key: cord-0844336-blxer36d authors: Domjan, Matic; Harlander, Matevž; Knafelj, Rihard; Ribarič, Suada Fileković; Globokar, Mojca Drnovšek; Gorjup, Vojka; Štupnik, Tomaž title: Lung transplantation for end-stage respiratory failure following severe COVID-19: a report of two cases date: 2021-08-28 journal: Transplant Proc DOI: 10.1016/j.transproceed.2021.08.029 sha: be707c9cf4f5a1efb8c4d203280ecd2f67c06284 doc_id: 844336 cord_uid: blxer36d We report two cases of bilateral lung transplantation (LTx) for non-resolving COVID-19 associated respiratory failure. In the first patient, the SARS CoV-2 infection caused acute respiratory distress syndrome (ARDS) requiring prolonged ECMO support, while in the second patient, COVID-19 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The two cases represent the two ends of the spectrum showing significant differences in preoperative and postoperative courses. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Lung transplantation for end-stage respiratory failure following severe COVID-19: a report of two cases (3) (4) (5) . Experiences are limited, and data on patient selection, postoperative care, and outcomes remain scarce. Case report Case 1 In December 2020, a successful LTx was performed in a 34-year-old male patient with COVID-19 associated ARDS without significant comorbidities. Mechanical ventilation was required for 11 days, followed by extracorporeal membranous oxygenation (ECMO) suppofor 27 days without any clinical or radiological improvement. The patient was then listed for LTx. He was deeply sedated by utilizing a maximum dose of sevoflurane, dexmedetomidine, midazolam, fentanyl, and neuromuscular blockers because every attempt to reduce sedation resulted in agitation and clinical deterioration. The patient was, therefore, unable to discuss treatment options and consent to LTx. A size reduced (without the middle lobe and lingula) donor lung of predicted total lung capacity (pTLC) of 7.7L was transplanted to this patient with a pTLC of 7.3L. ECMO was successfully removed in the operating room, but due to ventilatory problems (low tidal volumes and elevated pCO 2 ) following approximation of the ribs, the definitive chest closure was delayed for two days. The patient was weaned from mechanical ventilation on a postoperative day (POD) 120, transferred to the medical ward on POD 138, and discharged home on POD 178 . During this long postoperative course, he also became severely depressed and received psychiatric evaluation and treatment. Case 2 In February 2021, a second successful LTx was performed in a previously healthy 53-year-old male with respiratory failure for irreversible post-COVID-19 pulmonary fibrosis. The patient was listed for LTx after 57 days of mechanical ventilation without any clinical and radiological improvement. In addition to pressure-controlled ventilation with high oxygen concentration, inhaled nitric oxygen (iNO) was also administered, but ECMO support was not needed. The patient did not require any sedation and was undergoing physiotherapy while being mechanically ventilated. He was also able to discuss treatment options and consent to LTx. An entire right lung and a left upper lobe of a donor lung with pTLC of 7.3L were transplanted to this patient with pTLC of 7.0L. The patient was weaned from mechanical ventilation on POD 13, transferred to the medical ward on POD 23, and discharged home on POD 52. Even though both patients received LTx for severe respiratory failure following COVID-19 pneumonia, their condition differed significantly, resulting in two completely different postoperative pathways. 1. The COVID-19 ARDS patient required deep sedation with ECMO support and later underwent LTx without first-person consent, resulting in an extremely prolonged hospital stay. 2. The post-COVID-19 pulmonary fibrosis patient was, on the other hand, fully conscious and ambulatory, albeit mechanically ventilated, and recovered very rapidly after LTx. Data on ECMO bridge to transplantation from large volume centers show improved outcomes in awake patients who managed to undergo physiotherapy and become ambulatory (6) . In our two cases, the pretransplant rehabilitation significantly improved outcomes and speeded up weaning from mechanical ventilation. When facing the challenge of lung transplantation in COVID-19 patients, the selection criteria are critical and may require some adjustments from the ones proposed by Cypel and Keshavjee (7).  Many patients with COVID-19 related ARDS require deep sedation to reduce oxygen consumption and breathing overdrive. Thus, discussing LTx with the patient may often be hindered (8, 9) and was possibly the main factor to trigger depression in our first patient, which was only worsened by the loss of his two other family members due to COVID-19. Considering that depression and anxiety are risk factors for morbidity and mortality after organ transplantation (10), every step should be taken to ensure first-person consent and help the patient accept a life with a transplanted organ and life-long immunosuppression. Nonetheless, as our experience indicates, when it comes to severe ARDS that require urgent life-saving lung transplantation, this may not always be possible.  We also believe that the upper age limit should not exceed 55 years for several reasons. The median age of patients not recovering from ECMO support for COVID-19 ARDS in a cohort of patients from Schmidt et al. (8) was 52 years with an interquartile range of 48-58 years. Given the increased risk for a severe course of COVID-19 in the population above 55 years (11), the 55-65 age group may easily exceed the limited LTx capacity and incapacitate centers to transplant younger and more promising candidates and patients with other indications. Moreover, recipient age is a predictor of postoperative mortality after ECMO bridging (12) . This work complied with the Decalration of Helsinki. In conclusion, lung transplantation should remain primarily a therapy for end-stage chronic pulmonary disease, although it could occasionally be used to treat ARDS. A broader international consensus should be sought to simplify decision-making and avoid possible ethical concerns, especially during a pandemic. in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg. 2015;149(1):291-6. Lung transplantation for COVID-19-associated acute respiratory distress syndrome in a PCR-positive patient Lung transplantation for patients with severe COVID-19 Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries. The Lancet Respiratory Medicine Lung Transplantation for Severe Post-Coronavirus Disease 2019 Respiratory Failure Cypel performs first double lung transplant on COVID-19 patient in Canada Extracorporeal life support as a bridge to lung transplantation-experience of a high-volume transplant center When to consider lung transplantation for COVID-19. The Lancet Respiratory Medicine Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. The Lancet Respiratory Medicine Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan Depression and Anxiety as Risk Factors for Morbidity and Mortality After Organ Transplantation: A Systematic Review and Meta-Analysis Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy