ABSTRACT
BackgroundThe main systemic sclerosis (SSc) manifestations are skin thickening, microangiopathy and ischemic changes in tissues, fibrotic damage to the lungs, heart, kidneys, and digestive system, arthritis, and myopathy. Acute phase reactants (APR) like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect inflammation activity in various inflammatory conditions. Ferritin is a protein bound to iron;low serum ferritin indicates iron deficiency and/or anemia. Instead, high ferritin levels are associated with inflammatory and non-inflammatory conditions such as dermatomyositis, pulmonary fibrosis, lupus, systemic COVID-19, vasculitis, tissue damage, thromboembolic complications, and metastatic cancer. The possible role of ferritin in SSc as APR is unclear.ObjectivesWe aimed to assess whether ferritin levels can reflect the severity of SSc and predict the outcome.Methods241 files of SSc patients with information on serum ferritin level (ferritin over 300 mg/dL is considered elevated) who visited the Rambam Rheumatology Institute in the years 2004-2021were used for retrospective analysis. Patients' demographic, clinical, laboratory, imaging, and respiratory function data were collected from electronic hospital files. Statistics included Student's T-test, Pearson's chi-squared test, and Kaplan-Meier curve;statistical significance was determined as p<0.05.Results36 patients (FerEl-SSc) had elevated ferritin values;the rest (n=205) represented the second group (FerNor-SSc). Significant differences were seen in gender (male 44.4% - 15.6%), disease duration (4.56 - 7.7 years), modified Rodnan skin score (12.3 - 6.9), as well as in incidence of lung (65.7% - 38.7%), heart (51.4% - 21.1%), and renal (28.6% - 5.9%) involvement. Increased ferritin correlated with elevated ESR, CRP, creatinine, creatine kinase, troponin, and reduced hemoglobin, impaired pulmonary function tests and reduced left ventricular ejection fraction on echocardiography. Patients with elevated ferritin had a significant increase in mortality rates (52.8% and 35.1%) and non-significant reduction in survival.ConclusionOur study demonstrated that ferritin has a potential as a sensitive marker for SSc severity in term of skin thickening, vital organ complications, and mortality. The ferritin test is simple and inexpensive, it can add to the complex SSc assessment and contribute to treatment decision-making in complicated SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundThe 3rd booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3rd and 4th boosters against the omicron variants, among AIRD pts are scarce.ObjectivesWe aimed to assess the effect of the 3rd and 4th booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs.Methods212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3rd booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3rd booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5th outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3rd booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first.ResultsThe 3rd booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4th booster and 18 the 5th booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3rd booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4th booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3rd booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004).There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2nd vaccination.ConclusionDespite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3rd booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Background: AIRD patients (pts) may be more susceptible to severe COVID19. Objectives: To determine the risk factors for severe COVID19 and the effect of vaccinations among AIRD pts followed at dedicated rheumatology clinics. Methods: At the onset of the pandemic, we established a national registry of AIRD pts, diagnosed with COVID19, based on voluntary reporting by the treating rheumatologist. 12 centers from Israel participated in the study. COVID19 was confrmed by a positive SARS CoV2 PCR. The indications for PCR testing were clinical symptoms or close contact with an infected person. Severe illness was defned by SpO2 <94% in room air, respiratory rate of >30 breaths/min, PaO2/FiO2 <300 mm Hg, or lung infltrates >50% on imaging. The registry included demographic data, AIRD diagnosis and duration, visceral involvement, co-morbidities, immunomodulatory treatment, date of diagnosis and severity of COVID19 disease, management, complications, duration of hospitalization, the dates of the mRNA vaccinations, lab results and outcome. We analyzed data from 1.3.2020 to 30.11.2021 Results: During the study period we experienced 4 outbreaks of COVID19 infection. Initially social distancing, followed by a lockdown were imposed. The low number of cases led to relaxation of the measures. Two more severe outbreaks followed, which triggered 2 new lockdowns. The 3rd outbreak ended almost 2 months after vaccination started (BNT162b2 mRNA COVID19 vaccine). From March 1st 2020 to April 30, 2021, 298 AIRD pts (70.8% females, mean (SD) age 53.3(15.3)) with confrmed COVID19 infection were included. 43.3%(129) had visceral involvement due to the AIRD. 58.7%(175 pts) were on conventional synthetic disease modifying drugs (csDMARDs), 44.6% (133) on biologic/targeted DMARDs and 40% (120) on prednisone. Almost 2/3 of pts had at least one comorbidity. In a multivariate logistic regression analysis age, AIRD with pulmonary involvement, diabetes and treatment with prednisone, mycophenolate mofetil or JAK inhibitors were associated with hospitalization. Older age, renal and vascular involvement due to the AIRD, and congestive heart failure were associated with higher mortality. The 4th outbreak occurred 6 months after the introduction of vaccines, with spreading of the delta variant: 110 AIRD pts with COVID19 were recorded. Demographic data, clinical AIRD's characteristics, immunomodulatory treatment and comorbidities were similar to the previous outbreaks. However, during the 4th outbreak, the proportion of pts with severe COVID19, the hospitalization and mortality rate were signifcantly lower as compared to the frst 3 outbreaks (15% vs 24%, 27% vs 53%, 6.7% vs 9.1%, respectively). Among COVID19 pts, 25% received a 3rd vaccine dose (booster), 56% contracted infection more than 5 months after the 2nd vaccine dose and 24% were unvaccinated. Most of the pts who received the booster contracted the disease within a week of vaccination. The odds ratio for hospitalization in vaccinated pts compared to unvaccinated was 0.11 (0.01-0.63 95% CI, p=0.041) in those vaccinated within the previous 1-5 months, and 0.38 (0.21-0.67 95% CI, p=0.001) in those vaccinated more than 6 months ago. 9 pts died, 5 were more than 6 months after the 2nd mRNA vaccine, 2 were unvaccinated and 1 patient received the booster on the same day of COVID19 diagnosis. Conclusion: Before the vaccination campaign, the hospitalization and mortality rate in our cohort were similar to the data reported by other registries. COVID19 tends to be more severe, with increased mortality in patients with active AIIRD and visceral involvement (pulmonary, cardiac, renal), advanced age and co-morbidities. The delta outbreak occured 6 months after the implementation of vaccinations and was associated with signifcantly lower hospitalization and mortality rates, despite the increased aggressiveness of the variant. Vaccination of AIIRD pts with 3 doses of mRNA vaccines protects from severe COVID19 disease, hospitalization, and death.
ABSTRACT
Background: Previous studies proved that mRNA vaccinations against SARS CoV2 induced signifcant humoral responses in AIRD patients (pts). However, the humoral response was blunted in pts treated with CD20 depleting antibodies. There are limited data regarding the long-term outcome of the humoral response and the contribution of the booster vaccine, in immunosuppressed AIRD pts. Objectives: To assess the long-term outcome of the humoral response to mRNA vaccine against SARS CoV2, in AIRD pts treated with immunomodulating drugs, and the contribution of the booster vaccination. Methods: Consecutive pts treated at the Rheumatology Institute at Rambam Hospital who received their frst SARS-CoV-2 (Pfzer) vaccine were recruited to the study, at their routine visit. The visit included AIRD activity assessment and questioning regarding vaccine side effects. We performed serology test 4-6 weeks and 24 weeks after receiving the second dose of vaccine. Pts who received the booster (3rd vaccine) were invited for serology tests 4-8 weeks afterwards. The immunomodulating treatment was not modifed, either before or after the vaccination. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay based on a chemi-luminescent microparticle immunoassay (CMIA) on the ARCHITECT ci8200s-ystem from Abbott. This assay is measuring IgG antibodies against the spike receptor-binding domain (S-RBD) of the virus. The test was considered positive above 50 AU/ml. Results: 262 pts (mean age(SD) 57(13), disease duration 11.2(7.4), were recruited. The cohort included 152 pts with infammatory joint disease, 26 pts with systemic lupus erythematosus, 62 pts with other connective tissue disease and 22 pts with vasculitis;27 % received csDMARDs only, 35%-b/tsDMARDs only, 30%-combined therapy (csDMARDs+b/tsDMARDs) and 26% received steroids. 225 pts (86%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, IQR 58-29499). 37 (14%) pts had negative tests, 23 (62.2%) of them were rituximab treated. The IgG levels correlated with the medication used to treat the AIRD, the patients' age but not with the type of the AIRD (Figure 1). 24 weeks afterwards, the median IgG level dropped to 282 AU/ml and 15% of the pts with previous seropositive tests became negative. The booster administration (Pfzer) signif-cantly augmented the humoral response (median 8328 AU/ml, IQR 375-40000). De novo serologic response was observed in 10 out of 37 pts (4/23 rituximab treated pts). The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The AIRD remained stable in all pts following all three vaccinations. Conclusion: Although the vast majority of AIRD pts developed a substantial humoral response following the administration of the second dose of the Pfzer mRNA vaccine against SARS CoV2 virus, the humoral response signifcantly declined 24 weeks afterwards. An enhanced response was obtained after the third booster vaccination. Only minor side effects were reported and no apparent impact on AIRD activity was noted. Notably, 62% of the non-responders were treated with B cell depleting agents.
ABSTRACT
Background: The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce. Objectives: To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in Israel Methods: At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO2 <94% in room air, respiratory rate of ≥30 breaths/min, PaO2/FiO2 <300 mm Hg, or lung infiltrates ≥50% on chest imaging. The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021. Results: During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease). We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1). Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/ tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis -6, systemic lupus erythematosus -2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone≥10 mg. All patients who died had at least 2 comorbidities. Conclusion: The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded.