ABSTRACT
Background: Allergic reactions to COVID-19 vaccines have raised concerns, particularly as repeated doses are required. Skin tests with vaccines excipient were found to be of low value whereas the utility of skin tests with the whole vaccine is yet to be determined. Objective(s): we set to evaluate a panel of skin tests and outcomes of subsequent doses of immunization among subjects that suffered an immediate allergic reaction to the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Method(s): In a prospective cohort study during December 27th-2020 to February 22nd-2021 Individuals with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center in israel, underwent risk assessment using an algorithm that included a detailed questionnaire department. Patients were considered to be at high risk for allergic reactions if thery either had: (1) prior anaphylactic reaction to any drug or vaccine, (2) multiple drug allergies, (3) multiplemallergies, or (4) mast cell disorders, as were patients who were deferred by their GP or local allergist or the immunization team from vaccination in the regular setting because of concerns about allergic. reactions. This high-risk group was referred to be immunized with 2 hours of observation by a dedicated allergy team. Result(s): Of the 429/8102 individuals who applied to the COVID-19 referral center and were defined as "highly allergic", 304 (70.8%) were female, mean age was 52 +/- 16 years. This "highly allergic" group was referred to immunization under medical supervision. Following the 1st dose of the BNT162b2, 420/429 (98%) had no immediate allergic event, 6/429 (1.4%) developed minor responses and 3/429 (0.7%) had anaphylactic reactions. During the study period, 218/429 "highly allergic" patients received the 2nd dose, of which 214/218 (98.1%) had no allergic reactions while 4 patients had minor allergic reactions. Other immediate and late reactions were comparable to the general population except for delayed itch and rash that were more common among allergic patients. Conclusion(s): The rate of allergic reactions to BNT162b2 vaccine, is higher among allergic patients, particularly in a sub-group with high-risk history. In this study we showed that the vast majority of patients with a history of allergic diseases and particularly "highly allergic" patients can be safely immunized. Utilizing an algorithm that can be implemented in different medical facilities and include a referral center, a risk assessment questionnaire and a setting for immunization under medical supervision of "highly allergic" patients. Further studies are required to define more specific risk factors for allergic reactions to BNT162b2 vaccine.
ABSTRACT
IntroductionIn the era of COVID-19 pandemic, data on safety and efficacy of anti-COVID vaccines in SLE patients is needed and scarce. Belimumab is a monoclonal antibody directed at BAFF, an essential cytokine in B cell survival, though it does not impair efficacy of some traditional vaccines. Thus, the aim of our study was to assess immunogenicity and safety of BNT162b2 Pfizer mRNA vaccine in SLE patients treated with Belimumab.MethodsSLE patients treated with Belimumab for at least 6 months in the Sheba Medical Center were included in this study. All were recommended to receive the BNT162b2 COVID-19 mRNA vaccine according to Ministry of Health recommendations, and thereafter to perform a serologic test for CoV-2 IgG 2–6 weeks after receiving the 2nd or 3rd doses. Clinical data included demographics, SLE treatments, adverse effects to the vaccine as well as SLEDAI scores performed 2 weeks before receiving 1st dose and 6 to 8 weeks after receiving 2nd and 3rd doses of the vaccine.ResultsOur cohort included 17 patients, 15(88.2%) were females, median age was 50±14.2 years, and disease duration was 12±10.57 years. Median Belimumab treatment time was 6±2.5 years. In our cohort 2/17 received only 2 vaccine doses as thereafter the suffered mild COVID-19 infection, while 15/17 patients received 3-doses. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the 3rd dose. Vaccination was well tolerated with minimal adverse events and no disease flares (e,g. SLEDAI 7.7±5.19 and 7.82±5.2 before vaccination and post 3rd dose respectively).ConclusionsImmunization with 3 doses of BNT vaccine is safe and efficacious for SLE patients treated with Belimumab. Only following the 3rd dose immunogenicity of SLE patients in this cohort mounted to 90%, thereby approximating the general healthy population. Assessment of seroconversion and consideration of subsequent boosters’ vaccine should be considered for SLE patients treated with Belimumab.
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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: 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.