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European Respiratory Journal Conference: European Respiratory Society International Congress, ERS ; 60(Supplement 66), 2022.
Article in English | EMBASE | ID: covidwho-2285029


The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.

The Journal of Heart and Lung Transplantation ; 40(4, Supplement):S143-S144, 2021.
Article in English | ScienceDirect | ID: covidwho-1141792


Purpose The respiratory system, and namely the lung, is undoubtedly the preferential target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical pictures are extremely various, up to the intensive care unit (ICU) admission for acute respiratory distress syndrome (ARDS). Lung transplantation (LT) is a consolidate therapeutic option for end-stage chronic respiratory diseases. Its role in an acute setting is questionable, particularly due to lack of experiences, donor shortage, and the difficulty to fully evaluate the potential recipient. We report our preliminary experience with the first two cases of LT for SARS-CoV-2 related ARDS, trying to provide some food for thought. Methods We retrospectively analysed our first two cases of bilateral LT for ARDS after COVID-19. We recorded data on pre-transplantation clinical course, transplantation management and outcomes. Results The two patients had a similar clinical evolution of COVID-19. Transplantations were successful in both cases;the first patient is alive and in good condition 5 months after transplantation, while the second died 62 days after surgery. Table 1 shows clinical details and relevant time-points. Conclusion Our experience showed that LT for COVID-19 is feasible. Importantly, observing a dedicated protocol made the procedure safe for the healthcare staff involved. On the other hand, our second unsuccessful case poses relevant questions: first of all, lung transplantation should be reserved to highly selected patient, after careful clinical, infective as well 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.