.220, p = 0.898), mechanical ventilation (aOR 0.903, 95% CI 0.015-55.124, p = 0.961), and COVID-19-related mortality (aOR 0.822, 95% CI 0.042-16.220, p = 0.898) between LTRs treated with REM and those treated with MOL for mild-to-moderate COVID-19, irrespective of SARS-CoV-2 strain. Conclusion: MOL may be a suitable alternative to REM to treat LTRs with mild-to-moderate COVID-19, and the choice of antiviral therapy can be driven by practical considerations such as route of administration and drug availability.

The crucial role of stability of intercalating agent for DNA binding studies in DMSO/water system.

In recent years, extensive research has been directed towards understanding the interactions between various zinc complexes with DNA, specifically delving into their intercalation and binding behaviors. The binding of zinc complexes to DNA is particularly intriguing due to their distinctive intercalating capabilities. This study unveils a remarkable phenomenon observed with a specific Zn complex, ([B-Zn-N3], where B is a Schiff base ligand), during DNA intercalation investigations in the popular DMSO-Water binary solvent mixture. An unanticipated observation revealed time-dependent changes in the UV-visible absorption spectroscopic studies, coupled with the existence of an isosbestic point. This observation questions the stability of the intercalating agent itself during the intercalation process. The emergence of a decomposed product during the intercalation study has been confirmed through various analytical techniques, including CHN analysis, MALDI mass, XPS, Raman spectroscopy, and Powder XRD. The change in the chemical species on intercalation is further substantiated by theoretical studies, adding depth to our understanding of the intricate dynamics at play during DNA intercalation with the [B-Zn-N3] complex in the DMSO-Water system.

Shining light on tryptamine-derived isocyanides: access to constrained spirocylic scaffolds.

Dearomatization of indoles through a charge transfer complex constitutes a powerful tool for synthesizing three-dimensional constrained structures. However, the implementation of this strategy for the dearomatization of tryptamine-derived isocyanides to generate spirocyclic scaffolds remains underdeveloped. In this work, we have demonstrated the ability of tryptamine-derived isocyanides to form aggregates at higher concentration, enabling a single electron transfer step to generate carbon-based-radical intermediates. Optical, HRMS and computational studies have elucidated key aspects associated with the photophysical properties of tryptamine-derived isocyanides. The developed protocol is operationally simple, robust and demonstrates a novel approach to generate conformationally constrained spirocyclic scaffolds, compounds with high demand in various fields, including drug discovery.

Evolving impact of the COVID-19 pandemic on lung transplant recipients: A single-center experience.

BACKGROUND: Lung transplant recipients (LTRs) are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19); however, the disease course has changed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have mutated. We compared COVID-19-related clinical outcomes in LTRs at different stages of the pandemic. We also identified risk factors for developing severe COVID-19 independent of the dominant SARS-CoV-2 variant. METHODS: This single-center, retrospective cohort study of LTRs with COVID-19 used Cox regression analyses and bootstrapping to identify factors affecting COVID-19 severity. RESULTS: Between March 2020 and August 2022, 195 LTRs were diagnosed with COVID-19, almost half (89 [45.6%]) during the Omicron period. A total of 113 (58.5%) LTRs were hospitalized and 47 (24.1%) died. Age >65 years increased the risk of hospitalization and death. Although infection with the Omicron variant was associated with a lower risk of hospitalization, the median length of hospital stay (10 days, [interquartile range, 5-19]) was similar between the variants. Intensive care unit (ICU) admission and death were more common with the Delta variant but comparable between the original, Alpha, and Omicron variants. Remdesivir and molnupiravir reduced the risk of hospitalization, and monoclonal antibody therapy reduced the risk of ICU admission, intubation, and death. Vaccination and pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab did not significantly reduce COVID-19-related ICU admission, intubation, or mortality among LTRs. CONCLUSIONS: LTRs with COVID-19 continue to have high hospitalization rates and prolonged hospital stays, despite the reduced virulence of the Omicron variant. More effective PrEP and therapeutic interventions for COVID-19 among vulnerable patient groups are needed.

Efficient, narrow-band, and stable electroluminescence from organoboron-nitrogen-carbonyl emitter.

Organic light-emitting diodes (OLEDs) exploiting simple binary emissive layers (EMLs) blending only emitters and hosts have natural advantages in low-cost commercialization. However, previously reported OLEDs based on binary EMLs hardly simultaneously achieved desired comprehensive performances, e.g., high efficiency, low efficiency roll-off, narrow emission bands, and high operation stability. Here, we report a molecular-design strategy. Such a strategy leads to a fast reverse intersystem crossing rate in our designed emitter h-BNCO-1 of 1.79×105 s-1. An OLED exploiting a binary EML with h-BNCO-1 achieves ultrapure emission, a maximum external quantum efficiency of over 40% and a mild roll-off of 14% at 1000 cd·m-2. Moreover, h-BNCO-1 also exhibits promising operational stability in an alternative OLED exploiting a compact binary EML (the lifetime reaching 95% of the initial luminance at 1000 cd m-2 is ~ 137 h). Here, our work has thus provided a molecular-design strategy for OLEDs with promising comprehensive performance.

Cell-type-specific and disease-associated expression quantitative trait loci in the human lung.

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects. Furthermore, we identified disease interaction eQTLs and demonstrated that this class of associations is more likely to be cell-type-specific and linked to cellular dysregulation in pulmonary fibrosis. Finally, we connected lung disease risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression and implicates context-specific eQTLs as key regulators of lung homeostasis and disease.

Pre-exposure Prophylaxis with Tixagevimab-cilgavimab did not Reduce Severity of COVID-19 in Lung Transplant Recipients with Breakthrough Infection.

Lung transplant recipients (LTRs) have an increased risk of COVID-19-related morbidity and mortality. Tixagevimab-cilgavimab (tix-cil) is a long-acting monoclonal antibody combination granted Emergency Use Authorization approval by the US Food and Drug Administration for COVID-19 pre-exposure prophylaxis (PrEP) in immunocompromised patients. We sought to determine whether tix-cil 300-300 mg reduced the incidence and disease severity of severe acute respiratory syndrome coronavirus 2 infection in LTRs during the Omicron wave. Methods: We performed a retrospective, single-center cohort study of LTRs who had received a COVID-19 diagnosis between December 2021 and August 2022. We compared baseline characteristics and clinical outcomes after COVID-19 between LTRs who received tix-cil PrEP and those who did not. We then conducted propensity-score matching based on baseline characteristics and therapeutic interventions and compared clinical outcomes between the 2 groups. Results: Of 203 LTRs who received tix-cil PrEP and 343 who did not, 24 (11.8%) and 57 (16.6%), respectively, developed symptomatic COVID-19 (hazard ratio [HR], 0.669; 95% confidence interval [CI], 0.415-1.079; P = 0.099). The hospitalization rate of LTRs with COVID-19 during the Omicron wave trended lower in the tix-cil group than in the non-tix-cil group (20.8% versus 43.1%; HR, 0.430; 95% CI, 0.165-1.118; P = 0.083). In propensity-matched analyses, 17 LTRs who received tix-cil and 17 LTRs who did not had similar rates of hospitalization (HR, 0.468; 95% CI, 0.156-1.402; P = 0.175), intensive care unit admission (HR, 3.096; 95% CI, 0.322-29.771; P = 0.328), mechanical ventilation (HR, 1.958; 95% CI, 0.177-21.596; P = 0.583), and survival (HR, 1.015; 95% CI, 0.143-7.209; P = 0.988). COVID-19-related mortality was high in both propensity-score-matched groups (11.8%). Conclusions: Breakthrough COVID-19 was common among LTRs despite tix-cil PrEP, possibly due to reduced efficacy of monoclonal antibodies against the Omicron variant. Tix-cil PrEP may reduce the incidence of COVID-19 in LTRs, but it did not reduce disease severity during the Omicron wave.