Safety and Efficacy of Sars-Cov-2 Vaccination in 1237 Patients with Primary Sjogren Syndrome

Objectives. To investigate the safety and efficacy of SARS-Cov-2 vaccination in a large international cohort of patients with primary Sjogren syndrome due to scarcity of data in this population. Methods. By the first week of May 2021, all Big Data Sjogren Consortium centers had been contacted and asked for Registry patients to be included in the study if they had received at least one dose of any SARS-CoV-2 vaccine. The in-charge physician asked patients about local and systemic reactogenicity, using a pre-defined electronic questionnaire to collect epidemiologic data, COVID 19 vaccination data, and COVID 19 vaccination side effects. Adverse events were defined as those reported by the patient at the site of injection within 7 days from vaccination (reactogenicity) as local adverse events, systemic symptoms as systemic side effects, and postvaccination AEs of special interest related to SS as SS flares. Results. The vaccination data of 1237 patients (1170 women, with a mean age at diagnosis of primary SjS of 50.5 13.2) were received. A total of 835 patients (67 percent) reported any adverse event, including local (53 percent) and systemic (50 percent) AEs. Subjective symptoms (63%) were the most common local AEs, followed by objective signs at the injection site (16%) and general symptoms were the most commonly reported systemic AEs (46 percent), followed by musculoskeletal (25 percent), gastrointestinal (9 percent), cardiopulmonary (3 percent), and neurological (2 percent). People under 60 years old had a higher risk of developing AE after vaccination (OR 2.48, CI 95 1.89-3.27 percent), as did those with low systemic SS activity (OR 1.62, CI 95 1.22-2.15) and those who received mRNA vaccines, according to a multivariate analysis (OR 1.57, CI 95 percent 1.12- 2.18). The risk of developing systemic AEs was also higher in women (OR 2.85, CI 95 percent 1.60-5.2346), White people (OR 1.73, CI 95 1.14-2.65), and those who received a deficient vaccination regimen (OR 1.78, CI 95 1.12-2.88 percent). In addition to 141 (11%) patients who reported a significant worsening/exacerbation of their pre-vaccination sicca symptoms as a result of post-vaccination SS flares, 15 (1.2%) patients (13 women, mean age at vaccination 41.9 years) reported active involvement in the glandular (n=8), articular (n=7), cutaneous (n=6), pulmonary (n=2), and peripheral nervous system (n=1) domains as post-vaccination systemic flare. All side effects and flares subsided within 1-3 weeks, with no lasting effects or deaths. In terms of vaccination efficacy, breakthrough SARS-CoV-2 infection was confirmed after vaccination in three (0.24 percent) patients, all of whom recovered completely, and positive anti-SARS-Cov-2 antibodies were detected in approximately 95 percent of vaccinated SjS patients, according to data available. Conclusions. SARS-CoV-2 vaccination in patients with primary SjS, like other vaccines with adequate response and no safety signals, raised no concerns about the vaccine's efficacy or safety.

Sars-Cov-2 Infection in 898 Patients with Sjogren's Syndrome: Characteristics Associated with Poor Outcomes

Objectives. To determine characteristics associated with a more severe COVID-19 outcome in people with Sjogren's disease (SJD). Methods. People with SJD and COVID-19 reported to two international registries (Sjogren Big Data Consortium and COVID-19 Global Rheumatology Alliance) from March 2020 to October 2021 were included. An ordinal COVID-19 severity scale was defined: (1) not hospitalized, (2) hospitalized with no ventilation, (3) hospitalized requiring non-invasive ventilation, (4) hospitalized requiring invasive ventilation, and (5) death. Odds ratios (OR) were estimated using a multivariable ordinal logistic regression model adjusted for age, sex, comorbidities and anti-rheumatic medications included as covariates. Results. A total of 898 people with SJD were included (825 (91.8%) women, mean age SARS-CoV-2 infection diagnosis: 55.5 years), including 652 patients with primary SJD and 246 with other associated systemic rheumatic diseases. 33.9% were hospitalized, 14.5% required ventilation, and 4.3% died. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.05), male sex (OR 1.81, 95% CI 1.10 to 2.92), two or more comorbidities (OR 2.99, 95% CI 1.92 to 4.67;vs none), baseline therapy with corticosteroids (OR 2.04, 95% CI 1.20 to 3.46), immunosuppressive agents (OR 2.09, 95% CI 1.30 to 3.38) and B-cell depleting agents (OR 5.38, 95% CI 2.77 to 10.47) were associated with worse outcomes (reference for all medications: hydroxychloroquine only). Conclusions. More severe COVID-19 outcomes in individuals with Sjogren's are largely driven by demographic factors and baseline comorbidities. Patients using immunosuppressants, especially rituximab, also experienced more severe outcomes.

THE BURDEN of POST-SARS-COV2 VACCINE COMPLICATIONS and NEWLY DIAGNOSED IMMUNEMEDIATED INFLAMMATORY DISEASES

Background: Local and systemic reactions have been observed after all vaccines for SARS-CoV-2 but in the majority of cases, symptoms are mild and self-limiting. However, evidence on more severe clinical scenarios, requiring admission to hospital or referral to outpatient clinics after the administration of SARS-CoV-2 vaccines has accrued. This also includes newly diagnosed diseases, such as cardiovascular and immune-mediated infammatory diseases (IMID). Objectives: We aimed at quantifying the burden of post-vaccine hospital admissions/referrals and of newly diagnosed IMID. Methods: Clinical records of patients referred to our Internal Medicine institution (both inpatients and outpatients) between February and June 2021 were retrospectively assessed. Subjects having received one or more doses of any of the EMA-approved SARS-CoV-2 vaccines within the previous 30 days were included. Subjects with a previous diagnosis of IMID were excluded. Results: Our cohort included 99 patients, 45 females and 54 males, with a mean age of 64 years and a median of 3 comorbities (range 0-7). Eighty-eight patients (89%) required admission to the Internal Medicine ward while 11 were referred to the outpatient clinic. 68 (69%) of patients received the vaccine BNT162b2, 16 (16%) the ChAdOx1 nCoV-19, 9 (9%) the mRNA-1273 and 6 (6%) the Ad26. COV2.S. Twenty-seven (27%) subjects developed symptoms after the frst vaccine dose with a mean latency of 2 days (median=0 indicating symptom onset on the day of the vaccine administration). Twenty-four (24%) subjects developed symptoms after the second dose with a mean latency of 4 days (median 1 day). All the other subjects did not develop symptoms within the week after the vaccine and were admitted for reasons apparently unrelated to vaccine administration. The number of presenting complaints ranged between 1 and 4 with 87% of subjects presenting with 1 or two coexisting complaints. Gastrointestinal manifestations were the most frequent being the presenting complaint in 31 (31%) of patients followed by severe fatigue/appetite loss in 19 (19%) of subjects, fever in 18 (18.2%) and neurological manifestation in 16 (16%) of subjects. A temporal and causal association with the SARS-CoV-2 vaccine was identifed since all other known causes for these manifestations were ruled out. No in-hospital deaths were observed and 19 (19%) patients were diagnosed with a new onset IMID (Table 1). The clinical picture of these subjects was not signifcantly different from that of patients without a confrmed IMID and neither were demographic features. No association with the type of vaccine was observed. Conclusion: Our data show that post-vaccine newly diagnosed IMID may represent a challenge in clinical practice and it seems that no demographic or clinical feature is able to predict their onset. A multidisciplinary cooperation and registry data are needed in order to reliably estimate and defne the impact of SARS-CoV-2 vaccinations on new onset IMID.

Mise à jour des recommandations EULAR sur l’utilisation des thérapies immunomodulatrices dans la prise en charge de la Covid-19

Introduction Les formes sévères de COVID-19 comportent à une hyperinflammation systémique intense ;ce qui a justifié des essais thérapeutiques avec des immunomodulateurs régulièrement utilisés chez les patients atteints de maladies systémiques auto-immunes ou inflammatoires Depuis février 2021 où les premières recommandations EULAR sur l’utilisation de thérapeutiques immunomodulatrices dans le COVID-19 ont été publiées [1], de nouveaux essais thérapeutiques ont été réalisés ce qui rend nécessaire une mise à jour ces recommandations. Matériels et méthodes Selon les procédures standardisées de l’EULAR [2], les résultats d’une revue de la littérature systémique réalisée jusqu’au 15 décembre 2020 puis mise à jour jusqu’au 14 juillet 2021 incluant tous types d’études ont été présentés à un groupe de travail multidisciplinaire composé d’experts internationaux comprenant des rhumatologues, des immunologistes translationnels, des hématologues, des pédiatres, des patients et des professionnels de la santé. La mise à jour des recommandations a été discutée et votée par l’ensemble du panel d’experts sur la base des résultats présentés, principalement des essais randomisés contrôlés (ECT) sur différents traitements immunomodulateurs. Résultats La mise à jour comprend deux principes généraux et dix recommandations. Les recommandations concernent uniquement la prise en charge des patients présentant des formes de COVID-19 modérées à sévères ou critiques, faute de preuves suffisantes avec très peu d’ECT concernant les patients asymptomatiques et ceux avec des formes légères de la maladie. Les molécules suivantes ont montré une efficacité dans le traitement de formes modérées à sévères ou critiques du COVID-19. L’association de glucocorticoïdes et de tocilizumab est bénéfique dans les cas de COVID-19 nécessitant une oxygénothérapie et dans les cas critiques de COVID-19. L’utilisation d’inhibiteurs de Janus kinase (baricitinib et tofacitinib) et peut-être d’Ac anti-GM-CSF est prometteuse dans les mêmes populations. Les anticorps monoclonaux anti-SARS-CoV-2 et l’utilisation de plasma convalescent pourraient trouver une application dans les phases précoces de la maladie et dans certains sous-groupes de patients immunodéprimés. D’autres immunomodulateurs comme l’hydroxychloroquine, la colchicine ou l’anakinra n’ont pas démontré leur efficacité sur la mortalité et ou sur l’aggravation clinique (évolution vers une détresse respiratoire), quel que soit le stade de la maladie. Conclusion Un nombre grandissant d’ECT soutiennent l’efficacité de l’association de glucocorticoïdes et d’autres agents immunomodulateurs tels que le tocilizumab dans le traitement de formes modérée à sévère et critique du COVID-19. De plus, certaines études en cours pourraient confirmer l’efficacité potentielle d’autres approches thérapeutiques comme les inhibiteurs de JAK ou les Ac anti-GM-CSF. L’implication des rhumatologues, en tant qu’experts des maladies inflammatoires et auto-immunes systémiques et des traitements immunomodulateurs est nécessaire dans le design des nouveaux essais cliniques et dans l’élaboration de nouvelles recommandations pour la prise en charge du COVID-19.

Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: Data from two italian covid-19 units

Background: The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation and a wide range of imaging findings, depending on disease severity and time course. The pathophysiology is complex, involving immune and hematologic systems, epithelial cells and vascular system and to date reliable biomarkers aimed at stratifying patients and predicting worse outcomes have not been identified Objectives: The aim of this study was to describe clinical, serological and CT imaging features of a cohort of patients with COVID-19 pneumonia and identify possible relationships between the variables and disease outcomes (admission to intensive care unit (ICU) and/or death). Methods: We evaluated hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement. Clinical and serological records of patients admitted to two COVID-19 Units in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively collected. Results: Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR=14.5, 95% CI=2.3-90.9, p=0.004), the presence of septal thickening (OR=8.2, 95% CI=1.6-40.9, p=0.011) and the presence of mediastinal lymph node enlargement (OR=12.0, 95% CI=1.1-127.5, p=0.039) independently of age and gender. Conclusion: We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender, but not with disease outcomes (admission to ICU/death). The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.