Study group

We collected data for 115 pARD and divided them into two groups. We included 92 pARD after SARS-CoV-2 infection (Group 1) and 47 pARD after vaccination with two doses of the BNT162b2 Comirnaty vaccine (Group 2). Of those, 24 patients were included in both groups as they were infected with SARS-CoV-2 before or after vaccination. Study group characteristics are summarised in Table 1. The mean age was 13.4 (S.D.=4.1) years in Group 1, and 15.9 (S.D.=2.4) years in Group 2; 73% of patients were female in Group 1, and 64% in Group 2. The most common diagnosis was JIA, with 81% in Group 1 and 86% in Group 2. Other diagnoses such as SLE, vasculitis, uveitis, jDM, CRMO, jLS, rheumatic fever, CAPS, and UCTD were less common (Table 1).

In 47 pARD, a total of 94 vaccinations were performed. On average, patients received the second dose of vaccine 3.7 (S.D.=1.4) weeks after the first dose.

Altogether, we registered 103 SARS-CoV-2 infections. In 94 (91%) cases, a nasal swab was collected and either a real time RT-PCR or rapid antigen test for SARS-CoV-2 was performed. The results were positive in 65 (69%) and negative in 29 (31%) cases. Of the patients with a negative SARS-CoV-2 direct test, 20 (69%) reported contact with a SARS-CoV-2 positive person (positive contact) and had typical clinical symptoms of COVID-19. The other 9 (31%) also reported positive contact but did not recall any symptoms of COVID-19. In these patients, SARS-CoV-2 infection was confirmed retrospectively with serology.

SARS-CoV-2 testing data were not available for 9 (9%) cases. Seven (78%) reported positive contact and typical clinical symptoms of COVID-19. The other two (22%) also reported positive contact but no clinical symptoms, thus SARS-CoV-2 infection was confirmed retrospectively by positive IgG anti-SARS-CoV-2 antibodies.

Table 1 Patients’ basic characteristics

In Group 1, 69 (75%) patients were receiving immunomodulatory medications (Table 2). Twenty-three (25%) were using conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), 30 (33%) were using biologic DMARDs (bDMARDs), and 16 (17%) were using a combination of csDMARDs and bDMARDs. Fifty-one (74%) were receiving one, 16 (24%) were receiving two, one (1%) was receiving three, and one (1%) was receiving four medications. Twenty-three (25%) patients were not taking any medications at the time of SARS-CoV-2 infection.

In Group 2, 32 (68%) patients were receiving immunomodulatory medications (Table 2). Ten (21%) were using csDMARDs, 10 (21%) were using bDMARDs, and 12 (26%) were using a combination of csDMARDs and bDMARDs. Seventeen (53%) were receiving one and 15 (47%) were receiving two medications. Fifteen (32%) patients were not taking any medications at the time of vaccination against COVID-19.

The mean JADAS10 score in patients with JIA before vaccination was 1.1 (S.D.=1.75). Three patients with JIA had a JADAS10 score ≥ 5, their scores were 5, 6, and 7, respectively. Before vaccination, patients with other diagnoses were mostly in remission. The exception was one patient with jLS who had active lesions, but she was vaccinated before her first visit to the clinic.

Table 2 Medications among patients Clinical presentation of COVID-19

Altogether we recorded 103 infections in 92 patients, of whom 11 (12%) got the infection twice. The mean time between the first and the second infection was 45.6 (S.D.=13.1) weeks. In 14 (14%) cases, the infection was asymptomatic, 69 (67%) had a mild and 19 (18%) a moderate clinical presentation. One (1%) patient required hospitalization.

The first pARD in Slovenia were vaccinated at the end of March 2021. A subgroup of patients who had COVID-19 between April 2021 and April 2022 consisted of 62 patients. Nineteen (31%) patients were fully vaccinated; 16 (84%) of them had a mild and 3 (16%) a moderate clinical presentation. On average, the vaccinated patients contracted SARS-CoV-2 21.3 (S.D.=9.2) weeks after receiving the second dose of the BNT162b2 Comirnaty vaccine. Three of these 19 patients contracted the infection twice, first before vaccination (before April 2021) and for the second time after receiving both doses of vaccine. None of the patients were infected between the first and the second vaccination.

The other 43 (69%) patients were infected between April 2021 and April 2022 and were not vaccinated; three (7%) were asymptomatic, 30 (70%) had a mild and nine (21%) had a moderate clinical presentation, one (2%) required hospitalization. It seems that pARD who were not vaccinated before COVID-19 had a more challenging clinical presentation of the infection than those who received two doses of the vaccine before they were infected. The difference in the severity of clinical presentation of COVID-19 between vaccinated and unvaccinated pARD was not statistically significant (p = 0.31). The one patient that required hospitalization due to SARS-CoV-2 infection was unvaccinated.

We also compared the severity of the clinical presentation of COVID-19 between pARD who were receiving medication and those who were not on any medication at the time of infection. The results were not statistically significant (p = 0.31). Furthermore, we compared the severity of the clinical presentation of COVID-19 between pARD without medication and pARD who were receiving bDMARDs at the time of infection. Again, the results were not statistically significant (p = 0.68).

Relapse rate of autoimmune rheumatic disease after COVID-19 and after vaccination against COVID-19

Of 103 infections with SARS-CoV-2, relapse of ARD was registered after 10 (10%) infections. The relapse was mild in four and moderate in five cases. One patient had a severe relapse of ARD and required hospitalization.

Among pARD who had a relapse after infection (Group 1), seven had JIA, one had systemic JIA (sJIA), and the other two had Sjögren’s syndrome and chronic idiopathic uveitis, respectively. One patient among the seven with JIA had a relapse of uveitis, so JADAS10 could not be evaluated. For the patients who had a relapse of ARD after COVID-19, the JADAS10 before and after the infection are represented in Table 3, where applicable.

Table 3 pARD with a relapse of ARD after infection and after vaccination with JADAS10 where applicable

On average the before JADAS10 in Group 1 was evaluated 10.1 (S.D.=7.5) weeks before the infection, and the after JADAS10 7.2 (S.D.=4.4) weeks after the infection.

Patients in Group 1 who had a relapse of ARD after infection seem to have had a more challenging clinical presentation of the infection than those who did not have a relapse (Table 4). However, the difference in relapse rate depending on clinical presentation of COVID-19 was not statistically significant (p = 0.25).

Table 4 Clinical presentation of COVID-19 and relapse of ARD after infection

In Group 2, three (6%) among 47 vaccinated pARD had a relapse of ARD after vaccination. The relapse was mild in two pARD and moderate in one pARD. The patient who had a moderate relapse of disease after vaccination had an active ARD before vaccination with a JADAS10 score of 6. Severe relapses of ARD within this group were not recorded.

All three patients who had a relapse of ARD after vaccination had JIA. JADAS10 before and after vaccination against COVID-19 are presented in Table 3. On average the before JADAS10 in Group 2 was evaluated 5.7 (S.D.=1.2) weeks before the first dose of vaccine, and the after JADAS10 6.3 (S.D.=5.2) weeks after patients received the dose of the vaccine that caused the relapse. Two pARD had a relapse after the second dose and one after the first dose, however, he was still able to get the second dose as planned (4 weeks after the first dose).

The difference between the relapse rate in Group 1 (after infection) and Group 2 (after vaccination) was not statistically significant (p = 0.76). Moderate relapse of ARD was more common after the infection compared to vaccination, but the difference was not statistically significant (p = 0.19).

We looked at the occurrence of a relapse of ARD within three groups of patients: without medication, on bDMARDs, and on other medication, at the time of infection or vaccination. The results are presented in Table 5. No statistically significant differences were noted (p = 0.09 after infection and p = 0.30 after vaccination).

Table 5 Relapse of ARD after infection and vaccination based on medication of ARD