ABSTRACT
Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.
ABSTRACT
Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.
ABSTRACT
In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.
ABSTRACT
BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.