key: cord-0852566-tmykgbyo
authors: Patrono, Damiano; Lupo, Francesco; Canta, Francesca; Mazza, Elena; Mirabella, Stefano; Corcione, Silvia; Tandoi, Francesco; De Rosa, Francesco Giuseppe; Romagnoli, Renato
title: Outcome of COVID‐19 in liver transplant recipients: A preliminary report from Northwestern Italy
date: 2020-06-16
journal: Transpl Infect Dis
DOI: 10.1111/tid.13353
sha: 20d2e6c25fb24c2785367af63feb7c6ce7d75b2c
doc_id: 852566
cord_uid: tmykgbyo

Covid‐19 pandemic is deeply affecting transplant activity worldwide. It is unclear whether solid organ transplant recipients are at increased risk of developing severe complications and how they should be managed, also concerning immunosuppression. This is a report about the course and management of SARS‐CoV‐2 infection in liver transplant recipients from a single center in Northwestern Italy in the period March‐April 2020. Three patients who were treated at our institution are reported in detail, whereas summary data are provided for those managed at peripheral Hospitals. Presentation varied from asymptomatic to rapidly progressive respiratory failure due to bilateral interstitial pneumonia. Accordingly, treatment and changes to immunosuppression were adapted to the severity of the disease. Overall mortality was 20%, whereas Covid‐related mortality was 10%. Two cases of prolonged (>2 months) viral carriage were observed in two asymptomatic patients who contracted the infection in the early course after transplant. Besides depicting Covid‐19 course and possible treatment scenarios in liver transplant patients, these cases are discussed in relation to the changes in our practice prompted by Covid‐19 epidemic, with potential implications for other transplant programs.

Patient 1 was a 69-year-old gentleman with no major comorbidities, who received LT for hepatocellular carcinoma (HCC) arising on HBV and alcohol-related cirrhosis with model for end-stage liver disease score of 18 on March 5th, 2020. After an initially regular post-LT course, he was incidentally diagnosed as SARS-CoV-2-positive with a nasopharyngeal swab (NPS) on his 5th post-LT day (POD) after his bed neighbor, who was recovering from a liver resection for HCC, had tested positive the previous day. This last patient, who was the first patient being diagnosed COVID-19 in our unit and died of the disease 13 days later, also infected 8 staff members before being isolated, prompting a steep change in our practice (see Discussion).

Negative SARS-CoV-2 RNA test in the donor ruled out donor-recipient transmission. At the moment of diagnosis, patient 1 presented mild symptoms (rare coughs, temperature 37.5°C, no oxygen requirement). A computed tomography (CT) obtained on POD 6 did not show evidence of pneumonia ( Figure 1 ). He was transferred to a COVID unit on POD 9 where he was administered hydroxychloroquine (HCQ) 200 mg bid for 16 days (Figure 2 ). Mycophenolate mofetil (MMF) dosing was reduced from 750 mg td to 500 mg td, and target tacrolimus (Tac) trough level was set at 5-7 ng/mL. Blood tests ( Figure 3 ) were significant for mild lymphopenia, with levels comparable with those pre-LT. He had an otherwise asymptomatic and uneventful course and was discharged home in quarantine on POD 27. More than two months after infection, he is alive and symptomfree, but still waiting for confirmation of viral clearance, as he tested positive on the last NPS performed on day 42 after the first proof of infection.

Patient 2 was a 59-year-old gentleman who was admitted for Covid-19-related bilateral interstitial pneumonia (Figure 1) F I G U R E 1 Radiology findings. Only minimal alterations, not typical for COVID-19, were observed in patient 1, whereas patients 2 and 3 had findings compatible with bilateral interstitial pneumonia. Patient 3, left panel: initial X-ray showing no sign of pneumonia; right panel: X-ray upon re-admission, compatible with bilateral interstitial pneumonia March 8th, 2020, due to a weeklong history of fever, sore throat, dry cough, and odynophagia. Before admission, his liver function tests were normal and IS consisted in prolonged-release Tac 1 mg od and Eve 1.5 mg td. Vital signs on admission were T 38.2°C, BP 120/80 mm Hg, HR 60 bpm, RR 12, and SpO 2 99% in room air.

Although his chest X-ray was normal ( Figure 1 Figure 3 . He recovered well and tested negative for SARS-Cov-2 RT-PCR on three consecutive days (April 6th, 7th, and 8th) and was discharged home on April 9th.

Summary data for the whole series are provided in Table 1 , but some details are worth mentioning. First, all patients had good liver function at the moment of diagnosis.

Patient 4 was also a bed neighbor of our index patient, and he had been discharged from hospital before COVID-19 was made in this last. He tested positive for SARS-CoV-2 RNA on a NPS performed 2 months after his LT, without having been in contact with other known COVID-19 patients. Thus, it is likely that he contracted the infection in the early post-LT course, similarly to patient 1. As he was presenting no symptoms, no specific treatment has been administered and no changes have been made to his immunosuppression. antivirals (lopinavir/ritonavir and darunavir/ritonavir). Overall, mortality was 20% and COVID-related mortality was 10%. cases. In our opinion, notwithstanding that all efforts are mandatory to avoid infection of transplant patients, 11 risks associated with the current pandemic should be weighed against that of candidate death or drop-out from the list. Obviously, any reasoning has to be contextualized to local logistics and resources. 12, 13 In conclusion, age-matched mortality seems higher in LT recipients affected by COVID-19 as compared to the general population.

Future studies are necessary to determine the role of organ function, associated comorbidities, and IS. Finally, our experience suggests that maintenance of transplant activity in the midst of COVID-19 pandemic is possible, provided protected pathways are ensured.

DP involved in study design, data collection and analysis, and man- 

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