Background The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. MethodsWe did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case-control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. Findings Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55-76] years vs 57 [49-67] years; p=0•0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2•8 [95% CI 1•3-6•1]; p=0•031) and obesity (11 [17%] vs 1 [2%]; OR 11•0 [1•3-83•4]; p=0•0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78•8 years [IQR 75•3-81•3] vs 65•5 years [53•3-74•0]; p=0•0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case-control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died...

Multisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infection, but other possible etiologies should be ruled out for definitive diagnosis. On the clinical side, along with the multi-system involvement, myocarditis with heart failure and shock is the most striking feature. Capillary leak is another fundamental feature of MIS-C. In fact, shock and hemodynamic compromise in MIS-C can occur also in the absence of laboratory evidence of myocardial inflammation, with preserved cardiac function and rapid reversibility. Since the first observations of MIS-C patients, it was evident that there is a delay between the peak of adult cases of Coronavirus disease 19 (COVID-19) and the MIS-C peak. Moreover, SARS-Cov2 isolation in children with MIS-C is not always possible, due to low viral load, while positive serology is far more commonly observed. These observations lead to the interpretation of MIS-C as a post-infectious disease. Although the exact pathogenesis of MIS-C is far from being elucidated, it is clear that it is a hyperinflammatory disease with a different inflammatory response as compared to what is seen in acute SARS-CoV-2 infection and that the disease shares some, but not all, immunological features with Macrophage Activation Syndrome (MAS), Kawasaki Disease (KD), Hemophagocytic Lymphohistiocytosis (HLH), and Toxic Shock Syndrome (TSS). Different mechanisms have been hypothesized as being responsible, from molecular mimicry to antibody dependent enhancement (ADE). Some evidence has also been collected on the immunological profile of patients with MIS-C and their difference from COVID-19. This review is focused on critical aspects of MIS-C clinical presentation and pathogenesis, and different immunological profiles. We propose a model where this hyperinflammatory disease represents one manifestation of the SARS-CoV2 spectrum in children, going from asymptomatic carriers to the post-infectious MIS-C, through symptomatic children, a low number of which may suffer from a severe infection with hyperinflammation (pediatric Hyper-COVID).

BackgroundBelimumab is a human monoclonal antibody that inhibits soluble B lymphocytes stimulator (BlyS) and represents the only biological drug approved for Systemic Lupus Erythematosus (SLE) (1). Belimumab is effective in reducing disease activity, number of flares and blocking damage progression (2,3). Pooled data derived from clinical trials reported a reduction of anti-dsDNA,analysed by ELISA, anti-cardiolipin (aCL) and anti-Sm and anti-ribosomal protein antibodies (2,4). No data were published on anti-beta2glycoprotein I (GPI) antibodies and other antiENA specificities.ObjectivesOur aim was to analyse the effect of Belimumab therapy on high avidity anti-dsDNA, aCL, anti-beta2GPI, and other relevant anti-ENA specificities.Methods50 patients with active SLE (mean SLEDAI-2K score: 7,18;SD:3), with a mean age of 39 years (SD:11) and mean follow-up of 13 years (SD: 7,8) were enrolled. Sera were collected at Belimumab starting (T0) and every 6 months until 24th month. Disease activity index (SLEDAI-2K) was collected at every timepoints. High avidity anti-dsDNA were detected by radioimmunological method, anti-ENA, anti-cardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI) were analysed by ELISA.ResultsAt baseline 86% of sera were positive for anti-dsDNA, 50% for anti-ENA, 20% for aCL and 28% for anti-beta2GPI. Anti-dsDNA became negative in 21%, anti-beta2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Among anti-ENA, 6/10 (60%) anti-ribosomal and 3/17 (17.6%) anti-Sm positive sera became negative. A significant decrease of anti-dsDNA and anti-beta2GPI IgM titers were observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-ribosomal showed a significant titre decrease at T6 and T12, with seroconversion to negative at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during time. A significant correlation between anti-dsDNA and anti-ribosomal titre, and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titer ratio (value/value T0) were found.ConclusionBelimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-beta2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and improvement of disease activity.References[1] Stohl W, et al. Nat. Biotechnol. 2012; 30: 69-77.[2] Ginzler EM, Wallace et al. J Rheumatol 2014; 41:300-9.[3] Iaccarino et al. Arthritis care Res 2017; 69: 115-123.[4] Stohl W, et al. Arthritis Rheum 2012; 7: 2328-37.Disclosure of InterestsIlaria Cavazzana: None declared, Rajesh Kumar: None declared, Salvatore Panaro: None declared, Chiara Pozzari: None declared, Roberta Ottaviani: None declared, Micaela Fredi: None declared, Silvia Piantoni: None declared, Laura Andreoli: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Franco Franceschini: None declared

Background:The World Health Organization recommends that infants should be exclusively breastfed until the age of 6 months. The aim of this study was to assess the ratio of breastfeeding patients with Rheumatic Diseases (RD) and to identify possible causes of its discontinuation.Objectives:The aim of this study was to assess the ratio of breastfeeding patients with Rheumatic Diseases (RD) and to identify possible causes of its discontinuation.Methods:This study was embedded in the P-RHEUM.it register, as a nationwide prospective cohort study collecting data of pregnancies in inflammatory RD. Pregnancies, enrolled until the 20th week of pregnancy, are followed from pregnancy until 6 months postpartum. At baseline, sociodemographic parameters, obstetric history, comorbidities are reported. During pregnancy, the course of maternal disease, development of foetus and complications are reported. After delivery, the pregnancy outcome, data on lactation and child development are collected.Results:From May 2018 to May 2020 data of 349 patients were available. Data on lactation were available in 44 pregnancies. Two months after delivery 37 were continuing breastfeeding (n=26) or mixed feeding (n=11), while 7 were using formula feeding. Among patients using formula feeding 2 had a diagnosis of rheumatoid arthritis (RA), 1 of juvenile idiopathic arthritis, 1 of undifferentiated arthritis (UA), 1 of anti-phospholipid syndrome (APS), 1 of vasculitis and 1 of systemic lupus erythematosus. The reasons of formula feeding were the following: 2 for agalactia, 2 for personal preferences, 3 for drug-related concerns (1 for physician’s decision in a patient with APS; 2 for maternal concerns about drugs in patients with RA and UA treated respectively with Adalimumab and Tocilizumab). At 6 months 30 continued breastfeeding (n=23) or mixed feeding (n=7) and 14 formula feeding. The reasons of formula feeding were available in 9 patients: 3 for agalactia, 2 for personal preferences, 2 for physician’s decision in a patient with APS and in a patient positive for anti-phospholipid antibodies; 2 for maternal concerns about drugs.Conclusion:Preliminary data of this prospective study demonstrate a high percentage of breastfeeding/mixed feeding after delivery and after 6 months among women with RD. Drug related concerns are the main reason of discontinuation of breastfeeding, although medication results compatible with lactation. Using our results, strategies supporting patients with RD whishing to breastfeed may be developed.References:[1]Carina Gotestam Sporken et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016.[2]Sammaritano et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and muscoloskeletal diseases, Arthritis Rheumatol. 2020.Acknowledgements:Authors would like to thank SIR study center and all patients who accepted to partecipate to our studyDisclosure of Interests:None declared