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Our goal was to compare the chest computed tomography (CT) imaging findings of COVID-19 in lung transplant recipients (LTR) and a group of non-transplanted controls (NTC).This retrospective study included 51 consecutive LTR hospitalized with COVID-19 from two centers. A total of 75 NTC were included for comparison. Images were classified regarding the standardized RSNA category, main pattern of lung attenuation, and longitudinal and axial distribution. Quantitative CT (QCT) analysis was performed to evaluate percentage of high attenuation areas (%HAA, threshold -250 to -700 HU). CT scoring was used to measure severity of parenchymal abnormalities.The imaging findings of COVID-19 in LTR were significantly different from controls regarding the RSNA classification and pattern of lung attenuation. LTR had a significantly higher proportion of patients with an indeterminate pattern on CT (0.31 vs. 0.11, p = 0.014). The most frequent pattern of attenuation in LTR was predominantly consolidation (0.39 vs. 0.22, p = 0.144) followed by a mixed pattern of ground-glass opacities (GGO) and consolidation (0.37 vs. 0.20, adjusted p = 0.102). On the other hand, the most common pattern in NTC was GGO predominant (0.58 vs. 0.24 of LTR, p = 0.001). LTR had significantly more severe parenchymal disease measured by CT score and %HAA by QCT (0.372 ± 0.08 vs. 0.148 ± 0.06, p0.001).The most frequent finding of COVID-19 in LTR is a predominant pattern of consolidation. Compared to NTC, LTR more frequently demonstrated an indeterminate pattern according to the RSNA classification and more extensive lung abnormalities on QCT and semi-quantitative scoring.• The most common CT finding of COVID-19 in LTR is a predominant pattern of consolidation followed by a mixed pattern of GGO and consolidation, while controls more often have a predominant pattern of GGO. • LTR more often presents with an indeterminate pattern of COVID-19 by RSNA classification than controls; therefore, molecular testing for COVID-19 is essential for LTR presenting with lower airway infection independently of imaging findings. • LTR had more extensive disease by semi-quantitative CT score and increased percentage areas of high attenuation on QCT.

Background: Mechanical ventilation during cardiothoracic surgery is life-saving, but leads to ventilator-induced diaphragm dysfunction (VIDD) and prolongs weaning from the ventilator and hospital stay. Intra-operative diaphragm electrical stimulation may preserve mitochondrial function, and thus prevent VIDD.Methods: We studied 21 patients stimulating a phrenic nerve of one hemidiaphragm every 30 min for 1min during a surgery. We collected diaphragm biopsies after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers, and protein expression and enzymatic activity of biomarkers of muscle atrophy, oxidative stress and mitophagy. Results: Patients received on average 6.2 (1.9) stimulation bouts. Stimulated hemidiaphragm showed attenuated integrative and intrinsic mitochondrial respiratory function. There were no significant differences between oxidative stress, mitophagy and atrophy protein expression levels, and mitochondrial enzyme activities.Conclusions: Intraoperative phrenic nerve electrical stimulation led to an impairment of mitochondrial respiration in the stimulated hemidiaphragm without differences in biomarkers of atrophy and oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.Trial registration: NCT03303040, Registered on the 5th of October 2017. No retrospective registration statement needed – first subject was enrolled on 2/14/2018.

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication.Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018.Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 μmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 μmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%.Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The pathogenesis of COPD is complex; however, recent studies suggest autoimmune changes, characterized by the presence of autoantibodies to elastin and collagen, may contribute to disease status. COPD patients make up approximately 30% of all lung transplants (LTx) annually, however, little is known regarding the relationship between COPD-related autoantibodies and LTx outcomes. We hypothesized that COPD patients that undergo LTx and develop primary graft dysfunction (PGD) have altered circulating autoantibody levels and phenotypic changes as compared those COPD-LTx recipients that do not develop PGD. We measured total immunoglobulin and circulating elastin and collagen autoantibody levels in a cohort of COPD lung transplant recipients pre- and post-LTx. No significant differences were seen in total, elastin, or collagen IgM, IgG, IgG1, IgG2, IgG3, and IgG4 antibodies between PGD+ and PGD- recipients. Antibody function can be greatly altered by glycosylation changes to the antibody Fc region and recent studies have reported altered IgG glycosylation profiles in COPD patients. We therefore utilized a novel mass spectrometry-based multiplexed N-glycoprotein imaging approach and measured changes in IgG-specific antibody N-glycan structures. COPD-LTx recipients who developed PGD had significantly increased IgG1 N-glycan signatures as compared PGD- recipients. In conclusion, we show that immunoglobulin and autoreactive antibody levels are not significantly different in COPD LTx recipients that develop PGD. However, using a novel IgG glycomic analysis we were able to demonstrate multiple significant increases in IgG1 specific N-glycan signatures that were predictive of PGD development. Taken together, these data represent a potential novel method for identifying COPD patients at risk for PGD development and may provide clues to mechanisms by which antibody N-glycan signatures could contribute to antibody-mediated PGD pathogenesis.

Cell lines are the mainstay in understanding the biology of COVID-19 infection, but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue allows for the in vitro study of the inter-individual heterogeneity of host response to SARS-CoV-2 infection, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 16 donors, most of whom had risk factors for severe illness from COVID-19. Cryopreserved tissues preserved 90% of cell viability and contained heterogeneous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infectible with HCoV-OC43 and SARS-CoV-2 coronavirus strains, and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL-6, CXCL8 and IFNβ in response to SARS-CoV-2 infection. Treatment of tissues with dexamethasone and the experimental drug, N-hydroxycytidine, suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted antiviral activity, suppressed viral replication in tissues from a subset of donors. In summary, we developed a novel system for the in vitro study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis.