EXCELLENT PROGNOSIS of RHEUMATIC MANIFESTATIONS FOLLOWING COVID-19 VACCINATION: 7 MONTHS FOLLOW-UP DATA

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.

SARS-COV-2 COURSE and OUTCOME in PATIENTS with SYSTEMIC AUTOINFLAMMATORY DISEASES (SAID) TREATED with IL-1 INHIBITORS and COLCHICINE

Background: The spread of COVID-19 had a strong impact in north-east Italy especially during 2020 and in the frst months of 2021. Patients affected by rheumatological disorders are at high risk of infections due to immunosuppressant therapies and a clear immunological imbalance. However, some anti-cytokines such as IL-1 inhibitors proved to be effective in curbing the cytokine storm, frequent feature of severe COVID-19. Objectives: We assessed the SARS-CoV-2 clinical course in 28 patients affected by autoinfammatory diseases, referring to the Autoinfammatory Outpatient Clinic of Padova University;in particular we observed if patients undertaking IL-1 inhibitors (group-1) had a diverse outcome compared to those not on anti-IL-1 drugs (group-2). Methods: Through telephone or e-mail consultancy, 28 patients (18 females, mean age 39.5±15), confrmed to have contracted COVID-19 between March 2020 and January 2022. Twelve patients (42.8%) were affected by periodic fevers (FMF/TRAPS), 10/28 (35.7%) had Adult-Onset Still's Disease, 3/28 (10.7%) had Undiffer-entiated Autoinfammatory Diseases, while 2/28 (7.1%) were affected by BehÇet Disease and one patient had Schnitzler Syndrome. 12 out of 28 patients (42.8%) were undertaking IL-1 inhibitors;8/28 (28.5%) were in therapy with colchicine;2 patients were in therapy with methotrexate and abatacept respectively, and 6/28 (21.4%) received no therapy. All were diagnosed with COVID-19 after molecular nasopharyn-geal swab performed either for the presence of symptoms or close contact with a positive subject. 5/28 patients had the infection after receiving the second vaccine shot, two after the booster dose. All the others had COVID-19 before the vaccine injection. GraphPad5 was used for statistical analysis and Fisher's test was applied. Results: COVID-19 clinical course was benign in 27 out of 28 patients (96.4%);a total of 29 infections were counted due to a case of re-infection;2 patients discontinued the therapy;all the others continued their medications (92.8%). Two patients (7.1%) of the entire cohort were hospitalized, one died. Regarding the major symptoms (fever ≥ 38 C°, cough/respiratory or gastro-intestinal symptoms) no difference was noticed between group-1 and group-2 (p=0.449);despite group-1 required less symptomatic therapy than group-2, the difference was not signifcant (p=0.471). Table 1 summarizes the clinical features exhibited by the patients and the therapies undertaken during the infection. Conclusion: Despite the low sample size, our study is of interest since it proves that the inhibition of IL-1 with both anakinra or canakinumab and the employment of colchicine, an important infammasome regulator, may curb the hyperinfammation typical of COVID-19. Given the promising results obtained with anti-IL-1 and colchi-cine in treating severe COVID-19, it is conceivable a 'protective' role of these drugs in preventing a massive cytokine release. Unsurprisingly, none of our patients but one, had a severe course or fatal outcome after SARS-CoV-2 infection.

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

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.

The amount of cytokine-release defines different shades of Sars-Cov2 infection.

The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: "mild",symbolized as a "drizzle" of cytokines, severe as a "storm", and critical as a "hurricane". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a "cytokine-release syndrome", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.