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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., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The post-operative management of a lung transplant recipient can be complex. Several factors including medical comorbidities, severity of illness at the time of transplant and intra-operative events can affect graft function and overall survival. During the immediate post-operative period, it becomes essential for early recognition of disease-specific sequelae as they can impact the patient's outcome and quality of life. This often necessitates a multidisciplinary team of pulmonologists, surgeons, medical sub-specialists as well as skilled nurses and respiratory therapists familiar with caring for these patients. Based on the experiences of a high-volume transplant center, this chapter will outline key considerations within each organ system in this specific patient population in the Intensive Care Unit., Competing Interests: Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-1441). The series “Lung Transplantation: Past, Present, and Future” was commissioned by the editorial office without any funding or sponsorship. The author has no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Tuberculosis remains a leading cause of death worldwide, despite the availability of effective chemotherapy and a vaccine. Bacillus Calmette-Guérin (BCG), the tuberculosis vaccine, is an attenuated mutant of Mycobacterium bovis that was isolated after serial subcultures, yet the functional basis for this attenuation has never been elucidated. A single region (RD1), which is absent in all BCG substrains, was deleted from virulent M. bovis and Mycobacterium tuberculosis strains, and the resulting DeltaRD1 mutants were significantly attenuated for virulence in both immunocompromised and immunocompetent mice. The M. tuberculosis DeltaRD1 mutants were also shown to protect mice against aerosol challenge, in a similar manner to BCG. Interestingly, the DeltaRD1 mutants failed to cause cytolysis of pneumocytes, a phenotype that had been previously used to distinguish virulent M. tuberculosis from BCG. A specific transposon mutation, which disrupts the Rv3874 Rv3875 (cfp-10 esat-6) operon of RD1, also caused loss of the cytolytic phenotype in both pneumocytes and macrophages. This mutation resulted in the attenuation of virulence in mice, as the result of reduced tissue invasiveness. Moreover, specific deletion of each transcriptional unit of RD1 revealed that three independent transcriptional units are required for virulence, two of which are involved in the secretion of ESAT-6 (6-kDa early secretory antigenic target). We conclude that the primary attenuating mechanism of bacillus Calmette-Guérin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness.