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.

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.

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.

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.

Hospitalized patients with irreversible lung injury from COVID-19 have higher morbidity but similar 1-year survival after lung transplant compared to hospitalized patients transplanted for restrictive lung disease.

BACKGROUND: Hospitalized lung transplant (LT) recipients (LTRs) have higher post-LT morbidity and mortality than those who are well enough to wait for transplant at home. Outcomes after LT for COVID-19-associated acute respiratory distress syndrome (CARDS) may be even worse; thus, we compared post-LT outcomes between hospitalized LTRs transplanted for CARDS and those transplanted for restrictive lung disease (RLD). METHODS: Between 2014 and 2021, hospitalized LTRs ≥18 years old with CARDS or RLD were included. Primary and secondary outcomes were 1-year post-LT survival and postoperative morbidity. For each patient in the CARDS group, an analysis of 1-to-1 matched patients from the RLD group was performed using logistic regression modeling. RESULTS: Of 764 LTRs, 163 (21.3%) were hospitalized at the time of LT; 132 met the inclusion criteria: 11 (8.3%) were transplanted for CARDS and 121 (91.7%) for RLD. LTRs with CARDS were younger with longer pre-LT hospitalization stays and higher rates of pretransplant mechanical ventilation, dialysis, and ECMO as a bridge to transplant. A propensity-matched analysis demonstrated comparable rates of intrathoracic adhesions, posttransplant duration of mechanical ventilation, PGD3 at 72 hours, and delayed chest closure. Compared to LTRs with RLD, those with CARDS had significantly longer posttransplant hospital stays and a higher prevalence of ACR ≥A2 and DSA >2000 MFI, but comparable 1-year survival rates. CONCLUSION: Even with careful selection, LT for patients with CARDS was associated with significant morbidity; however, 1-year survival of recipients with CARDS was comparable to that of matched hospitalized recipients with RLD.

Inpatient Lung Transplant Evaluation Is Associated With Increased Risk of Morbidity, Mortality, and Cost of Care After Transplant.

Lung transplantation is an important option for patients with end-stage lung disease. Many of these patients deteriorate rapidly and require inpatient care at the time of the transplant evaluation. RESEARCH QUESTION: How does the setting of lung transplant evaluation relate to perioperative outcomes, short-term postoperative outcomes, and healthcare costs accrued after transplant? DESIGN: We reviewed the records of patients who underwent primary, bilateral lung transplantation at our center between January 1, 2014 and May 31, 2016. Patient evaluation setting was categorized as inpatient, outpatient, or combined. Demographics, clinical characteristics, and cost of care were assessed. RESULTS: The study included 207 patients: 40 (19.3%) evaluated as inpatients, 146 (70.5%) as outpatients, and 21 (10.1%) as combined. Inpatients had the highest mean lung allocation scores (71.2 vs 49.7 [combined] and 40.8 [outpatient]; P < 0.001), lowest functional status at listing (P < 0.001), highest number of blood products used during surgery (P < 0.001), highest incidence of re-exploration for bleeding (P = 0.006), and longest posttransplant hospital stays (median, 35 vs 15 days [combined] and 12 days [outpatient]; P < 0.001). One-year survival trended lower for inpatients (log-rank, P = 0.056). Inpatient evaluations had the highest total, variable, and fixed costs of posttransplant care (P < 0.001). CONCLUSION: Inpatient lung transplant evaluation was associated with longer hospital stays, higher perioperative morbidity, and lower 1-year survival. Partial or complete inpatient evaluation was associated with a higher cost of care posttransplant.