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Case report The Food and Drug Administration (FDA) provided emergency use authorization (EUA) for the Pfizer/BioNTech (BNT162b2) COVID-19 vaccine in December 2020. Implementation of COVID-19 mass vaccination efforts were implemented soon after. However, following the FDAs EUA, COVID-19 vaccine allergic reactions were reported. These findings led to concerns about vaccine hesitancy and the possible avoidance of future doses. The Texas Children's Hospital COVID-19 Vaccine Hypersensitivity Clinic was established in December 2020 to help address these concerns and to evaluate both pediatric and adult patients with immediate allergic reactions to the COVID-19 vaccines, as well as evaluating patients with polyethylene glycol (PEG) or polysorbate (PS) allergy. We present the case of an 18yo female who experienced anaphylaxis following her second Pfizer mRNA COVID-19 vaccine. The patient developed symptoms of generalized hives, chest tightness and dyspnea 17 minutes after receiving the Pfizer mRNA COVID-19 vaccine. She was treated in the emergency department with IM prednisone and PO diphenhydramine. Of note, in 2018, she had a similar response to her HPV9 vaccine (containing PS 80). Tryptase wasn't obtained at the time of her COVID-19 or HPV9 vaccine reactions, but she did have a baseline that was normal around 4ng/mL. Skin testing was performed to the following: PEG 3350, PS 20 and PS 80. Skin testing (skin prick and intradermal) were negative for PS20 and PS80. PEG 3350 skin prick was negative but methylprednisone acetate (PEG 3350) was positive at the 4mg/mL intradermal testing strength. She underwent a Miralax (PEG 3350) oral challenge. Within 20 minutes of ingesting 0.17grams PEG 3350 she developed an itchy macular rash on neck and upper chest, nausea and a globus throat sensation. She was treated with PO cetirizine and symptoms improved. Tryptase level was obtained 30 min after the start of her reaction and was 4ng/mL. Given the patient's reaction, she was advised to avoid PEG containing products and will return to undergo a graded-step challenge to the Janssen (J&J) COVID-19 vaccine. The prevalence of COVID-19 mRNA vaccine anaphylaxis and PEG allergies is rare. However, allergy referral is warranted in cases of immediate reactions to the COVID-19 vaccine or history of PEG or polysorbate allergies.
ABSTRACT
Background: During the initial rollout of COVID-19 vaccination in Singapore, the Ministry of Health (MOH) issued recommendations that patients with a history of any previous vaccine allergy be referred to an allergist for further review on suitability to proceed with mRNA-based COVID-19 vaccines. We review the evaluation of these patients with suspected vaccine allergies prior to receiving mRNA-based COVID-19 vaccines. Method(s): Between 8 April and 22 September 2021, 304 patients were evaluated prior to receiving the COVID-19 vaccinations. Of these, 63 (20.7%) patients with suspected immediate hypersensitivity reactions to non-COVID polysorbate-containing vaccines proceeded to have skin prick test (SPT) and Intradermal test (IDT) to polyethylene glycol (PEG)-3350, polysorbate 80 and polysorbate 20 containing products. Another 62 (20.4%) who reported delayed hypersensitivity reactions to polysorbate-containing vaccines proceeded to have direct inoculation (DI) of the Pfizer BNT162b2 vaccine under the supervision of an allergist. The remaining 242 (76.6%) finally assessed not allergic polysorbate-or tolerated previous non-polysorbate- containing vaccines were recommended to proceed with COVID-19 vaccinations at the community vaccination sites. 99 patients in the SPT/IDT and DI group completed a questionnaire-based survey to report any post vaccination reactions. (Figure 1) Results: Of 63 patients who underwent SPT/IDT, 2 (3.2%) with equivocal IDT tolerated both doses of the BNT162b2 vaccine without major allergic reactions. 61 (6.8%) patients with negative SPT/IDT and 62 (100%) in the DI group completed both doses of BNT162b2 vaccination without major reactions. Among those who completed the questionnaire survey, 13 (13%) reported reactions including non-specific rashes and mild urticaria/angioedema post first dose vaccine. All subsequently completed the second dose of the BNT162b2 vaccine following allergist review;with 8 (61.5%) reporting similar mild skin reactions. Conclusion(s): Majority of those with suspected reactions to polysorbate containing vaccines are able to tolerate the BNT162n2 vaccine which contains PEG-2000. Skin tests prior to mRNA COVID-19 vaccination is unnecessary. Those who report mild potentially allergic reactions after the first dose are able to tolerate the second dose of the BNT162b2 vaccine.
ABSTRACT
Background: Polyethylene glycols (PEGs) are hydrophilic polyethers widely used in pharmaceutical, cosmetic, food, and household products. PEG is usually safe and allergic reactions are rare, however according to literature, hypersensitivity is most likely underestimated and mild to life-threatening immediate-type hypersensitivity to PEG have been reported. PEG 2000 is an ingredient in some of the COVID-19 vaccines and is a possible cause of rare cases of adverse reactions to the vaccines that have been reported*. PEG hypersensitivity seems to depend on molecular weight (MW) and higher MW PEGs appear to be more allergenic. Based on this, we developed two ImmunoCAP PEG tests with different MW:s of PEG for measurement of anti-PEG specific IgE (sIgE) and specific IgG antibodies. Method(s): ImmunoCAP PEG 2000 and PEG 10000 Research Use Only (RUO) tests were developed according to conventional methods. As PEG is structurally related to polysorbates, a specific polysorbate 20 free washing solution was developed. The analytical characteristics of the ImmunoCAP PEG tests have been determined and an accelerated stability study has been performed. Result(s): The developed RUO ImmunoCAP PEG 2000 and PEG 10000 tests fulfilled internal standard RUO specifications using the polysorbate 20 free washing solution. Intra-and inter assay performance were evaluated at three concentrations from low to high on the sIgE measuring range (0-100 kUA/L). Overall results for intra-and inter assay performance were <=6.0 %CV and <=9.5 %CV, respectively. Anti-PEG IgG have been reported in human plasma samples with levels reaching up to 6.5 mug/mL (median 49.3 ng/mL). No anti-PEG IgG interference could be detected for these PEG tests when assayed with an anti-PEG IgG positive control in concentrations up to 6.5 mug/mL. An accelerated stability study indicated a shelf-life of two years for both PEG tests. Conclusion(s): Two ImmunoCAP PEG tests have been developed. These tests have been used as a complementary research tool to evaluate the risk for hypersensitivity reactions to PEG and to determine sIgE sensitization pattern in patient serum. In addition, studies have shown sIgE levels >0.1 kUA/L using these ImmunoCAP PEG tests for patients with a history of reactions to PEG together with positive skin prick testing. *It is important to understand that these reactions are extremely rare and should not discourage the general public from vaccination.
ABSTRACT
Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.
ABSTRACT
Background: The rapid spread and recurrent infections of SARS-CoV-2 has led to increased use and availability of at-home antigen testing, but widespread testing of antibodies against spike and nucleocapsid to monitor vaccine-induced immunity and exposure to the virus is lacking. Most serological tests require a serum sample from a venous blood draw, increasing risk of exposure to COVID-19 and limiting availability and scalability of testing for many patients. This is especially the case for individuals who are immunocompromised, such as those with inflammatory bowel diseases (IBD), which are frequently on medications that might alter their immune response and impact vulnerability to SARS-CoV-2. Use of easily acquired and stably stored dried fingerstick blood serves a promising specimen source for at-home, remote testing for SARS-CoV-2 antibodies. Aim(s): Validate the use of fingerstick blood (dried and then eluted) versus serum as a specimen for the measurement of quantitative spike and nucleocapsid antibodies to SARS-CoV-2 in a diverse cohort of healthy and immunocompromised patients. Method(s): Patients were consented and enrolled into the Pediatric Gastrointestinal Tissue, Stool, Saliva and Blood Registry prior to having an endoscopic procedure. Five mL of blood was obtained by venipuncture and 10 muL of fingerstick blood was collected and dried on a Neoteryx Mitra device. Blood was eluted from the Neoteryx Mitra samples in 200 muL of dilution buffer (1% BSA, 0.05% Tween-20, 140 mM NaCl, 50 mM Tris (pH 8.0), 0.025% sodium azide) and placed on an orbital shaker at a speed of 500 RPM for 3 h. Paired serum and fingerstick blood eluate specimens were run on the quantitative Roche Elecsys SARS-CoV-2 spike antibody assay and the qualitative Roche Elecsys SARS-CoV-2 nucleocapsid antibody assay. Linear regression were performed on each assay with exclusion of values that were above the upper limit of detection of the assay. Result(s): We observed an excellent correlation in both SARS-CoV-2 antibody assays when comparing fingerstick blood eluates and serum. The linear regression for the nucleocapsid antibody assay had a slope of 15.5, intercept of 4.05, and R2 of 0.92, indicating that a Neoteryx value of 1.00 COI (cut-off index) equates to a serum value of 19.6 COI. The linear regression for the spike assay had a slope of 13.6, intercept of 953, and R2 of 0.95, indicating that a value of 1,000 U/mL from a fingerstick sample equates to a serum value of 14,544 U/mL. Conclusion(s): These data demonstrate that fingerstick blood collected on Neoteryx Mitra devices can be used as a specimen source in Roche Elecsys SARS-CoV-2 antibody assays to calculate the serum levels of spike and nucleocapsid antibodies. This can serve as a platform to remotely and reliably monitor the durability of antibody responses to natural infection with and immunization against SARS-CoV-2 in patients. Chart comparisons of nucleocapsid (top) and spike (bottom) protein antibody levels detected via remote fingerstick collection (Neoteryx, x-axis) and venous blood serum (y-axis).
ABSTRACT
Background: In order to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) an active approach is necessary. On December 2020 the commercialization of the COVID-19 vaccines was made. In Spain the first one to arrive was Pfizer-BioNtech vaccine. Initially, several reports of anaphylactic reactions due to the vaccine in the USA and in the UK were reported, which lead to an early recommendation to avoid the administration in patients with allergic history. The objective of this study is to describe and characterize the allergenic profiles of patients attended in our clinic for allergy testing to prevent reactions with the COVID-19 vaccine. Method: The allergological profile of 85 patients diagnosed with previous history of allergic disorders was analysed between January 18th and March 16th 2021. The allergological study included skin-prick test with polyethylene glycol (PEG), Tween 20, Tween 80, and COVID-19 vaccine (Pfizerâ), together with latex and other allergens when necessary. After the double dose of vaccine was completed, a follow up was done by telephone. Results: Risk stratification and approach is exposed in figure 1. Clinical and allergological characteristics of 85 patients are shown in table 1. Out of them, 88.2% had an allergic comorbidity and 48.2% had drug allergy. The reason for consultation was in 92.9% due to their allergic history, 76.5% were referred from the Occupational Health Service, and 80.6% of the patients have had previous vaccination with other anti-infective vaccines without reactions. Also, table 1 shows the prick-test results with COVID vaccine an its excipients, without any positive result. 70.7% of our population has completed the vaccination. Only 9 patients had a possible allergic reaction to the first dose, 8 of them had cutaneous and the remaining had respiratory symptoms. Out of these 9 patients, 6 had their second dose without any symptoms. Conclusion: None of the patients studied showed a positive test for neither the components of the vaccine nor the vaccine itself. More studies are required with a larger sample size to reach final conclusions. (Table Presented).