key: cord-0931807-tnngl8wc
authors: Vaira, V.; Croci, G.; Palleschi, A.; Rosso, L.; Trabattoni, D.; Biasin, M.; Morlacchi, L. C.; Rossetti, V.; Blasi, F.; Nosotti, M.; Clerici, M.; Ferrero, S.
title: Lung Allograft Dysfunction in a COVID-19 Transplanted Patient is Associated with a Peculiar Immunopathological Phenotype
date: 2021-04-30
journal: The Journal of Heart and Lung Transplantation
DOI: 10.1016/j.healun.2021.01.443
sha: c97af32225b4760c848c8b39e2f7ab6aa08b0be2
doc_id: 931807
cord_uid: tnngl8wc

Purpose Lung transplantation (LT) after severe SARS-CoV-2 infection is emerging as a life-saving medical procedure for selected patients who experience acute respiratory distress syndrome (ARDS). We present the first immunopathological evaluation of a lung allograft rejection in a patient who underwent LT because of irreversible ARDS related to COVID-19. Methods Two male patients with irreversible ARDS caused by COVID-19 underwent bilateral LT at our Institution. A surveillance transbronchial biopsy (TBB) was performed 2 months after LT in the first patient (Pt#1), while the second patient (Pt#2) died because of allograft rejection at day 62 post LT and explanted lungs were retrieved. CT imaging of the lungs was performed three days before death. Morphological examination was performed by H&E, whereas the immunophenotyping was performed by immunohistochemistry. Results Imaging and morphological examination of Pt#2 lungs indicated the presence of a graft dysfunction with features of a restrictive, widespread usual interstitial pneumonia-like syndrome (Fig. 1A, B). The immunophenotyping showed that B-lymphocytes (CD20-positive) were nearly absent, CD8-T-cells were not particularly expanded (mean positive cells within the lung stroma=13.8%; Fig. 1C), and the CD4/CD8 ratio was not decreased (Fig. 1D). The T-regs (Foxp3-positive) were 6% of the overall population (Fig. 1E). Analysis of the immune checkpoint molecules PD1, Tigit, CTLA4 and PDL1 showed that the expression of PD-L1 alone was highly increased in vases and in alveolar cells of rejected lungs, whereas it was nearly undetectable in the TBB from Pt#1 (Fig. 1F, G). Conclusion PDL1 expression in vases was previously documented as a sign of indirect ARDS. Together with our preliminary data, we can hypothesize that PDL1 may play a role in tissue effacement and graft failure, possibly indicating poor allograft prognosis.

as psychiatric evaluation. The ethical aspects should also be considered in this situation, with regard to the centre rate mortality on waiting list. Anyway, the potential role of LT in the acute and sub-acute/chronic settings suggests the need for maintaining LT centre active during pandemic. Finally, COVID-19, once more, imposes to share clinical experiences. Purpose: Lung transplantation (LT) after severe SARS-CoV-2 infection is emerging as a life-saving medical procedure for selected patients who experience acute respiratory distress syndrome (ARDS). We present the first immunopathological evaluation of a lung allograft rejection in a patient who underwent LT because of irreversible ARDS related to COVID-19. Methods: Two male patients with irreversible ARDS caused by COVID-19 underwent bilateral LT at our Institution. A surveillance transbronchial biopsy (TBB) was performed 2 months after LT in the first patient (Pt#1), while the second patient (Pt#2) died because of allograft rejection at day 62 post LT and explanted lungs were retrieved. CT imaging of the lungs was performed three days before death. Morphological examination was performed by H&E, whereas the immunophenotyping was performed by immunohistochemistry.

Results: Imaging and morphological examination of Pt#2 lungs indicated the presence of a graft dysfunction with features of a restrictive, widespread usual interstitial pneumonia-like syndrome (Fig. 1A, B) . The immunophenotyping showed that B-lymphocytes (CD20-positive) were nearly absent, CD8-T-cells were not particularly expanded (mean positive cells within the lung stroma=13.8%; Fig. 1C ), and the CD4/CD8 ratio was not decreased (Fig. 1D) . The T-regs (Foxp3-positive) were 6% of the overall population (Fig. 1E) . Analysis of the immune checkpoint molecules PD1, Tigit, CTLA4 and PDL1 showed that the expression of PD-L1 alone was highly increased in vases and in alveolar cells of rejected lungs, whereas it was nearly undetectable in the TBB from Pt#1 (Fig. 1F, G) . Conclusion: PDL1 expression in vases was previously documented as a sign of indirect ARDS. Together with our preliminary data, we can hypothesize that PDL1 may play a role in tissue effacement and graft failure, possibly indicating poor allograft prognosis. Purpose: Clinical characteristics of SARS-CoV-2 infection and virus-specific humoral and cellular response were analyzed in 4 heart (HR) and 3 lung (LR) Tx recipients in standard triple immunosuppressive regimen.

Methods: SARS-CoV-2 infection was diagnosed by real-time PCR on nasopharingeal swabs (NPS). T-cell response to structural antigens Spike (S), Envelope (E), Membrane (M) and Nucleocapsid (N) was evaluated by PBMC stimulation with overlapping peptides spanning the entire viral proteins and subsequent detection of cell activation markers CD137 and CD25. Serum IgG antibody to S and N, and IgA antibody to S were determined by ELISA. Results: Three patients developed SARS-CoV-2 infection early (<3 months) and four patients late (>3 years) after Tx. One HR was asymptomatic, one LR presented only gastrointestinal symptoms, and five patients developed dyspnea with radiologic signs of interstitial pneumonia (in one HR ICU admittance was necessary. All patients recovered from SARS-CoV-2 infection, with viral clearance from NPS within 3 weeks. However, two HR (one early and one late HR) died at 6 and 4 months after infection because of multi-organ failure and sudden death. Both deaths were considered as unrelated to SARS-CoV2 infection. Patients who had no lung involvement did not develop specific antibody response, while all the other five patients developed IgG and IgA antibodies to S, and IgG antibody to N, within 2 months after infection. All the symptomatic patients developed a detectable CD4+ T-cell response to two or more antigens. Four patients were subsequently examined >3 months after infection, showing the persistence of IgG and IgA antibodies to S and a decline of IgG antibody to N, while CD4+ T-cell response to N was maintained. Timing of Tx did not affect the occurrence of virus specific immunity. Conclusion: Although this series is small, the data indicate that immunosuppression does not prevent the development of a specific humoral and cellular anti-SARS-CoV-2 response, more likely in patients who have experienced clinically relevant pneumonia. These preliminary data encourage the maintenance of regular follow-up to monitor the persistence of immune response and the potential occurrence of SARS-CoV-2-related sequelae in heart and lung recipients.

Purpose: From March 17 th to April 29 th , our ECMO Program placed 30 adult patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) for management of coronavirus disease 2019 (COVID-19). This acute increase in volume placed a strain on our available ECMO-competent nursing staff. Although perfusionists function as our ECMO specialists, our critical care nurses provide continuous circuit monitoring and respond to emergencies. Because of the need to increase the number of ECMO-competent nurses

Results: From March 27 th to May 4 th , 145 nurses completed training, increasing our total number of ECMO-competent nurses from 126 to 271 (115% increase). From March 17 th to June 30 th , 20,677 ECMO care hours were provided. Pre-training, all 634 care hours were 100% provided by Group A nurses

At the conclusion of the surge, 28 out of 30 (93%) patients survived ECMO and 26 out of 29 patients (90%) survived to hospital discharge. One patient has a pending hospital disposition. Conclusion: Rapid implementation of an abbreviated ECMO education program for nurses is feasible