ABSTRACT
Background: Vaccinations against SARS-CoV-2 represent a fundamental tool in controlling the pandemic. To date, data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis, are limited. Objectives: In this study we aimed at evaluating the safety of anti-SARS-CoV-2 vaccines in a multicentric cohort of patients with systemic vasculitis. Methods: Patients with systemic vasculitis from two Rheumatology centres who had received anti-SARS-CoV-2 vaccine were retrospectively examined. The primary outcome was to evaluate, in this multi-centric cohort, the occurence of a disease fare after the administration of the vaccine, defned as development of clinical manifestations related to vasculitis with a concomitant increase in serum infammatory markers. As a secondary outcome we aimed at evaluating, in a monocentric cohort of patients with vasculitis, the occurrence of adverse events (AEs) following vaccine administration compared to healthy controls (HC). Results: We examined 111 patients with systemic vasculitis (n=69 female, n=42 male), with a mean age of 64.3 (± 13) years. Sixty had ANCA-associated vas-culitis (AAV), fourty-two had Giant-Cell Arterities (GCA), five had Periarteritis Nodosa, four had Takayasu's arteritis. One-hundred and five patients received a mRNA vaccine and six a viral vector one. A disease fare occurred in only 2 patients (1.8%) after the frst dose of a mRNA vaccine: both had AAV (microscopic poliangioitis) and developed a pulmunary disease fare (respiratory failure requiring hospitalization and treatment with high-dose glucocorticoids). Of note, one of these patients had multiple previous comorbidities, including a severe COPD. Multivaried analysis, adjusted for age and sex, performed in a single monocentric cohort of patients with systemic vasculitis [n=60 (39 AAV, 21 GCA), 37 female, 23 male, mean age 71 (± 12.5) years] demonstrated a statistically sig-nifcant higher frequency of AEs in vasculitis patients compared to HC (p=0.015) after the frst dose of vaccination. No signifcant differences in the frequency of AEs in vasculitis patients compared to HC after the second dose were detected. All the AEs were mild in both groups (malaise was the most frequently reported);no serious AEs were reported. Conclusion: Our data show a very low incidence of disease fares after the administration of anti-SARS-CoV-2 vaccines in patients with systemic vasculitis. Patients with systemic vasculitis seem more prone to develop mild AEs after the frst dose of the vaccine. Taken together, this data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.
ABSTRACT
Background: The spread of COVID-19, the lockdown, the limited access to care reevaluated the role of tele-consultation and self-assessment. Objectives: Our aim was to evaluate in a cohort of Rheumatoid Arthritis (RA) patients treated with JAK-inhibitors (JAKi): the self-assessed disease activity during lockdown, the lockdown impact on fatigue, anxiety, depression and the prevalence of Covid-19. Methods: We enrolled RA patients treated with baricitinib or tofacitinib. At baseline (BL) and follow-up we collected: patients' demographic data, composite disease activity indices (CDAI, DAS28CRP), global assessment (PGA), pain visual analogue scale (VAS), FACIT (functional assessment of chronic illness therapy) and a self-rating scale for disease impact on anxiety and depression (Zung-A/D). Patients were instructed on how to perform self-assessment through video-material and fulfilled the online form of Rheumatoid Arthritis Impact of Disease (RAID)1 and RA Disease Activity Index (RADAI). To capture the pandemic effect, we compared patients in different status (remission, low, moderate and high-disease activity) at the last in-person visit (preCoV) through the DAS28CRP and CDAI, to the tele-health visit (THV), measured by the RAID. BL and pre-CoV ZUNG-A, ZUNG-D, FACIT questionnaires were compared with the online results during the pandemic. Exposure, tests and symptoms of Covid-19 were recorded. Data were expressed as mean±standard deviation or median(IQR) according to distribution. Results: Twenty patients (median age 58.2±11.9 and mean disease duration 153.5 ± 112.7 months) were treated with tofacitinib and 27 with baricitinib. The median time-lapse between the pre-CoV visit and the THV was 12 (IQR 4) weeks. DAS28CRP and CDAI significantly decreased from BL to pre-CoV visit. During the last in-person visit, 21 patients (48.83%) were in remission, 9 (20.93%) in low disease activity;according to the RAID, 15 (31.91%) and 7 (14.89%) patients were respectively in remission and low disease activity during the THV (Table A). PGA and pain significantly decreased from BL to pre-Cov visit but worsened during the lockdown (Table A). FACIT remaining stable during THV. At THV, we detected a significant improvement of anxiety from BL (Zung-A) and a tendency to lower depression scores compared to BL (Table A). JAKi showed a good safety profile considering Covid-19 symptoms, none of the patients was diagnosed with SarsCoV2 infection. Conclusion: This is the first study on virtual assessment in RA patients treated with JAKi. The unique social experiment of the pandemic impaired the clinical response already achieved before the lockdown, without a collateral worseling of FACIT, anxiety and depression.
ABSTRACT
Background: Antimalarials have been associated with QT prolongation in COVID19 patients but are generally safe in patients with rheumatologic disease. Objectives: Aim of the study was to compare the prevalence of QTc prolongation between COVID19 and Systemic Lupus Erythematosus (SLE) patients treated with hydroxychloroquine (HCQ). Methods: We included consecutive patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab and patients taking HCQ for SLE. A prolonged QTc was defined as an increase in QTc intervals ≥60 ms (compared with baseline) or as a QTc of ≥500 ms. Results: We enrolled 58 COVID19 patients (median age 70.5 years, IQR 25). HCQ, without or with azithromycin, was given to 26 (44.8%) and 15 patients (25.9%), respectively;17 (29.3%) had not received either drug. The median baseline QTc was 432 (IQR 36) and prolonged QTc was observed in 15 (26%) patients (12 QTc≥500 ms and 3 patients ΔQTc≥60 ms). We didn't find significant differences in QTc prolongation among the three treatment groups. Baseline QTc (OR 111.5) and D-dimer (OR 78.3) were independently associated to QTc prolongation. Compared to the 50 SLE patients (median age of 38.5 years, IQR 22), chronically treated with HCQ, patients with COVID19 showed significantly longer QTc (p < 0.001) (Table 1). Conclusion: This is the first study demonstrating that, differently from COVID19 patients, patients with SLE are not susceptible to HCQ-induced long QT syndrome and arrhythmia. The combined arrhythmogenic effect of SARS-CoV-2 infection and HCQ could account for the excess of QTc prolongation and fatal arrhythmias described in patients with COVID19.
ABSTRACT
Background: Since the beginning of the SARS-CoV-2 outbreak, antiphospholipid antibodies (aPL), a known thrombotic risk factor, have been studied in COVID-19 patients, in whom thromboembolic events have been associated with poor prognosis. To date, the pathogenetic role of aPL and the trend over time is still unknown. Objectives: Aim of the study was to investigate whether aPL positivity was correlated with thrombosis in COVID-19 patients and whether it was a transient or persistent. Methods: We included all consecutive COVID-19 patients hospitalized at Policlinico Umberto I, Sapienza University of Rome from April 1, 2020 to June 7, 2020. In these patients, serum levels of anti-cardiolipin (aCL) IgM, IgG, IgA, anti-β2glycoprotein I (aβ2GPI) IgM, IgG were measured by enzyme-linked immunosorbent assay (ELISA) and Lupus Anticoagulant (LA) was detected with coagulatory tests in patients not in treatment with anticoagulant drugs. Results: Five out of 73 (6.8%) patients resulted positive for aCL IgM, 3 of them also tested positive for aβ2GPI IgM. aCL IgA were tested positive in 14 out of 46 patients (30.4%). Overall 18 patients resulted positive for at least one test. Seven (9.6%) patients developed thrombotic events during hospitalization, 3 of them resulting positive for aPL (Table 1. below). We observed that patients showing double positivity for aCL IgM and aβ2GPI IgM had a likelihood positive ratio of 6.3 for thrombotic events (p=0.012) and a likelihood positive ratio of 4.9 for increased D-dimer levels (p=0.027). aCL IgA, the most prevalent aPL in this cohort, was not associated with thrombosis. Of the 18 aPL positive patients, 5 died, 3 were lost to follow-up, and 10 were tested on a second occasion at least 12 weeks, two patients confirmed positivity without clinical signs suggestive of APS. Conclusion: These results suggest that double positivity for aCL and aβ2GPI IgM increases the risk of thrombosis in COVID-19 patients, unlike aCL IgA. APL positivity may be persistent and it is advisable to monitor it over time.
ABSTRACT
Background: Conflicting results have been published regarding the risk of infection with SARS-CoV-2 and development of severe COVID-19 among patients affected by rheumatic musculoskeletal diseases (RMDs). [1-4] Taking into account the lack of effective drugs to treat the COVID-19 and despite the burdensome and costly lockdown measures adopted to counteract the spread of SARS-CoV-2, effective and safe vaccines appear reasonably to be the best strategy for fighting the virus. [6] Before vaccines availability, several reports showed that a non-negligible proportion of subjects, among the general population or within specific categories, would have refused vaccination against COVID-19 once possible;[6, 7] data on vaccination hesitation among patients with RMD are not available yet. Objectives: This study aimed to evaluate the attitude of patients with RMDs to vaccination against SARS-CoV-2 and explore the factors which may influence it. Methods: During the first weeks of Europe vaccination campaign, we proposed an online survey to Italian adult patients with RMDs followed up in the Rheumatology Unit. All patients fulfilled the most recent classification criteria for each disease. HCs were recruited using a “best friend” system. The informed consent was collected for all participants. The questionnaires included the following items: demographic features, presence of comorbidities, educational level, and ongoing therapy. The individual's perception of the COVID-19 vaccination, as well as the willingness to receive a COVID-19 vaccination with targeted questions was properly assessed. For the statistical analyses, Mann-Whitney and Chi-square tests were used. To account for baseline clinical differences among RMD-patients and controls, multivariable logistic regression analysis was used;covariates were selected according to a clinical criterion. The hypothesis that willingness for COVID-19 vaccine varied in specific subgroups of patients was tested using interaction terms at logistic regression analysis. All statistical tests were performed using the RStudio graphical interface and all tests were two-sided with a significance level set at p<0.05. Results: We provided an online survey to 830 adult RMD-patients and 370 healthy controls (HCs). Overall, 626 RMD-patients and 345 HCs completed the survey. Patients with RMDs were less willing to receive a COVID-19 vaccination compared to HCs (Odds Ratio (OR) 0.24, 95% CI 0.17 -0.34, p<0.0001) despite they perceived themselves as at higher risk both to get infected (OR 11.3, 95% CI 8 -15.9, p<0.0001) and develop a severe COVID-19 (OR 11.06, 95% CI 7.8 -15.6, p<0.0001) and even if they had been vaccinated for influenza and pneumococcus more frequently than controls (OR 1.60 95% CI 1.18 -2.16, p=0.002;OR 2.23, 95% CI 1.34 -3.73, p=0.002). However, our results reveal that RMD-patients are more willing to change their minds if properly informed by the rheumatologist (OR 3.08, 95% CI 2.19 -4.34, p<0.0001) in comparison to controls. Conclusion: The results of our study indicate for the first time that patients with RMDs are less willing to receive COVID-19 vaccination compared to the general population, despite perceiving themselves as at higher risk of getting infected with SARS-CoV-2 and develop severe COVID-19. However, our data underscored a meaningful aspect: patients with RMDs may change their attitude to COVID-19 vaccination if properly informed about risks and benefits by their trusted specialist. The results of this study encourage the entire rheumatologist community to become more committed to patient education, increasing their willingness to COVID-19 vaccine, which is the most promising strategy to protect them from the virus.