key: cord-0993603-15vmnt63 authors: Fonseca, Eduardo A.; Feier, Flavia; Pugliese, Renata; Freitas, Aline F.; Porta, Gilda; Miura, Irene; Baggio, Vera; Kondo, Mario; Benavides, Marcel; Vincenzi, Rodrigo; Roda, Karina; Oliveira, Caio V.; Chapchap, Paulo; Seda‐Neto, João title: Pediatric liver transplantation activity in a high‐volume program during the COVID‐19 pandemic in Brazil date: 2021-08-16 journal: Pediatr Transplant DOI: 10.1111/petr.14112 sha: 0d496ff3c9018f9d68bef87600b63b226cf901b2 doc_id: 993603 cord_uid: 15vmnt63 BACKGROUND: The impact of the COVID pandemic on liver transplant (LT) programs varied among countries. Few data are available about that impact in pediatric liver transplant (PLT) programs. This study aimed at comparing the data of our program in Brazil (2019 vs. 2020). METHODS: Retrospective cohort study. RESULTS: One hundred and seventy‐four PLT were performed in the period (93% living donors). Patients were divided into two groups according to the LT date: pre‐COVID‐19 period (march/2019–February/2020) and COVID‐19 period (March/2020–February 2021). In the pre‐COVID‐19 period, 97 LTs were performed, and 77 LTs were performed in the COVID‐19 period. Patients in the COVID‐19 period were younger (10.9 months vs. 16 months, p 0.009), had higher PELD scores (15 vs. 14, p 0.04), more ascites (66.2 vs. 51.5%, p 0.03), and more frequently hospitalized before LT (27.3 vs. 17.5%). However, there was no difference in post‐LT complications, retransplantation nor survival rates. Six (6.2%) patients from pre‐COVID‐19 period were COVID positive at a median of 15.5 months (14–17.5), and 6 (7.8%) patients from COVID‐19 period were COVID positive at a median of 3 months (20 days–6 months) from LT. There was neither mortality nor complications in those patients. Four (33%) were hospitalized, and one had prolonged intubation. Four (33%) were asymptomatic, 4 (33%) had upper airways symptoms, and the remaining had gastrointestinal symptoms. CONCLUSION: Overall, PLT was not affected during COVID‐19 period. Even though patients from COVID‐19 period were sicker, there was no significant impact in LT outcomes. All the recipients who tested positive for COVID had a favorable outcome. One year after the global report of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a total of 114 653 749 confirmed cases and 22 550 500 deaths were registered (until March 3, 2021) . Of the global numbers, 10 646 926 confirmed cases and 257 361 deaths were registered in Brazil, the second country with the highest cumulative confirmed cases and deaths. 1 The global impact on liver transplantation (LT) programs was notorious due to several factors: the shortage of intensive care unit (ICU) beds, precluding the performance of high-risk procedures such as LT, and the fear of the medical team and the patients of contracting COVID-19 in the hospital environment. 2 Additionally, in Brazil, there was a decrease in the number of transplantations due to a drop in the deceased donation rate, as well as in the number of transplants from live donors. 3 Countries that rely mainly on living donor liver transplantation (LDLT) also reported a decrease in the number of procedures performed during the pandemic. This effect was predominant in the beginning of the pandemic, improving somewhat after the centers established segregated patient flows to avoid cross-contamination. [4] [5] [6] [7] The balance between the continuity of transplant activity, while mitigating pre-transplant mortality versus the risk of recipient infection, determines the incorporation of strategic guidelines for COVID-19 that increase patient safety in this pandemic scenario. Such protocols must be adapted according to local and global epidemiological markers for transmission. Published studies suggest that children (≤17 years) infected with COVID-19 are less likely to progress to the severe form of the disease when compared to adults. 8, 9 However, scarce data are available on morbidity and mortality in children with comorbidities-such as candidates on the waiting list for LT -and the evolution of COVID-19 in those patients is still unpredictable. The aim of this study was to evaluate the impact of the COVID-19 pandemic in the pediatric LT activity in a high-volume program in Brazil and to compare the outcomes for those patients transplanted during the COVID-19 pandemic with those transplanted in the preceding 12 months. During the pandemic period, indications for LT were restricted due to The risks of exposing immunosuppressed recipients to SARS-CoV-2 in a hospital environment-as well as healthy donors, in the case of LDLT. Data on the hospital environment ensuring a COVID-19-free pathway, 10 as well as the severity status of the children on the waiting list, were taken into consideration when deciding to move forward with the LT. Therefore, candidates on the waiting list with higher mortality risk, that is, with higher pediatric end-stage liver disease (PELD) scores and/or with a recent decompensation requiring hospitalization, or in cases of malignancy, were considered for LT. 6, 11 Other markers for waiting-list mortality, such as ascites and hyponatremia, were also considered a priority for LT in our program. 12 The informed consent form was signed by the parents or guardians of the pediatric candidates, informing them about the risks related to SARS-CoV-2 infection during their hospital stay, and the false-negative rates of the polymerase chain reaction real-time (PCR-RT) test. The same applied to donors, in the case of LDLT. Organs from deceased donors were accepted when epidemiological and clinical screening and PCR-RT test for COVID-19 were negative. The LT procedures for these organs were approved only after the candidate had negative epidemiological and clinical screening; however, it was not possible to obtain the result of the candidate's PCR-RT test prior to LT. These recipients with unknown COVID-19 status were kept in a holding isolation area and triaged into the COVID-free or COVID areas once the PCR-RT results for COVID-19 were ready. These results were available at least 12 h after hospitalization. As for LDLT, both donors and recipients underwent epidemiological and clinical screening and PCR-RT testing for COVID-19 (nasopharyngeal samples) within 48 h before the planned LT. 6, 11 Only the pair of patients-donor and candidate-who presented full negative screening (epidemiological, clinical, and testing) were considered for LT. When the candidate and/or donor had clinical suspicion or active SARS-CoV-2 infection, the procedure was postponed until 28 days after symptom resolution, in addition to presenting two negative tests taken at least 24 h apart. 6, 13 Patients and donors involved in had a negative PCR-RT test. Scientific and clinical round meetings were done remotely. Remote telemedicine follow-up of outpatients was prioritized, and face-to-face returns were selectively requested. Hospital staff was reduced to avoid the risk of cross-contamination. Personal protective equipment (PPE) was used by physicians and HCW. After the LT, patients were not routinely tested for COVID-19, unless they had a positive epidemiological screening, or developed symptoms suggestive of SARS-CoV-2 infection. Only cases with a positive PCR-RT test were considered positive for COVID-19. Living donors' characteristics and postoperative outcomes, grouped by the Clavien-Dindo classification, 14 were also evaluated in both periods. Means and medians were calculated to summarize continuous effects, and the results were compared using t-tests or appropriate non-parametric tests when distributional assumptions were in doubt. Categorical variables are expressed as numbers and percentages. Differences between groups were assessed using chisquare or Fisher's exact tests, when needed. Significant differences were considered at a p < .05. Patient and graft survival analysis was conducted according to the Kaplan-Meier product-limit estimates, and patient subgroups were compared using a two-sided log-rank test. The incidence of COVID-19 infection was evaluated in both groups. A detailed description of those cases that tested positive for COVID-19 was included, as well as their outcomes. All analyses were performed using the SPSS 21.0 statistical package (IBM, Inc.). -19) , showed that those from the COVID-19 period were younger at LT, with higher PELD/MELD scores and greater prevalence of ascites, and were more frequently hospitalized before the LT (Table 1) . Waiting-list mortality rates in pediatric candidates were 8.4% and 11.9% in the pre-COVID-19 period and COVID-19 period, respectively. The postoperative outcomes analysis shows no significant differences between the periods, either in the length of hospital stay, or in the development of post-LT complications ( Table 2) . Two patients were retransplanted during the follow-up, one in each group. The 1-year patient survival was similar in both groups (95.9%, p = .9). There was no donor mortality, and 2 donors developed pulmonary thromboembolism, equally distributed among the periods, which were properly managed and had a good outcome. None of the donors were COVID-19 positive after the donation. A total of 12 patients, 6 (6.2%) from the pre-COVID-19 period and 6 (7.8%) from the COVID-19 period were infected, in a median of 15.5 months (14 to 17.5 months) and 3 months (20 days-6 months) after the LT, respectively. The clinical characteristics and outcomes of recipients diagnosed with COVID-19 are detailed in Table 3 . Questions related to which patients to transplant and which to postpone are relevant in this scenario. Our patients were continuously evaluated considering aspects related to the severity of the liver disease. In this series, LT was considered for those patients who were at real risk of death before LT, while waiting on the list. This is what has been recommended by other authors, and there is a consensus among them that LT should be indicated according to liver disease severity. Therefore, for those at higher risk of mortality on the waiting list, the procedure should not be delayed. 18 Comparative analysis of the clinical characteristics of candidates in the two groups showed sicker candidates in the COVID-19 cohort, with higher PELD scores, greater incidence of ascites, and longer hospitalization before LT. The LT cannot be considered independently as a factor associated with the risk of death for COVID-19, unlike comorbidities such as increased age, for example. 19, 20 This topic deserves attention when we analyze the risk of SARS-CoV-2 evolving to the severe form per age group. Previous studies demonstrated that severe manifestation of SARS-CoV-2 in children is uncommon. 21, 22 An Italian study in Bergamo, a location with a high incidence of COVID-19 transmission, involving children monitored for LT or with some degree of liver disease, demonstrated no increase in hospitalization or pulmonary involvement in COVID-19-infected children. 22 Our results demonstrated an incidence of COVID-19 infection in 6.9% of recipients, distributed similarly among the groups. Most patients had a favorable recovery, as published by other authors. 23, 24 Only 1 patient required prolonged intubation and oxygen support but did not present severe pulmonary involvement in imaging. The epidemiological and clinical screening of this candidate for SARS-CoV-2 was negative; however, the PCR-RT test for COVID-19 was positive 12 h after LT with a deceased donor. Most likely, this patient had an asymptomatic disease, a frequent situation in pediatric patients. 21 According to the recently pub- showed good recovery. The overall clinical outcomes in this study were favorable. The comparative analysis between the groups related to recipient and graft survival, vascular complications, and COVID infection after LT, indeed the end-points of this study, showed no significant difference between the periods. Thus, there was no negative impact on the outcomes of pediatric LT recipients during the pandemic. Donors also presented favorable results in donation-related morbidity according to the Clavien-Dindo criteria, and there was no difference between the two periods. The preliminary publication of our experience in a high-volume program of pediatric LT, at the epicenter of the pandemic, allows us to conclude that an initial reduction in transplant activity is justified until new COVID-free pathways are established to ensure patient safety. The comparative analysis with the period before the pandemic showed no negative impact on the results, supporting the continuation of this activity. All the authors listed have contributed to this work and meet the authorship criteria. The data that support the findings of this study are available from the corresponding author upon reasonable request. Eduardo A. Fonseca World Health Organization. Coronavirus disease (COVID-19) outbreak. 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