key: cord-0915318-u0fcs3yg
authors: Doná, Daniele; Torres Canizales, Juan; Benetti, Elisa; Cananzi, Mara; De Corti, Federica; Calore, Elisabetta; Hierro, Loreto; Ramos Boluda, Esther; Melgosa Hijosa, Marta; Garcia Guereta, Luis; Pérez‐Martínez, Antonio; Barrios, Maribel; Costa Reis, Patricia; Teixeira, Ana; Lopes, Maria Francelina; Kaliciński, Piotr; Branchereau, Sophie; Boyer, Olivia; Debray, Dominque; Sciveres, Marco; Wennberg, Lars; Fischler, Björn; Barany, Peter; Baker, Alastair; Baumann, Ulrich; Schwerk, Nicolaus; Nicastro, Emanuele; Candusso, Manila; Toporski, Jacek; Sokal, Etienne; Stephenne, Xavier; Lindemans, Caroline; Miglinas, Marius; Rascon, Jelena; Jara, Paloma
title: Pediatric transplantation in Europe during the COVID‐19 pandemic: early impact on activity and healthcare
date: 2020-08-12
journal: Clin Transplant
DOI: 10.1111/ctr.14063
sha: c8474dbf9fe0d54fd47cf9382296536fb52f1efe
doc_id: 915318
cord_uid: u0fcs3yg

The current pandemic SARS‐CoV‐2 virus has required an unusual allocation of resources that can negatively impact of chronically ill patients and high‐complexity procedures. Across the European reference network on pediatric transplantation (ERN‐TransplantChild) we conducted a survey to investigate the impact of the COVID‐19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell (HSCT) transplantation. The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified, restricted to selected ones and to the use of telemedicine tools has increased. Additionally, a total of 14 COVID‐19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate‐severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID‐19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long‐term consequences for pediatric transplantation candidates, recipients and their families.

Although global data are not yet available, published studies suggest that children (0-17 years old) correspond to less of than 5% of the total number of patients affected by COVID-19 and that children seem to have a less severe disease in comparison to adults 4, 5 . Indeed, although severe outcomes (including deaths) have been reported in the pediatric population 6 , relatively fewer children with COVID-19 require hospitalization or admission to the intensive care unit (ICU) 7 .

Those children with multiple co-morbidities are distinctively at a higher risk for severe illness.

However, information on specific risk factors, forms of presentation and prognosis of in pediatric transplantation patients is scarce.

The emergence of COVID-19 has had a profound impact in transplantation worldwide, not only with respect to issues around donors or recipients, but also healthcare resources utilization as the magnitude of COVID-19 cases in certain regions exceeds the available capacity of the health system 8 . At this early stage in the pandemic very little information is available regarding the risk and burden of COVID-19 in pediatric transplant recipients as well as direction regarding protocols to be applied in this special population 9, 10 Dealing with this situation, several interventions aligned with international recommendations 11-13 have been implemented in pediatric transplant centers. These include the application of protocols made for adult transplant Accepted Article recipients 14, 15 and the local adaptations of international guidelines [16] [17] [18] [19] for the diagnosis, prevention and management of SARS-CoV-2 infection. Professionals from all transplant programs, both hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), including kidney, lung, heart, pancreas, intestine, multivisceral or multi-organic, of the all 18 centers members of ERN TransplantChild distributed in 11 EU countries were invited to participate. The survey included relevant questions to: i) assess pediatric transplantation activity, including living-donation issues; ii) identify the protocols adopted to prevent and manage SARS-CoV-2 infection at the hospital level; iii) evaluate the impact of these practices on the healthcare of transplanted children; and iv), describe the management of confirmed COVID-19 cases among the special population of pediatric transplant recipients and candidates. The complete questionnaire is available online (https://ec.europa.eu/eusurvey/runner/TransplantChild_COVID19).

The survey focused on information from the centers during the 30 days since case reporting (Day 1) began in the participating countries. Total case and cumulative incidence data were obtained from the COVID interactive dashboard from the European Centre for Disease Prevention and Control (available online: https://qap.ecdc.europa.eu/public/extensions/COVID-19/COVID-

A confirmed case was defined by laboratory testing of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Cases were grouped by the manifestations of the disease by

This article is protected by copyright. All rights reserved their severity: mild disease (from asymptomatic to mild symptoms: fever, dry cough, tiredness, muscle aches or headache, sore throat or runny nose), and moderate/severe disease (pneumonia with dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation (SpO2) ≤ 93%, respiratory failure, septic shock, and/or multiple organ dysfunction).

The survey, published on the EU official web site, was accessible from April 8, 2020 until April 14, 2020 when all ERN-TransplantChild members completed the questionnaire. The survey results were summarized by a descriptive analysis using R statistical software, version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). 

As concerns pediatric transplant activity, 10 out of 18 centers (55%) remained active during the month of March 2020, while seven limited their activity to urgent cases and one completely suspended pediatric transplant programs. Besides COVID-19 transmission issues, in 4/7 centers where only urgent transplants were performed, the limitation was also due to limited resources, especially to the lack of availability of ICU beds for transplant patients. Overall, 12 of 18 centers

This article is protected by copyright. All rights reserved (67%) experienced a reduction (from 25 to 75%) of their usual workload during the study period (Table 1) . Only 3 programs (2 kidney and 1 liver) were not available to perform living donor transplantation; however, in the rest of the centers, the living donor was reserved for urgent cases. Cadaveric donors were available with specific local adaptations of the protocols for COVID-19 screening, although their accessibility was considerably reduced. In HSCT programs the problem was reflected in the unrelated donors from other countries, being influenced by quarantine mobility restrictions, since the limitations of the donor's displacement to the donation centers, to decreased shipping capacity.

Outpatient visits of pediatric transplanted patients were also affected by the COVID-19 outbreak in 17 out of 18 centers (96%). One center entirely suspended outpatient activity (Table 1) , nine centers limited the visits to selected patients, and seven centers started or increased the use of telemedicine. In eight centers (44%) outpatient visits were performed only after a telephone pretriage excluding epidemiological (e.g., close contact with a known COVID-19 case) and clinical risk factors (e.g., ongoing fever or respiratory symptoms in the patient or in the caregiver) for SARS-CoV-2 infection. This telephone pre-triage was extended to hospital admissions in 15 centers (83%). A negative nasopharyngeal swab for SARS-CoV-2 was also required before planned hospitalizations or procedures in 10 centers (55%). 

This article is protected by copyright. All rights reserved home through telemedicine, and to hospitalize only suspected cases with moderate-severe symptoms; three centers admitted for observation suspected cases for COVID-19 confirmation to all pediatric patients, regardless of symptoms severity; the other three centers decided on a case-by-case basis, depending on the patient's symptoms and requirements, as well as the available hospital resources.

With respect to caregiver policy during hospital stays, 17/18 centers allowed only one caregiver per patient, equipped with protective personal equipment (i.e. surgical mask); Moreover, at least 4 centers considered nasopharyngeal swab testing for SARS-CoV-2 in the caregiver to support the decision of which caregiver will stay with the child during admission.

We ask about the material that professionals use during their daily activity in the hospital. 

To determine whether participating centers had attended patients with COIVD-19, we initially asked for the number of pediatric patients who have been reported to the hospital. More than half of the participant ERN-TransplantChild centers (10/18) reported less than 10 COVID-19 had treated pediatric patients at the hospital level, six centers reported less than 30 cases, and only two centers reported more than 40 total cases in the pediatric population during the study period. Among affected children, the rate of ICU admission was less than 5% and no deaths were reported.

From the cases followed up by the respondent centers, until April 14, 2020, a total of 14 COVID-19 confirmed cases were reported among pediatric transplant candidates (kidney=2, liver=2, HSCT=2) and recipients (kidney=2, liver=3, HSCT=3) by five ERN-TransplantChild centers ( Figure   2 ). All the six children on the transplant waiting list and six out of 8 transplanted children experienced a mild disease, while two out of 8 pediatric transplant recipients (both HSCT)

This article is protected by copyright. All rights reserved presented a moderate/severe disease (Figure 1 ). Although these are still preliminary data, the treatment strategy varied among centers. Children with mild COVID-19 received supportive therapy for pediatric patients with COVID-19, without any modification of previous immunosuppressive treatment. The HSCT patients with moderate/severe COVID-19 were not on immunosuppressive treatment and received standard support treatment without complications.

No patients required admission to the ICU and no deaths were reported. 

This article is protected by copyright. All rights reserved almost half of pediatric transplant centers, a negative SARS-CoV-2 swab was also required as an additional admission criterion. Caregiver testing before admission was considered in some centers to allow them to decide who parent stay with the child, but in most cases, the caregiver's lack of symptoms was considered sufficient to contain the possible SARS-CoV-2 in-hospital spread. Moreover, even though the protection of healthcare workers is considered a priority, the test for SARS-CoV-2 infection was periodically performed in only one center, while no active surveillance was reported by the remaining respondents. Although professional screening was not common at this early stage of the pandemic, it will be important to be considered later phases, especially for those professionals who may have contact with higher risk patients with COVID-19, such as immunocompromised patients, to ensure that both healthcare personnel and patients are not put at risk.

A telephone pre-triage to exclude COVID-19 epidemiologic and clinical risk factors, could be a cost-effective strategy and was widely implemented before outpatient visits and hospital admissions. It is also important to highlight how, to overcome the issues related to lockdown, telemedicine technologies have been rapidly introduced to support some activities such as remote patient monitoring and management. This technology was already reported as a potentially valuable tool for the follow up of transplant patients, but experience is limited only to the outpatients setting 24 . Therefore, pediatric transplant centers need to be prepared for difficult and extraordinary situations, such as deciding which patients should be transplanted when resources are limited and the best care for those patients after transplant 8 . Indeed, each donorrecipient scenario may have different considerations in terms of resource limitations, potential benefits and risks 9, 25, 26 . It is also important to define an appropriate pathway to avoid posttransplant infection 27 . In epidemic regions, transplant centers need to carefully balance the costs and benefits in performing a transplant during the COVID-19 pandemic.

We also reported the occurrence and the outcome of SARS-CoV-2 infection in six children awaiting transplantation and eight pediatric transplant recipients. None of the candidates in the SOT waiting list, nor any of the SOT recipients presented a severe COVID-19 syndrome. The moderate-severe cases described were HSCT patients who were not being treated with immunosuppressive drugs but with probable impairment of their immune system either due to the transplant procedure itself or by the underlying disease 28 . Therefore, even if it seems that the

This article is protected by copyright. All rights reserved 32 . The treatment of these cases included immunosuppressors reduction, in addition to supportive measures; none of these cases required ICU, and the outcome was favorable, with no reported mortality.

Some limitations of the study methodology should be considered, including those inherent in a survey-based study. This survey reflects the practices adopted by professionals in each center, and while these are major national centers it does not necessarily reflect the situation at a national level. The availability of resources at each center also limits the ability to make universal recommendations in the care of pediatric transplant patients. Due to lack of experience in treating affected pediatric transplant patients, hospital admission criteria for suspected and confirmed COVID-19 cases varied between ERN-TransplantChild centers.

While the majority of centers considered admission of only moderate/severe COVID-19 cases and dealing with the milder ones through telephone calls or telemedicine, other centers preferred to admit all pediatric transplant patients regardless of symptoms. In contrast to adults, almost all ERN-TransplantChild centers had the capacity to admit critically ill pediatric transplant patients with suspected/confirmed COVID-19 into pediatric ICUs 33 as a low rate of severe COVID- 

This article is protected by copyright. All rights reserved 

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