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.

Well-being of Cardiothoracic Surgeons in the Time of COVID-19: A Survey by the Wellness Committee of the American Association for Thoracic Surgery.

The prevalence of burnout among physicians has been increasing over the last decade, but data on burnout in the specialty of cardiothoracic surgery are lacking. We aimed to study this topic through a well-being survey. A 54-question well-being survey was developed by the Wellness Committee of the American Association for Thoracic Surgery (AATS) and sent by email from January through March of 2021 to AATS members and participants of the 2021 annual meeting. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by Chi-square tests or independent samples t-tests, as appropriate. The results from 871 respondents (17% women) were analyzed. Many respondents reported at least moderately experiencing: 1) a sense of dread coming to work (50%), 2) physical exhaustion at work (58%), 3) a lack of enthusiasm at work (46%), and 4) emotional exhaustion at work (50%). Most respondents (70%) felt that burnout affected their personal relationships at least "some of the time," and many (43%) experienced a great deal of work-related stress. Importantly, most respondents (62%) reported little to no access to workplace resources for emotional support, but those who reported access reported less burnout. Most respondents (57%) felt that the COVID-19 pandemic has negatively affected their well-being. On a positive note, 80% felt their career was fulfilling and enjoyed their day-to-day job at least "most of the time." Cardiothoracic surgeons experience high levels of burnout, similar to that of other medical professionals. Interventions aimed at mitigating burnout in this profession are discussed.

Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes severe acute respiratory syndrome. mRNA vaccines directed at the SARS-CoV-2 spike protein resulted in development of Abs and protective immunity. To determine the mechanism, we analyzed the kinetics of induction of circulating exosomes with SARS-CoV-2 spike protein and Ab following vaccination of healthy individuals. Results demonstrated induction of circulating exosomes expressing spike protein on day 14 after vaccination followed by Abs 14 d after the second dose. Exosomes with spike protein, Abs to SARS-CoV-2 spike, and T cells secreting IFN-γ and TNF-α increased following the booster dose. Transmission electron microscopy of exosomes also demonstrated spike protein Ags on their surface. Exosomes with spike protein and Abs decreased in parallel after four months. These results demonstrate an important role of circulating exosomes with spike protein for effective immunization following mRNA-based vaccination. This is further documented by induction of humoral and cellular immune responses in mice immunized with exosomes carrying spike protein.

Respiratory viral infection in lung transplantation induces exosomes that trigger chronic rejection.

BACKGROUND: Respiratory viral infections can increase the risk of chronic lung allograft dysfunction after lung transplantation, but the mechanisms are unknown. In this study, we determined whether symptomatic respiratory viral infections after lung transplantation induce circulating exosomes that contain lung-associated self-antigens and assessed whether these exosomes activate immune responses to self-antigens. METHODS: Serum samples were collected from lung transplant recipients with symptomatic lower- and upper-tract respiratory viral infections and from non-symptomatic stable recipients. Exosomes were isolated via ultracentrifugation; purity was determined using sucrose cushion; and presence of lung self-antigens, 20S proteasome, and viral antigens for rhinovirus, coronavirus, and respiratory syncytial virus were determined using immunoblot. Mice were immunized with circulating exosomes from each group and resulting differential immune responses and lung histology were analyzed. RESULTS: Exosomes containing self-antigens, 20S proteasome, and viral antigens were detected at significantly higher levels (p < 0.05) in serum of recipients with symptomatic respiratory viral infections (n = 35) as compared with stable controls (n = 32). Mice immunized with exosomes from recipients with respiratory viral infections developed immune responses to self-antigens, fibrosis, small airway occlusion, and significant cellular infiltration; mice immunized with exosomes from controls did not (p < 0.05). CONCLUSIONS: Circulating exosomes isolated from lung transplant recipients diagnosed with respiratory viral infections contained lung self-antigens, viral antigens, and 20S proteasome and elicited immune responses to lung self-antigens that resulted in development of chronic lung allograft dysfunction in immunized mice.