Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

New onset and flare of rheumatic diseases following COVID-19 vaccination are mild and respond well to treatment: 9-month follow-up data from a single centre cohort.

OBJECTIVES: Anti-COVID-19 vaccines have proved to be effective and well tolerated. Great attention is now being paid to the characterisation of possible adverse events associated to their administration. We report a case series of suspected rheumatic diseases (RDs) following anti-COVID-19 vaccination. METHODS: We included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padova University Hospital between May and September 2021 presenting with a RD within 30 days after an anti-COVID-19 vaccine dose. Our selection was in accordance with the World Health Organisation guidelines for adverse event following immunisation (AEFI) surveillance. Patients were regularly re-evaluated by telemedicine or face-to-face visit. RESULTS: We identified 30 cases of RD following vaccination: 24 (80.0%) new onsets and 6 (20.0%) flares. Most of patients (76.6%) received the BNT162b2 vaccine. The mean time to RD onset/flare was 12±9 days. The most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (33.3%) and adult-onset Still's disease (13.3%). At the last FU visit (9.6±2.2 months), 83.3% of patients showed complete response to first- or second-line therapy, 13.3% a partial response and one patient (3.3%) was still experiencing an active disease. CONCLUSIONS: Considering the amount of vaccine doses administered during the evaluation period we overall detected a limited number of cases. We noted a clear prevalence of autoinflammatory conditions and seronegative manifestations. The great majority of patients had mild features and showed a good response to therapy.

Post-COVID-19 arthritis: a case report and literature review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the novel pathogen responsible for the coronavirus disease 19 (COVID-19) outbreak. Researchers and clinicians are exploring the pathogenetic mechanisms of the viral-induced damage and growing interest is focusing on the short-term and long-term immune-mediated consequences triggered by the infection. We will focus on post-SARS-CoV2 infection arthritis which may arise as a new pathological condition associated with COVID-19. In this article, we describe a case of acute oligoarthritis occurring 13 days after a SARS-CoV2 severe pneumonia in a middle-aged Caucasian man and we go over a brief review of the current available literature. We hypothesize that molecular mimicry might be the basic immunological mechanism responsible for the onset of COVID-19-related arthritis based on the current knowledge of SARS-CoV2 and on the known pathogenetic mechanism of viral-induced arthritis.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Frequency and clinical correlates of antiphospholipid antibodies arising in patients with SARS-CoV-2 infection: findings from a multicentre study on 122 cases

OBJECTIVES: COVID-19 features include disseminated intravascular coagulation and thrombotic microangiopathy indicating a hypercoagulable state. We aimed to investigate antiphospholipid antibodies (aPL) prevalence and clinical relationships in a large cohort of COVID-19 patients. METHODS: We analysed the prevalence and titres of serum aPL in 122 patients with COVID-19 and 157 with primary antiphospholipid syndrome (PAPS) and 91 with other autoimmune rheumatic diseases (oARD) for comparison. IgG/IgM anticardiolipin (aCL) and IgG/IgM anti-beta2glycoprotein I (β2GPI) were assayed using homemade ELISA, IgA aCL and anti-β2GPI by commercial ELISA kits and lupus anticoagulant (LAC) by multiple coagulation tests following updated international guidelines. RESULTS: Prevalence of IgG and IgM aCL and of IgG and IgM anti-β2GPI across COVID-19 patients were 13.4%, 2.7%, 6.3% and 7.1%, being significantly lower than in PAPS (p<0.0001 for all). Frequency of IgG aCL and IgM anti-β2GPI was comparable to oARD (13.4% vs. 13.2% and 7.1% vs. 11%, respectively), while IgG anti-β2GPI and IgM aCL were lower (p<0.01). IgA aCL and IgA anti-β2GPI were retrieved in 1.7% and 3.3% of COVID-19 patients, respectively. Positive LAC was observed in 22.2% COVID-19 vs. 54.1% of PAPS (p<0.0001) and 14.6% of oARD (p=0.21). Venous or arterial thromboses occurred in 18/46 (39.1%) COVID-19 patients and were not associated with positive aPL (p=0.09). CONCLUSIONS: Thrombosis is a frequent manifestation during COVID-19 infection. However, prevalence and titres of aPL antibodies or LAC were neither consistently increased nor associated with thrombosis when measured at a single timepoint, therefore not representing a suitable screening tool in the acute stage of disease.