ABSTRACT
In patients with Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS), the dysregulated immune response together with the use of immunosuppressive drugs has raised some concerns about the increased susceptibility to SARS-CoV-2 infection and the efficacy of anti-SARS-CoV-2 vaccines. Moreover, COVID-19, SLE, and APS share pathogenic pathways that may be responsible of common clinical and laboratory features and may explain why some drugs approved for SLE treatment were considered as potential treatment for COVID-19 disease. Another concern relies on "post-COVID syndrome” (the persistence of debilitating symptoms such as fatigue, dyspnea, and cognitive dysfunction) that could be confused with signs of SLE or APS. This chapter describes the common pathogenic mechanisms and clinical manifestations of COVID-19, SLE, and APS. Management strategies and immunogenicity and safety of COVID-19 vaccines are addressed. A focus on pregnant patients is also provided. Finally, similarities and differences between post-COVID syndrome and SLE/APS manifestations are described. © 2023 Elsevier Inc. All rights reserved.
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
Background: Anti-SARS-CoV2 vaccines showed a good efficacy in prevention of severe COVID-191. Their potential in induction of autoantibodies (abs) has not been well established1. One recent study demonstrated an increase of abs' titre after anti-SARS-CoV2 vaccination only in patients with already pre-existing positivity2. Objectives: To evaluate the potential induction of abs after anti-SARS-CoV2 vaccination in a triple positive antiphospholipid antibodies (aPL) cohort. Methods: 18 subjects were enrolled [M/F= 17/1;median age=52 years;5 Primary Antiphospholipid Syndrome (PAPS), 5 Systemic Lupus Erythematosus (SLE) with associated APS and 8 aPL carriers (1 Behçet Disease, 1 SLE, 4 Undifferentiated Connective Tissue Disease, 2 with no diagnosis of systemic autoimmune disease)]. Serum samples were collected before the first (T0) and at least one month after the second administration (T1) of the anti-SARS-CoV2 vaccine (16 BNT162b2, 1 mRNA-1273, 1 Gam-COVID-Vac). A wide panel of abs were evaluated through routinely methods. Results: None developed any additional sign of autoimmune diseases upon vaccination. Patients majority did not display any new autoantibody posi-tivity (Table 1). Changes were observed in 3 patients: 1) one aPL carrier patient who was antinuclear antibodies (ANA) negative at T0 was found to be ANA positive at T1 [negative anti-double stranded DNA and anti-extractable nuclear antigen (ENA)];this patient was actually ANA positive in her clinical history;2) one aPL carrier patient affected by SLE, who was IgM and IgG aCL and IgG aB2GPI positive at T0, turned positive for IgM and IgA aB2GPI;3) one aPL carrier patient affected by Behçet Disease, who was positive for IgM aCL and for IgM aB2GPI at T0, turned positive for IgA aCL and IgA aB2GPI. All emerging aPL were low titre. None of the patients displayed raising aPL titres from low to medium-high. Conclusion: Anti-SARS-CoV2 vaccination did not induce any clinical signs of autoimmunity in a cohort of patients with triple aPL positivity. Serology for autoantibodies remained stable in the majority of patients. Few patients experienced the emergence of low titre aPL, possibly as an expected inter-assay variation rather than an evolving 'serological fare'.
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.