key: cord-0703187-azq82peq authors: Umberto, Maggi; Luciano, De Carlis; Daniel, Yiu; Michele, Colledan; Enrico, Regalia; Giorgio, Rossi; Marco, Angrisani; Dario, Consonni; Gianluca, Fornoni; Giuseppe, Piccolo; Maria, DeFeo T. title: The impact of the COVID‐19 outbreak on liver transplantation programs in Northern Italy date: 2020-05-22 journal: Am J Transplant DOI: 10.1111/ajt.15948 sha: 5276e926bceb4a0aa0fe1ad5acced88bef4a9213 doc_id: 703187 cord_uid: azq82peq In January 2020, Novel Coronavirus Disease 2019 (COVID‐19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID‐19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18‐74) whereas mean recipient age was 55 (13‐69); mean MELD score was 12 (6‐24). All donors underwent screening for SARS‐CoV‐2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post‐LT (range 3‐46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement. In December 2019, the world saw the initial reports of a new respiratory illness in patients from Wuhan, China. The disease rapidly spread There is currently a large degree of uncertainty toward the management of LT programs during the coronavirus outbreak. Our aim is therefore to share our observations on the coronavirus outbreak in order to demonstrate the impact that such a disease may have on liver transplant programs. Specifically, we aim to identify: 1. If the outbreak of coronavirus has led to a decrease in the number of LTs, and the reasons for this. Regional (Lombardy) data on patients with confirmed COVID-19 were gathered prospectively from January 30, 2020 onward. We compared data regarding liver donations in NITp area We analyzed the number of liver donations performed in Lombardy from January to March 2020. We calculated percent reduction and 95% confidence intervals (95% CI) of mean weekly counts of donors (referred and recovered) in the 4 weeks period from February 23 (period 1) with those in the previous 8 weeks (period 0), using univariate Poisson regression. Statistical analysis was performed with Stata 16 (StataCorp. 2019). We prospectively collected data on LTs performed in Lombardy before and after the onset of the outbreak. Data regarding donors (age, laboratory data, ICU days, BMI, city of residence, graft), recipients (age, gender, basic laboratory data, MELD score, BMI, disease, city of residence, immunosuppression, hospitalization days, outcome, surgical and medical complications, tests for coronavirus), LT (date, ischemia time), and retransplantation procedures performed in the Lombardy Region were collected prospectively from February 23, 2020 onward. The survival of liver-transplanted patients from February 23, 2020 to April 10, 2020 was documented. The study was approved by the Ethical Committee of the promoting center. Lombardy rose sharply (see Figure 1 ). The Councils of Ministers enacted new 9 decree-law 3 (from February 23 to March 22) in order to contain the outbreak. It was initially decided that more than 50 000 people from 11 different municipalities in Northern Italy were to be quarantined; however, shortly afterward, this was expanded, leading to the cessation of all commercial activity across Italy (March 21), with the exception of supermarkets and pharmacies. Data regarding donors, recipients, and transplantation procedures are reported in Figure 6 . F I G U R E 2 Donors referred and recovered in Lombardy before and after the onset of outbreak (the arrow shows the beginning of the outbreak) The first LT in Italy dates back to 1983, and to date (December 2019) 24 518 LT have been performed. 1 F I G U R E 3 Liver transplantations in Lombardy before and after the onset of outbreak (the arrow shows the beginning of the outbreak) There are currently 21 active liver transplant units, and according to European Liver Transplant Registry 9 these units are operating at the rate of more than 1000 liver transplants per year. In 2019, 1302 liver transplants were performed, including 1278 liver transplants from brain-dead donors. 10 As the impact of COVID-19 during the start of the outbreak was not well established, the National Department of Transplantation In However, caution is still required as we do not yet know the full impact of the infection as it spreads to more diverse populations. Although authorities in Italy have not formally halted the transplant programs across Lombardy, several factors have contributed to a temporary decrease in LTs: 1. There has been an overwhelming influx of COVID-19 patients to ICU beds. This has affected both the identification process for potential donors, as well as the availability of beds for recipients. 5. As already reported by others there are concerns regarding the safety of the procurement teams, 13 who may be exposed to potentially infected patients during the procurement process. Ideally the procurement team should not be sent to the donor hospital advising the local team at the donor hospital for organ retrieval and sending to the recipient hospital. If organization and the situation at a local level permits, there must be a careful risk/benefit analysis for performing transplantation, taking into consideration the recipient's risk of dying of endstage liver disease or cancer vs the risk of COVID-19. Therefore, during an outbreak, we advise the avoidance of performing LTs in nonurgent cases, with LT reserved to those patients with true endstage liver disease and extremely poor prognosis. A table summarizing key lessons that we learnt from our experience is reported in Figure 7 . We suggest the addition of Basiliximab to the immunosuppressive protocol. No serial test for Sars-CoV-2 should be performed in the post-op time in asymptomatic recipients; a swabbing test should be performed in case of fever or elevated CRP of unknown origin. If persisting doubts perform a chest CT scan. After discharge, minimize patients coming to hospitals for outpatient follow up, unless strictly necessary. 14 Evaluate and reserve LT to only recipients with incredibly poor prognosis and those with advanced HCC. The primary limit of our study is the short follow-up time for our patients. If serious complications are reported in the future, though the adoption of all measures to obviate them, then the evidence surrounding the management of liver transplant programs during outbreaks should be reconsidered. Furthermore, it should be noted that data concerning the number of infected patients in Italy from March 1 onward is not likely to be representative of the true number of cases, as testing was limited to only patients who were exhibiting symptoms. During the current ongoing outbreak of SARS-CoV-2 in Lombardy, Italy, there is a drastic decrease in the number of LTs performed. The main reasons behind this are the lack of ICU beds, organizational difficulties for ICU workers and concerns for infection in both patients and staff. On the basis of our results, this study has found no specific reason concerning the safety of liver recipients to stop LT programs. However, due to the complex circumstances which surround the viral outbreak, a rapid cessation or limitation of activity is often required pragmatically. Over the short follow-up period, the current survival of liver-transplanted patients during the coronavirus outbreak is quite good. However, the positivity of two patients after LT and the death of one of them, raises important questions regarding the facilitation of liver transplants during an outbreak. We suggest that only patients with true end-stage liver disease and extremely poor prognosis should undergo LT. We believe that COVID-19 protocols should include screening for both donors and recipients prior to LT. Testing both patient populations advocates not only for the safety of the recipients but also of the health workers too. BAL is the preferred method for recipient screening, either performed prior or immediately after the transplant procedure as this allows for rapid availability of reliable results. Different measures and precautions are to be taken in order to promote the safety of LT during the coronavirus outbreak. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Data are available from the authors on request. Maggi Umberto https://orcid.org/0000-0002-5337-2866 De Carlis Luciano https://orcid.org/0000-0002-9133-8220 Consonni Dario Fornoni Gianluca The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Covid-19 Coronavirus outbreak COVID-19 and Italy: what next? 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