key: cord-0789717-2doluywg authors: Waisberg, Daniel Reis; Abdala, Edson; Nacif, Lucas Souto; Haddad, Luciana Bertocco; Ducatti, Liliana; Santos, Vinicius Rocha; Gouveia, Larissa Nunes; Lazari, Carolina Santos; Martino, Rodrigo Bronze; Pinheiro, Rafael Soares; Arantes, Rubens Macedo; Terrabuio, Debora Raquel; Malbouisson, Luiz Marcelo; Galvao, Flavio Henrique; Andraus, Wellington; Carneiro‐D'Albuquerque, Luiz Augusto title: Liver transplant recipients infected with SARS‐CoV‐2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic date: 2020-08-04 journal: Transpl Infect Dis DOI: 10.1111/tid.13418 sha: abdb37a72f601302bbb9d3c097eab6dc4241b779 doc_id: 789717 cord_uid: 2doluywg The impact of coronavirus disease‐19 (COVID‐19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single‐center case series of five consecutive patients in the early postoperative period of deceased‐donor liver transplantation who developed nosocomial COVID‐19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID‐19 diagnosis on 9th postoperative day. The other was 67 years old with non‐alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti‐thymocyte globulin for treating steroid‐resistant rejection. Our novel experience highlights that COVID‐19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID‐19 nosocomial spread in the early postoperative period. Brazil is currently one of the most affected countries in the world by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has become the epicenter of the coronavirus disease-19 (COVID-19) pandemic in Latin America. 1 The impact of COVID-19 in liver recipients remains largely unknown, as most data derive from case reports and small retrospective series. [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Moreover, most of them address patients who were transplanted years ago. [2] [3] [4] [5] [6] [8] [9] [10] 12 Information regarding patients in the early postoperative period is very scarce. Many authors recommend weaning of immunosuppression and some even advocate its complete withdrawn. 2, 4, 9, 12, 16 Nevertheless, these suggestions are mostly based on patients in During the first months of the city quarantine (March 24th to May 31st, 2020), we performed 19 DDLT in 18 patients and di- Pathologists accredited) comprising an E gene assay as the firstline screening tool, followed by confirmatory testing with a N gene assay, as previously described. 17 Endogenous gene RNAse P was used as internal control of extraction and amplification, as well as positive and negative external controls. Analytical sensitivity was 40 copies/mL, and specificity in samples containing other respiratory viruses RNA was 100%. Table 1 depicts a summary of all cases, and Table 2 shows laboratory assessment at time of COVID-19 diagnosis. A 69 years old male patient underwent DDLT due to alcoholic cirrhosis and HCC. Postoperative course was uneventful, and he was discharged home on 8th POD. He returned to the emergency department on 10th POD complaining of fever, watery diarrhea, dry cough, and mild exertional dyspnea. A thoracic CT scan showed bilateral multiple ground-glass pulmonary opacities ( Figure 1C ), affecting less than 50% of the lungs. He was started on oseltamivir for 5 days, piperacillin/ tazobactam for 7 days, and oral metronidazole for 10 days. An RT-PCR in NO swab was positive for SARS-CoV-2. Shortness of breath worsened on the 10th day of hospitalization. Another thoracic CT scan showed increase in number and dimensions of ground-glass opacities, now affecting more than 50% of the lungs ( Figure 1D ). He could nonetheless sustain adequate levels of O 2 saturation on Venture mask 50% and did not require further interventions, being discharged home on 17th hospitalization day. A 59 years old male patient with cryptogenic cirrhosis underwent an uneventful DDLT. The patient was extubated on 1st POD, but A 34 years old male patient with sclerosing primary cholangitis and cirrhosis underwent DDLT with biliodigestive anastomosis. TA B L E 2 Laboratory assessment on COVID-19 diagnosis lobes. Almost total atelectasis of the right lower lobe due to adjacent pleural effusion was also noted, which was eventually drained via needle thoracocentesis ( Figure 1E,F) . Despite the more aggressive immunosuppression, the patient remained well with adequate O 2 saturation on oxygen catheter and was discharged home on 41st POD. Regarding the specify treatment of COVID-19, we followed our institution's protocol, in which most novel drugs, such as umifenovir, , showing bilateral multiple ground-glass pulmonary opacities, sometimes associated with thickening of interlobular septa and fine reticulate, affecting less than 50% of the lungs. D, Thoracic CT scan of the same patient on 20th POD, performed due to shortness of breath worsening, revealing increase in number and dimensions of ground-glass pulmonary opacities, now affecting more than 50% of the lungs. E and F, Thoracic CT scan of patient 5, showing numerous bilateral peribronchovascular ground-glass opacities, mainly in the upper lobes, some with thickening of the inter and intralobular septa. There is also a large pleural effusion on the right side with restrictive atelectasis of the adjacent pulmonary parenchyma (E-axial view, F-coronal view) lopinavir/ritonavir, and tocilizumab, 2, 4, 9, 12, 16 Therefore, it is reasonably safe to assume that we experienced a nosocomial spread of the virus, probably carried out by asymptomatic patients, or even by patient's visitors and healthcare personnel. Due to these events, infection control protocols were tightened, including a temporary ban on family visits, strengthening of barriers precautions, and mass SARS-CoV-2 screening for healthcare professionals. We also included the RT-PCR for SARS-CoV-2 in NO swab in the recipients screening. Although those infection control protocols with strict barrier precautions may reduce SARS-CoV-2 nosocomial spread even in immunosuppressed patients, 22 the challenge of maintaining large liver transplant programs in areas with high community transmission of SARS-CoV-2 will remain until a vaccine is developed. In conclusion, we reported a case series of liver recipients who developed SARS-CoV-2 infection in the early postoperative period, probably related to a nosocomial outbreak. Our experience highlights that COVID-19 may impact negatively the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID-19 nosocomial spread. The authors declare that they have no conflict of interest with regards to the content of this manuscript. Lucas Souto Nacif https://orcid.org/0000-0002-7059-3978 COVID-19 in Brazil: historical cases, disease milestones, and estimated outbreak peak Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient COVID-19 in longterm liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy Fatal outcome in a liver transplant recipient with COVID-19 Determining risk factors for mortality in liver transplant patients with COVID-19 COVID-19 in solid organ transplant recipients: a single-center case series from Spain COVID-19 associated hepatitis complicating recent living donor liver transplantation Earliest cases of coronavirus disease 2019 (COVID-19) identified in solid organtransplant recipients in the United States COVID-19 in solid organ transplant recipients: initial report from the US epicenter The impact of the COVID-19 outbreak on liver transplantation programmes in Northern Italy How to guarantee liver transplantation in the north of Italy during the COVID-19 pandemic. A sound transplant protection strategy Clinical course of COVID-19 in liver transplant recipient on hemodialysis and response to tocilizumab therapy: a case report Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients Perioperative presentation of COVID-19 disease in a liver transplant recipient COVID-19 in liver transplant recipients: an initial experience from the U COVID-19 in solid organ transplantation patients: a systematic review Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR Changes in liver transplant center practice in response to COVID-19: unmasking dramatic center-level variability Early impact of COVID-19 on transplant center practices and policies in the United States How to guarantee liver transplantation in the north of Italy during the COVID-19 pandemic: a sound transplant protection strategy Lessons from SARS-CoV-2 screening in a Brazilian organ transplant unit. Transplant Infect Dis Specific organization for in-hospital belatacept infusion to avoid nosocomial transmission during the SARS-CoV-2 pandemic Liver transplant recipients infected with SARS-CoV-2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic