This prospective single-centre study focused on the clinical presentation of COVID-19 in pARD and the relapse rate of ARD in patients after COVID-19 infection and vaccination. The research was done amongst children, adolescents, and young adults with ARD. Currently, there are only a few studies reporting on the relapse rate of ARD after COVID-19 and/or after vaccination against COVID-19 [
8,
11,
23]. Therefore, this study contributes to the enrichment of knowledge in this field.
Clinical presentation of COVID-19
In our study, most patients were asymptomatic (14%) or had a mild clinical presentation (67%). Together, they accounted for 81% of all infections. A moderate clinical presentation was present in 18% of patients, and one patient (1%) was hospitalized. No-one suffered respiratory distress, and no-one required oxygen. The one patient who required hospitalization was admitted for dehydration. He had not been vaccinated prior to infection. None of the patients presented with MIS-C symptoms. Both patients treated with rituximab did not require hospitalization; one presented with a mild and the other with a moderate clinical presentation of COVID-19. In case of infection with delta virus they were advised to receive Regeneron, however, one notified us about the disease only after three weeks, and the other one had the omicron virus, so none received the antibodies. They also did not experience a relapse of rheumatic disease after COVID-19.
These findings are comparable to the available research. In a Turkish study by Sozeri et al., 113 children and adolescents with ARD on bDMARDs who recovered from COVID-19 were enrolled; 42 (37%) were asymptomatic, and 71 (63%) had COVID-19 symptoms. Of these 113 patients, 24 (21%) required hospitalization, and two (2%) even required intensive care therapy [
24]. Another study done in the USA by Villacis-Nunez et al. included 55 children and adolescents with ARD after COVID-19 infection. Of the 55 patients, 10 (18%) were asymptomatic, 35 (64%) had a mild or moderate clinical presentation, and 10 (18%) were hospitalized [
5].
In our study, asymptomatic clinical presentation (14%) was less common than reported in previously published studies. This was directly reflected in a higher number of patients with mild and moderate clinical presentation (85%). However, it was interesting to note, that only one patient (1%) required hospitalization, compared with 24 (21%) in the Turkish study, and 10 (18%) in the American study.
Relapse rate of rheumatic disease
Regarding the main objective of this study, we recorded 10 (10%) relapses of ARD after infection (Group 1) and 3 (6%) relapses of ARD after vaccination (Group 2). We observed a more challenging clinical presentation of COVID-19 in patients from Group 1 who later had a relapse of ARD, however, the connection between the severity of clinical presentation of COVID-19 and the relapse rate of ARD was not statistically significant (p = 0.25).
It is important to note, that in Group 1, four (40%) relapses were mild, five (50%) were moderate, and one (10%) was severe, and the patient required hospitalization to stabilize her ARD. In Group 2, two (66%) relapses were mild, one (33%) was moderate, and no one had a severe relapse of ARD after vaccination. Furthermore, the patient who had a moderate relapse of ARD after vaccination had an active disease with a JADAS10 score of 6 before vaccination. Usually, we aim to vaccinate pARD when the disease is in remission [
25]. However, because of the uncertainty surrounding COVID-19, there was a higher risk of infection, so pARD got vaccinated regardless of their current disease status.
We also observed that of the ten pARD who had a relapse after infection (Group 1), two patients received both doses of the vaccine before contracting COVID-19, and the other eight received none. It is important to note, that the two vaccinated patients had a relapse of the ARD twice. First, after they received the second dose of the BNT162b2 Comirnaty vaccine, and for the second time after COVID-19. Therefore, these two patients also represent two thirds of pARD who had a relapse after vaccination (Group 2). They had COVID-19 24.1 and 15.4 weeks, respectively, after second vaccination with BNT162b2 Comirnaty vaccine.
There was no statistically significant difference between relapse rates after infection and after vaccination (p = 0.75). However, there was a trend towards higher and more challenging relapse after the infection compared to vaccination.
Only a few studies have been published, reporting relapse rates of ARD in children and adolescents after COVID-19 or vaccination against COVID-19. A German study included 988 children with JIA and serology for COVID-19 was determined in 178 of them. Of these, 13 samples were positive. A relapse of ARD was observed in 7 out of the 13 children (54%). Two children had signs of arthritis flare after discontinuation of medication, and the remaining five had a relapse of ARD after COVID-19 even though the medications for their ARD remained unchanged [
8]. We can conclude that the relapse rate of ARD after COVID-19 in our study (10%) is much lower compared to the German study (54%). In our study, one patient had a relapse after stopping the bDMARDs and the second one had a relapse of ARD after lowering the dose of steroids, both changing their medications during the infection. This is comparable to the available data because we know that discontinuation of medication for ARD during COVID-19 can often lead to the exacerbation of ARD [
26].
A Turkish study by Haslak et al. enrolled 246 vaccinated adolescents with autoinflammatory and rheumatic diseases. They recorded a relapse in 27 (12%) patients [
25]. An Israeli study by Henshin-Bekenstein included 91 adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases. They reported changes in immunomodulatory drugs for eight (9%) patients after the first dose and for an additional four patients (5%) after the second dose of the BNT162b2 Comirnaty vaccine. Worsening of ARD symptoms was noted in five (6%) patients after the first dose and in one (1%) after the second dose, possibly demonstrating that not every medication change was a result of a disease relapse [
11]. These results are mostly comparable with the relapse rate of ARD in our study (6%). It is important to note, that one of our patients with a relapse of ARD after vaccination was not in remission at the time of receiving the vaccine (JADAS10 score of 6), and the second one discontinued part of her ARD medications on her own. Therefore, we cannot say with certainty that the relapse occurred because of vaccination.
The strength of this study is a relatively large study sample compared to the other published studies. Additionally, to our knowledge, this is the first study comparing relapse rates of ARD in paediatric patients after COVID-19 and after vaccination against COVID-19. Furthermore, it is important to note, that pARD, who were vaccinated, received two doses of the vaccine, respectively, but we counted both events as one, because the time span between the two doses was too short for the evaluation of the disease relapse after every dose.
This study also has some limitations. First and foremost, we must acknowledge the age difference in the patients enrolled in the study. Patients in Group 1 (after infection) ranged from 2 to 23 years, and patients in Group 2 (after vaccination) ranged from 10 to 21 years, since most vaccinated patients were 12 years old or older. The study only included patients from University Children’s Hospital Ljubljana, meaning it is a single-centre experience.