Clinical course of COVID-19 in children with rheumatic disease under biologic therapy

Demir, F.; Ulu, K.; Çaǧlayan, Ş Coşkuner T.; Sözeri, B.; Demir, Ferhat; Ulu, Kadir; Çaglayan, Sengül; Coskuner, Taner; Sözeri, Betül

Background: Since the beginning of the COVID-19 pandemic in our country, Turkey, more than two million people have been infected and more than 20,000 people have died. Although children infected less frequently and generally have a milder findings of COVID-19, the number of patients with a more severe clinical course as multisystem inflammatory syndrome in children (MIS-C) is increasing significantly. However, it has not been shown exactly how biological disease-modifying antirheumatic drug (bDMARD)s, which we frequently use in our pediatric rheumatology practice, and/or the underlying rheumatological diseases affect the clinical course of COVID-19. Objectives: Here, we aimed to reveal the outcome of COVID-19 infection in our patients with pediatric rheumatic disease and treated with bDMARDs. Methods: During the period between April 1, 2020 and December 1, 2020, the patients who received bDMARDs were evaluated at the regular outpatient clinic follow-up or by telemedicine with a maximum of 3 months interval. Clinical and demographic characteristics, COVID-19 data and outcome of these patients were retrospectively collected. Results: Out of the 436 patients treated with bDMARDs, 39 children were infected with COVID-19. The diagnosis was confirmed in 37 patients by RT-PCR (nasalpharyngeal swab) and in two by antibody test. Twenty-two (56.4%) patients were female (17 male, %43.6) and the median age of patients were 12.3 years (min-max: 1.2-20.9). The primary diagnosis of patients were as follows;20 juvenile idiopathic arthritis (six were systemic subtype), 12 systemic autoinflammatory diseases, three vasculitis, three chronic recurrent multifocal osteomyelitis and one Sjögren's syndrome. Prior to COVID-19 infection, 13 patients (33.3%) were using canakinumab, seven were infliximab (18%), five were adalimumab (12.8%), four were etanercept 10.2%), four were tocilizumab (10.2%), three were anakinra (7.7%), two were rituximab (5.1%), and one was tofacitinib (2.6%). Of the 39 patients, 21 had at least one COVID-19-related symptom, while 18 patients were asymptomatic. No laboratory or imaging tests was performed for asymptomatic patients and they were followed up without treatment at home isolation. Laboratory tests revealed that fourteen patients had elevated acute phase reactants, six had elevated D-dimer levels, three had lymphopenia (<1000/mm3), and three had hyperferritinemia. Hospitalization was required in 20 patients (51.3%) at median of 7-days (minmax: 3-17) and pediatric intensive care unit admission in one. Five patients developed MIS-C and one of these patients was followed up in the pediatric intensive care unit. Myocardial dysfunction was developed in this patient and he was died. The other four patients fully recovered with no remain morbidity. Conclusion: Considering the literature data and the results of our study, it is not possible to say that currently used bDMARDs worse the course of COVID-19 infection. In patients with underlying risk factors for hyperinflammation, as in one of our patients, COVID-19 may cause mortality regardless of the use of bDMARDs. Whether bDMARDs does not affect the severity of the disease, but it is still not true to say that these drugs are protective. Since cessation of bDMARDs for COVID-risk may cause exacerbation of the primary rheumatic disease, continuing with current treatments seems an appropriate approach.