key: cord-0872134-8dxd3iaq authors: Calvo, C.; Remesal, A.; Murias, S.; Ara-Montojo, F.; Otheo, E.; Sanz-Santaeufemia, F. J.; Villaroya, A.; Moraleda, C.; Tagarro, A. title: COVID-19 IN CHILDREN WITH RHEUMATIC DISEASES (RD) IN THE SPANISH NATIONAL COHORT EPICO-AEP. date: 2020-10-20 journal: nan DOI: 10.1101/2020.10.17.20214296 sha: 9064ed569df0532bdadc693af0238b00c6421a47 doc_id: 872134 cord_uid: 8dxd3iaq Objectives: SARS-CoV-2 infection in adults with rheumatic diseases (RD) is a cause for concern. Data in the pediatric population are practically absent. We aimed to describe the prevalence of patients with RD and their complications among children admitted with COVID-19 in the Spanish national cohort EPICO-AEP; a multicenter prospective national study. Methods: Children <18 years old with RD and COVID-19 enrolled in EPICO-AEP were included in this study. Results: By June 30th 2020, 350 children were admitted in secondary and tertiary hospitals of Spain with SARS-CoV-2 infection. A total of 8 patients presented RD (2.2% of those hospitalized). All were female. The median age was 12.1 years (IQR 8.3-14.5). The diagnosis related with COVID-19 were febrile syndrome and/or upper respiratory infection (4 cases) and pneumonia (4 cases). One of the 8 (12.5%) patients with a severe juvenile dermatomyositis (JDM) with interstitial lung disease died. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis in 3/8 (37.5%) patients. In 5/8 (62.5%) cases, the RD was not fully controlled, and all patients except one received corticosteroid treatment. Conclusions: Children with RD have accounted for 2.2% of hospitalized patients with COVID-19 in our series. The evolution has been moderately favorable, with one deceased. In case of active disease and use of corticosteroids patients should be managed with caution. Key words: COVID-19, children, rheumatic diseases, corticosteroids. SARS-CoV-2 infection in children is relatively mild, although the pediatric population suffers at least 10% of identified cases [1] with a small proportion of them requiring hospitalization. From 25% to 60% of admitted children with COVID-19 have comorbidities, including rheumatic diseases (RD) [2, 3] . Pediatric patients with RD often receive immunosuppressive medication and in theory, they are a group of risk. Studies in adults with RD show that immune-mediated inflammatory disease and use of biologics are not associated with worse COVID-19 [4] [5] [6] [7] . However, if patients have poorly controlled active RD or receive some treatments such as corticosteroids, they may have an increased risk of infection and serious disease . Based on the results of the published series, some scientific associations have relased management recommendations for these patients [8] . The American College of Rheumatology (ACR) has made recommendations for SARS-CoV-2 infections in children with RD, but they acknowledge the lack of pediatric data [9] . We aimed to describe the prevalence of patients with rheumatic diseases and their complications among children admitted with COVID-19 in the Spanish national cohort EPICO-AEP. The Epidemiological Study of COVID-19 in Children of the Spanish Society of Pediatrics (EPICO-AEP) is a multicenter prospective national study aiming to describe the pediatric COVID-19 in Spain. Children younger than 18 years with infection due to SARS-CoV-2 and attended at 49 hospitals were included in this registry. Inclusion criteria included positivity in real-time polymerase chain reaction (RT-PCR) in nasopharyngeal sample, IgM or IgG in lateral-flow rapid test, ELISA or chemiluminescence serology, or severe disease suggestive of multi-Inflammatory syndrome related to SARS-CoV-2 (MIS-C) and recent household contact with a All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 20, 2020. . confirmed patient with COVID-19. From March 1st to June 30th, 2020, children with RD and COVID-19 enrolled in EPICO-AEP were included in this study. This study was approved by the ethics committee of Hospital 12 de Octubre (code 20/101). Informed consent was obtained by parents and mature minors. Data were analyzed using the Stata version 15, College Station, TX. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 20, 2020. . Special mention deserves the patient with JDM, that has been previously published [10] . Anti-melanoma differentiation-associated We report the prevalence of children with COVID-19 and RD in the Spanish national EPICO-AEP cohort of hospitalized children. As far as we know, it is the first national All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 20, 2020. . cohort that collects children with RD, representing 2.2% of admitted children with COVID-19 in Spain. Although the general outcome was favorable, 1 patient (12.5%) died and 2 had thrombotic complications. Most of the patients received prednisone, which has been considered a drug that confers an increased risk of severe COVID-19 in adults with RD [4, 5] . The series published in adults agree that patients with RD have a similar risk to the general population of contracting a SARS-CoV-2 infection and those having other comorbidities like hypertension, diabetes or cardiac diseases are at higher risk of developing a more severe course of COVID-19 [4] [5] [6] [7] . However, certain conditions such as the presence of active disease, and some immunosuppressants confer an increased risk of hospitalization. Thus, in the German National register in 104 adults with RD and COVID-19, hospitalized patients were more often treated with glucocorticoids while biological disease-modifying antirheumatic drugs (DMARDs) were used less often [4] . The Global Rheumatology Alliance physician-reported registry [5] , with a total of 600 cases of COVID-19 in adults with RD from 40 countries, found that nearly half of the cases were hospitalized (277, 46%) and 55 (9%) died. In a multivariable-adjusted model, prednisone dose Chronic steroids have a strong immunosuppressive effect, as long as hypothalamichypophysis axis suppression. Our results, along with literature in adults, suggest that steroids might have more risk for COVID-19 admission than biologics. Pediatricians should be cautious when evaluating children on chronic steroids and COVID-19. For children with RD and COVID-19, the ACR [8] recommends maintaining treatment with NSAID, conventional DMARDs and biological DMARDs. Regarding glucocorticoids, the task force recommended that glucocorticoids should be continued or initiated when clinically indicated, using the lowest effective dose to control underlying RD without defining a specific dose (e.g., less than or equal to 10mg prednisone used in adults) for the pediatric population. In our patients, the treatment was not modified, except for azathioprine withdrawal in one case. Most patients had active disease, and the risk of withdrawal was considered higher than the risk of maintaining the drugs. Although more data in children with RD are necessary to release strong recommendations, our series seems to support that corticosteroid treatment may be a risk factor for hospitalization in this group of children. Data in the pediatric population are practically absent. In 2 series from Italy and UK, COVID-19 in children with rheumatic diseases were not reported [3, 11] . In our series, it is worth mention that 100% were females and age was higher than the overall cohort, possibly reflecting the pediatric population of patients with RD. Virtually all patients were receiving treatment with prednisone or MTX that have been found to risk hospitalization or serious illness in adults [6] . Importantly a significant percentage was in the early stages of the disease, without good control of it. Two patients had COVID-19 at the time of onset of RD, which raises the hypothesis if COVID-19 may have a role triggering the disease. This hypothesis have also been formulated for other autoimmune disease, as diabetes [12] . Overall outcome was good, except in the case of JDM, and interstitial lung disease has been recognized as risk factor of severe COVID-19 in adults [13] . Thrombotic complications are common in adults with COVID-All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 20, 2020. . In summary, in the Spanish national EPICO-AEP cohort, children with RD have National Trends of Cases of COVID-19 in Children Based on US State Health Department Data COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry Clinical course, severity and mortality in a cohort of patients with COVID-19 with rheumatic diseases Covid-19 in Immune-Mediated Inflammatory Diseases -Case Series from New York American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID-19 Pandemic: Version 1. Arthritis Rheumatol Fatal outcome of anti-MDA5 juvenile dermatomyositis in a pediatric COVID-19 patient: a case report Dealing with COVID-19 in a Pediatric Rheumatology Unit in Italy New-Onset Type 1 Diabetes in Children During COVID-19: Multicenter Regional Findings in the U.K. Diabetes Care Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease: An International Multicenter Study No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted This study has been partially funded by a grant from the Spanish Association of Pediatrics (AEP)