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.

Obstetric Outcomes in Women with Rheumatic Disease and COVID-19 in the Context of Vaccination Status.

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi -square or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2%(n = 2). CONCLUSION: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.

Detection of Autoantibodies in Saliva as New Avenue for the Diagnosis and Management of Autoimmune Patients.

(1) Background: Autoimmune diseases are characterized by autoantibodies directed to a large number of antigenic targets and are measured using serum as sample matrix. Although serum is a very common specimen type, it comes with certain drawbacks. Most importantly, it depends on venous puncture and requires medical personnel for sampling. This is of particular importance in light of the limited healthcare access of patients with autoimmune diseases during the COVID-19 pandemic. Consequently, alternative sample matrices are being explored for the measurement of autoantibodies. Our study aimed to establish the feasibility of measuring autoantibodies in saliva samples using a novel and highly sensitive method for the detection of autoantibodies. (2) Methods: A total of 48 serum/saliva pairs were collected and tested using a novel particle-based multi-analyte technology (PMAT) system for the presence of a wide range of autoantibodies. (3) Results: A high level of correlation was observed between the results obtained with serum and saliva (Spearman's rho = 0.725). Study participants clearly preferred saliva over serum sampling as part of the usability assessment. (4) Conclusions: Saliva represents a promising alternative sample matrix for the detection of autoantibodies. The usability study showed a clear preference of saliva over serum as a sample matrix.

The Impact of Anti-SARS-CoV-2 Vaccine in Patients with Systemic Lupus Erythematosus: A Multicentre Cohort Study.

Vulnerable subjects, including systemic lupus erythematosus (SLE) patients, have been prioritised to receive anti-SARS-CoV-2 vaccines. Few data about the safety of these vaccines in SLE are available. The aim of our study is to investigate the safety of anti-SARS-CoV-2 vaccines in SLE. We included 452 SLE patients, referring to seven tertiary centres, who were immunised. A total of 119 (26%) reported side effects (SE) after the first and/or the second shot (the most frequent SE were fever, local reaction, fatigue, and arthralgia). Patients with constitutional symptoms and those on an immunosuppressive regimen (especially belimumab) showed more SE. In addition, 19 (4%) had a flare after the immunisation (flares classified by organ involvement: six musculoskeletal with constitutional symptoms, four renal, three cardio-respiratory, three haematological, two mucocutaneous). None of the patients needed hospitalisation and none died. Moreover, 15 required a transient increase in corticosteroids and four were treated with steroid pulses. One patient required an additional rituximab course. Anti-dsDNA, moderate/high DAS before vaccine, and belimumab were found more frequently in patients with disease flare. Anti-SARS-CoV-2 vaccines are safe in SLE patients, and they should be recommended in these patients, as the potential benefits widely outweigh the risk of SE. Treatment adjustment might be considered with the aim of minimising SE risk and flare.

Tailoring Tofacitinib Oral Therapy in Rheumatoid Arthritis: The TuTOR App

To support the management of rheumatoid arthritis (RA) patients treated with tofacitinib, we designed the TuTOR (tailoring tofacitinib oral therapy in rheumatoid arthritis) mobile app. The impact of the app on medical adherence was evaluated using a crossover design alternating a paper-diary and the TuTOR App. Twenty patients with RA (mean age at inclusion, 59 ± 13 years) were included in the study. A statistically significant decrease in DAS28 was observed since the first month of therapy (mean DAS28 at baseline, 3.9 ± 1 vs. 1° month 3.1 ± 1, p = 0.0016). Similarly, the numerical rating scale (NRS) of perceived activity of disease and subjective fatigue progressively decreased. No differences were reported in DAS28 or NRS between the TuTOR app and the paper-diary groups. A significant decrease was observed in HAQ during the follow-up (baseline 1.38 ± 1.11 vs. six months 0.83 ± 0.9;p = 0.01). When filling out the self-reporting questionnaires, most of the patients (82%) preferred the TuTOR App helping them to remember to take the pills. Furthermore, 82% of patients used the app regularly (vs. 53% for the paper diary). Three patients suspended tofacitinib due to gastrointestinal intolerance. Both digital and paper devices can help maximize adherence to therapy;however, the TuTOR app was preferred by the patients for its simplicity and immediacy.

Dietary Patterns at the Individual Level through a Nutritional and Environmental Approach: The Case Study of a School Canteen.

The public catering sector has important responsibilities in seeking a change toward more sustainable choices for many aspects related to the environmental impacts of their services. The environmental impact of production processes can be studied through life cycle assessment (LCA), which allows a greater awareness of choices and has rarely been applied to catering. In this work, we studied the impacts of two dishes (braised meat and cauliflower meatballs) in a school canteen, their impacts were studied using the daily energy requirement (expressed in kcal) as a functional unit. Global warming potential (GWP) and nonrenewable energy (NRE) were calculated starting from the supply of raw materials up to distribution. Electricity and the act of cooking the meatballs accounted for more than 60% of the measured impact in terms of GWP, whereas, less markedly, they dominated in terms of nonrenewable energy used. In the case of braised meat, the total impact was, however, attributable to the life cycle of the meat (between 60% and 76%) and the consumption of electricity (between 19% and 27%), whereas for all other factors, the contribution was never particularly high. Additionally, a discussion on the correct functional unit to be used proposed the environmental impact of different recipes as an additional criterion for nutritionists during the composition of the menu. An integrated system appears important for changing policies and behaviors and the application of LCA can be a tool capable of contributing to the construction of a holistic instrument of sustainability.

New Onset Biopsy-Proven Nephropathies after COVID Vaccination.

INTRODUCTION: To date, almost 7 billion doses of the different types of vaccine against SARS-CoV-2 have been administered worldwide. Although the severity of new cases of SARS-CoV-2 has progressively decreased, and the pressure on national health systems has declined, the development of de novo glomerular injuries has been suggested. METHODS: This study aimed to examine the patients who were hospitalized in our Unit between April and November 2021 and underwent renal biopsy for new-onset urinary abnormalities (UA) and/or renal impairment within 3 months of SARS-CoV-2 vaccination. RESULTS: We identified 17 patients who developed UA and/or renal insufficiency within 3 months of vaccination. Minimal change disease was the most common disease in our cohort (5 patients, 29.4%) followed by acute tubulointerstitial nephritis (TIN; 3 patients, 17.6%), membranous nephropathy (3 patients, 17.6%), and rapidly progressive IgA nephropathy (2 patients, 11.8%). The other 4 patients had a diagnosis of membranoproliferative glomerulonephritis (1 patient), systemic lupus erythematosus (1 patient), ANCA-associated vasculitis (1 patient), and tip-variant focal segmental glomerulosclerosis (1 patient), respectively. Eight out of the 17 patients (47.1%) developed acute kidney injury. Two patients with acute TIN had to start hemodialysis that was discontinued after 1 and 2 months, respectively, due to the recovery of renal function. All patients underwent treatment with corticosteroids and/or immunosuppressants. DISCUSSION: Although it is not possible to conclusively determine whether there is a causal relationship between SARS-CoV-2 vaccination and new-onset nephropathies, based on the appearance of UA and/or renal insufficiency shortly after vaccination, we hypothesize that the immune response to the COVID-19 vaccine may be a trigger of nephropathies. Therefore, our results highlight the need for pharmacovigilance. However, this report should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh the potential risks.

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

Clinical and peculiar immunological manifestations of SARS-CoV-2 infection in systemic lupus erythematosus patients.

OBJECTIVES: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with SLE remains unclear and data on clinical manifestations after infection are lacking. The aim of this multicentre study is to describe the effect of SARS-CoV-2 in SLE patients. METHODS: SLE patients referring to four Italian centres were monitored between February 2020 and March 2021. All patients with SARS-CoV-2 infection were included. Disease characteristics, treatment, disease activity and SARS-CoV-2-related symptoms were recorded before and after the infection. RESULTS: Fifty-one (6.14%) SLE patients were included among 830 who were regularly followed up. Nine (17.6%) had an asymptomatic infection and 5 (9.8%) out of 42 (82.6%) symptomatic patients developed interstitial pneumonia (no identified risk factor). The presence of SLE major organ involvement (particularly renal involvement) was associated with asymptomatic SARS-CoV-2 infection (P = 0.02). Chronic corticosteroid therapy was found to be associated with asymptomatic infection (P = 0.018). Three SLE flares (5.9%) were developed after SARS-CoV-2 infection: one of them was characterized by MPO-ANCA-positive pauci-immune crescentic necrotizing glomerulonephritis and granulomatous pneumonia. CONCLUSIONS: SARS-CoV-2 infection determined autoimmune flares in a small number of patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.

The role of antirheumatics in patients with COVID-19.

The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

Antiphospholipid Antibodies and Infection: Non Nova Sed Nove.

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.

OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.