The survey received 167 responses. Seventeen responses were excluded from the analysis; 2 respondents were younger than 18 years old and 14 failed to answer the question about immunization status. One respondent had attested that they were older than 18 years old, but later marked that they were the patient, and selected a patient’s age younger than 18 years old. It was unclear which response was marked incorrectly, so we decided to exclude the patient from further analysis. Of the included patients, 131 had sJIA and 19 had AOSD. Among the 150 analyzed responses, 19 were from the affected subjects and 131 were from legal guardians responding on behalf of the patient.

Patient characteristics

Patient demographics are displayed in Table 1, stratified by immunization status and by diagnosis. While the is a growing understanding that sJIA and AOSD are a part of the same disease continuum, the median age of the AOSD population was 40 years old (IQR 34,60), which was markedly different than the median age of the sJIA patients (9 years old, IQR 6,13). Therefore, to be able to differentiate particularities about the immunization for the sJIA patients, they were reported separately from the full cohort. There was only 19 AOSD patients, of whom only one was not immunized, which limited the ability to perform separate analysis to this group, so they were reported together with the full cohort.

Non-immunized sJIA participants were younger than the fully immunized (median age 7.5 vs. 11, p < 0.001) and had a younger age of onset of disease (median age of onset 2 vs. 5, p < 0.001). There was a higher proportion of female participants in the immunized sJIA group compared to the unimmunized (78% vs. 56%, p = 0.011). About 3/4 of the respondents were from the United States, and most others were from English-speaking countries. The rate of immunization among AOSD was 95% vs. 62% in sJIA. Patients in both unimmunized and immunized sJIA groups had a similar history of disease complications such as macrophage activation syndrome (50% vs. 56%), arthritis (52% vs. 53%), and pericarditis/myocarditis (8% vs. 10%). The incidence of lung disease trended higher in the unimmunized group, although it was not statistically significant (30% vs. 20%, p = 0.207). The unimmunized group reported more disease flares and severe side effects from other immunizations compared with the immunized group (24% vs. 1%, p < 0.001). Table 2 lists medications ever used to treat sJIA/AOSD. The most used medications to treat sJIA/AOSD reported by respondents were glucocorticoids and inhibitors of IL-1 or IL-6 (Table 2). Other less frequent medications reported by the patients, which are not listed in the chart, were IVIG (1 patient), colchicine (1 patient), sulfasalazine (2 patients), certolizumab (1 patient), ruxolitinib (1 patient), mycophenolate mofetil (1 patient), joint injections (2 patients).

On average, unimmunized sJIA subjects had treatment histories that included a higher number of different medications, excluding non-steroidal anti-inflammatory medications, than immunized patients (median 7 vs. 5, p = 0.049).

Table 2 Medications ever used to treat sJIA/AOSDCharacteristics of immunized patients at the time of immunization

Table 3 lists the characteristics of immunized patients at the time of immunization. The majority of patients received the Pfizer/Biontech mRNA immunization (BNT162b2) (88% of sJIA and 78% of AOSD), followed by Moderna mRNA (12% of sJIA, 44% of AOSD), Oxford/Astra Zeneca (ChAdOx1) (1% of sJIA, 28% of AOSD%) immunizations, and Janssen (Johnson & Johnson, 2% of sJIA, 6% of AOSD). Approximately half of the patients reported inactive disease at the time of vaccination, while about a third had active disease when they were immunized. The most commonly used medications at the time of the immunization were oral steroids, IL-1, and IL-6 inhibitors. A complete list of medications used at the time of immunization is listed in Supplementary Table 1 in Additional File 1.

Table 3 Characteristics of immunized patientsPausing medications for the immunization

The full list of medications paused for the immunization is listed in Supplementary Table 1 in Additional File 1. Twelve patients out of 99 who were immunized paused medication before immunization, including 6 who withheld methotrexate (60% of sJIA patients on methotrexate at the time of immunization), and one patient each who withheld oral glucocorticoids (6%), anakinra (20%), tofacitinib (11%), tacrolimus (20%), adalimumab (100%), and other JAK inhibitors (25%). One patient paused both leflunomide and tacrolimus for the immunization. Among the subjects who were on multiple treatments and who held some medications, several chose not to interrupt treatment with other medications before immunization, including tocilizumab (3 patients), NSAIDs (5 patients), hydroxychloroquine (2 patients), infliximab (1 patient), canakinumab (1 patient), and cyclosporine (1 patient).

Side effects from immunization

Thirty-nine patients (39%) reported immunization side effects, which are listed in detail in Table 4. The most commonly reported side effects were local symptoms at the injection site, fever, chills, fatigue, myalgias, headache, nausea, lymphadenopathy, and rashes. Most side effects (79%) lasted 7 days or less, with the greater part lasting less than 2 days (41%). No medical care was required for the majority of patients. Thirteen patients reported severe and/or prolonged side effects, and they are described in detail in Supplementary Tables 2 and Supplementary Table 3 inside Additional File 1.

Table 4 Characteristics of immunization side effectsPericarditis

One 12-year-old male patient required an emergency department visit without the need for hospital admission following Pfizer immunization. He reported having had pericarditis as a side effect of the immunization. He did not specify the timing of this complication relative to the immunization. This patient had a prior history of pericarditis/myocarditis as a complication of his disease. His disease had been inactive at the time of the immunization, and he was only being treated with NSAIDs at the time.

Disease flares

A total of 6 patients (4 JIA and 2 AOSD) reported disease flares associated with the COVID-19 immunization. They are all listed in detail in Supplementary Table 2 on Additional File 1. Three patients marked “disease flare” as a side effect of the immunization. Three other patients reported disease flares as part of other comments of the survey. One patient (Patient 3), who did not report any side effects of the immunization, wrote in the comments that their child came out of remission 5 days after receiving the second dose of the COVID-19 immunization. The child is still having disease activity 7 months after the immunization. One patient reported a large flare 2 weeks after the second dose of the immunization. One patient reported a flare of Crohn`s disease after the immunization. Five out of the 6 patients who reported some type of flare with the immunization were on inactive disease at the time of immunization, and the majority of them did not hold medications for the immunization. Only the patient who had a flare of Crohn`s disease held methotrexate for the immunization but continued on infliximab. All the other 5 patients who flared did not hold their medications. Four of the 6 patients who flared with the immunization (patients 1, 2, 3, and 5) had a COVID-19 infection (3 after the second dose of the immunization, 1 after the third dose). All 4 of them also had a disease flare following the infection.

New onset of AOSD following COVID-19 immunization

Three patients reported to have had COVID-19 immunization as the trigger for their disease onset, and two of them required hospitalization. These were the only hospitalizations for immunization side effects. They are described in more detail in Supplementary Table 3 in the Additional File 1. One 63-year-old male patient reported having developed a multisystem inflammatory disorder akin to AOSD following the administration of the Oxford/ Astra Zeneca immunization. He required an ICU admission and he also reported to have developed atrial fibrillation and multisystem inflammatory syndrome in adults (MIS-A). It is unclear if the diagnosis was MIS-A or the new onset of AOSD. This patient did not specify which dose of the immunization triggered the reaction. However, he did receive a total of 4 doses of the immunization, including Pfizer/ BioNTech, and he reported having used anakinra at the time of the boosters, and he reported that he did not have the disease before the first dose. He did not specify if subsequent doses of the immunization triggered flares. One 35-year-old female patient developed symptoms of AOSD a few days after her immunization with Oxford/ Astra Zeneca immunization. She required hospitalization for her symptoms. One 60-year-old female patient developed symptoms of AOSD 10 days after receiving a booster with Moderna immunization. The patients did not specify if they had flares or side effects with subsequent doses of the immunization.

Reasons not to receive the COVID-19 immunization

Reasons cited by participants who decided not to receive a COVID-19 immunization are listed in Table 5. There was only one non-immunized AOSD patient, so all responses are reported together. The most common reasons were concerns about side effects from the immunization, both related to the diagnosis of sJIA/AOSD (29 patients, 58%), and unrelated to the diagnosis (23 patients, 46%). Sixteen (55%) participants who had concerns about immunization side effects related to sJIA/AOSD also had concerns about side effects not related to the patient`s condition. Fifteen out of 29 patients who had concerns specific to the underlying disease had a history of MAS, 9 had a history of sJIA-LD, and 3 had a history of pericarditis/myocarditis. Eleven patients reported concerns about the interaction of the immunization with their medications, including loss of effectiveness.

Six patients were told not to get the immunization by a medical provider. Four of these patients had a history of flares or severe side effects with other immunizations. Five of these 6 patients had a history of MAS, and 3 of the 5 also had a history of sJIA-LD. All of these 5 patients reported a history of multiple different immunomodulators, including IL-1 inhibitors, IL-6 inhibitors, tacrolimus, cyclosporin, and JAK inhibitors. Three of those patients had used emapalumab, and one of them had received a stem cell transplant. The patient who had no history of MAS was advised not to get the immunization due to long COVID-19 following infection.

Thirteen patients reported that the immunization was not available to the age group, and 1 patient reported an allergy to an immunization component. Eight patients reported other reasons for not receiving the immunization, which included one patient who reported a history of many severe medication allergies. One patient reported that they were told that they would need to stop the JAK inhibitors for one week before and one week after the immunization, and they were concerned with disease flare, so opted not to get the immunization. One patient believed that the benefit of the immunization did not outweigh the risk, citing the low risk of severe COVID-19 infection in pediatric patients. Two patients reported that the immunization had just become available to the age group and had not had a chance to get it yet.

Table 5 Reasons for not immunizingPatients with a history of MAS or lung Disease

Of 75 patients who reported a history of MAS, 50 received at least one dose of the COVID-19 immunization. Sixteen patients had active disease at the time of the immunization, 29 patients had inactive disease, 4 patients were in medicated remission, and one patient had abnormal labs. The survey did not specify if the patient had MAS at the time of the immunization. Nineteen patients reported side effects from the immunization, which were mostly mild and lasted 7 days or less. Three patients reported some type of flare associated with the immunization, which are described in more detail in Supplementary Table 2 (patients 3, 4, and 5), and two patients had side effects lasting 8 days or more (patients 7 and 10). Of 33 patients with a history of sJIA-LD, 27 of them also had MAS. Characteristics of patients with a history of sJIA-LD are described in more detail in Supplementary Tables 4, stratified by immunization status. Of note, two children with sJIA- LD patients reported a history of a bone marrow transplant. There was only one AOSD patient who reported to have lung disease. This adult patient added as a free text that they had been diagnosed with a rare primary immune dysregulation disease, and also had immunologic changes as part of the presentation.

COVID-19 Infection

Amongst the patients who answered the question about a COVID-19 infection, more patients tested positive for COVID-19 or had a diagnosis made by a medical provider in the unimmunized group compared with the fully immunized group (33/50, 66% vs. 46/95. 48%; p = 0.032). Three patients only received one dose of the immunization, and none of them had a COVID-19 infection. Some immunized patients contracted COVID-19 before receiving the immunization. Therefore, characteristics of the COVID-19 infection are listed in Table 6 stratifying patients according to the timing of the infection relative to the immunization and by diagnosis. Most patients had asymptomatic or mild/moderate symptoms. There was one ICU admission, which later resulted in death in a non-immunized patient, and there was one hospitalization to the general ward of an immunized patient. Patients with severe outcomes of COVID-19 infections are described in more detail in Supplementary Table 5. In the free comments section, five patients (patients A, B, D, F, and I) reported prolonged symptoms after a COVID-19 infection or reported having been diagnosed with long COVID in the comments. This was not specifically asked in the survey, so it is possible that more patients had this complication. Four of these patients contracted COVID-19 after having received a full immunization course.

MIS-C/ MIS-A

Eight sJIA patients reported developing MIS-C/MIS-A following a COVID-19 infection (6 of them had contracted COVID-19 without any prior dose of the immunization, and 2 patients contracted the infection after immunization with the Pfizer/BioNTech immunization, 1 patient after the second dose and 1 after the third.) The survey did not specify the dates of the infection, so it is not possible to determine the strain that caused it. These patients had a median age of 7.5 yo (IQR 2.5yo). One outlier patient was a 22 yo male. Seven of these patients had a history of MAS, and 4 of them had a history of lung disease. Seven of these 8 patients also reported having flared of the disease with the COVID-19 infection. Two patients (a 6 and a 4-year-old patient) reported that COVID-19 triggered the development of sJIA. One of these patients specified that the disease was diagnosed 6 weeks after the COVID-19 infection.

Table 6 Outcomes of COVID-19 infection (N = 79)Trend towards increased flare with COVID-19 Infection in unimmunized patients

Of the 79 patients who reported a history of COVID-19, we noticed a trend toward a higher risk of flare with infection amongst the un/incompletely immunized patients (20/46 patients − 43%) versus patients who had COVID-19 after at least 2 doses of the immunization (8/33 − 24%). This difference was not statistically significant (p > 0.05). Further confirming this, in a logistic regression including age, sex, age of onset of disease, diagnosis (AOSD vs. sJIA), immunization status, and history of immunization flare or severe side effects with other immunizations, only a history of flare or severe side effects with prior immunization had a statistically significant (p = 0.019) association with the risk of flaring with a COVID-19 infection. Only one of the patients who flared had held their medication for the immunization.