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Introduction: Prior to colonoscopy, it is well understood that patients must undergo bowel cleansing. Based on the type of laxative, colonoscopy preparations fall into two categories - polymer-based formulas (PEG) and saline-based formulas (NaP). Both types of bowel preparations are deemed to be relatively safe and part of routine practice. However, we describe the rare case of an ulcerative colitis (UC) flare due to the bowel preparation formula. Case Description/Methods: A 29-year-old female with diagnosis of UC, presently in clinical and biochemical remission on oral mesalamine, contracted COVID-19 and had reactivation of UC symptoms. After being on budesonide tablets and rectal foam for two months, patient achieved clinical remission, and a surveillance colonoscopy was performed which revealed normal colon and terminal ileum except mild congestion in the cecum (Figure A). Pathology revealed unremarkable mucosa in the entire colon except for chronic active colitis in the cecum. Immediately following this colonoscopy, the patient started to experience another severe UC flare requiring hospitalization. The patient's laboratory work-up was normal except for an elevated fecal calprotectin (1710). Stool infectious work-up was negative and the patient denied any NSAID or antibiotic use. The patient underwent a repeat colonoscopy which revealed severe Mayo 3 pancolitis (Figure B) in comparison to a stable colonoscopy a few weeks prior. It was revealed that for her initial colonoscopy, she had used SUPREP bowel prep kit. On prior colonoscopies she had used MiraLAX bowel prep with no adverse effects. During hospitalization, the patient was started on biologic therapy with good effect. Discussion(s): There are no clear guidelines on appropriate bowel preparation formula for the inflammatory bowel disease (IBD) population. Sufficient literature exists to confirm that NaP can irritate the intestinal mucosal wall. Moreover, numerous animal experiments have employed dextran sodium sulfate for chemical induction of intestinal inflammation to mimic UC flares in humans [1]. Thus, it can be surmised that because SUPREP ingredients contain sodium sulfate, the potential for UC flare is higher. It is pertinent for practitioners to be aware of the possible rare adverse effects of saline-based formulas, especially when treating the IBD population.
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Introduction: Subacute thyroiditis is a self-limiting post-viral inflammatory disorder occurring in 3 phases (hyper-, hypo-, and euthyroidism) Post-vaccine thyroiditis has also been reported, but is rare. Case Description: A 36-year-old Emirati female presented to our clinic with generalized fatigue, mild to moderate vague neck pain, intermittent palpitations, and loss of appetite 2 weeks after receiving her first dose of Pfizer-BioNTech mRNA vaccine against COVID-19. Clinical examination findings and laboratory test results were consistent with subacute thyroiditis. Patient is a mother of 5 healthy children, youngest is breast-fed infant (11 months old). There was no history suggestive of postpartum thyroiditis and no family history of thyroid dysfunction. Physical examination at initial visit showed mild tachycardia, and a normal blood pressure. She weighed 66 kg. Thyroid function tests revealed a suppressed TSH of 0.011 muIU/mL, high Free T4 of >100 pmol/l), and Free T3 FT3 of 29.6 pmol/L. Both TSH receptor antibodies, and Thyroid antibodies (TPO) were negative. Thyroid scintigraphy showed decreased uptake in both lobes. Thyroid ultrasound showed hypoechoic heterogeneous echotexture of the thyroid gland with vascular conglomerate and micro-calcification, along with normal sized reactive lymph nodes at sternal angle. Symptoms aggravated through the next week;patient dropped 3kg of her body weight and her palpitations increased, with a recorded resting heart rate between 120-130 beats/min. TSH decreased to 0.001muIU/mL while FT4 remained high, with an improvement to 90 pmol/L. Subsequently, the patient started to regain weight. Palpitations improved within a month. She developed a biochemically hypothyroid picture followed by clinical and biochemical euthyroidism after one more month. Second dose of the vaccine was uneventful. Last evaluation was 10 months later;TSH, FT3 and FT4 were all in normal range, acute-phase reactants were completely normal and in complete remission. Discussion(s): The exact mechanism for post-vaccination subacute thyroiditis remains unknown, vaccine adjuvants may induce diverse autoimmune and inflammatory reaction. Subacute thyroiditis has rarely been reported with other COVID-19 vaccines contains no Polyethylene glycol (PEG). A possible cross-reactivity between thyroid cell antigens and spike protein of the coronavirus produced by mRNA vaccines might be responsible. Further research is needed to investigate the incidence of subacute thyroiditis in COVID-19 pandemic days.Copyright © 2023
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense RNA virus responsible for COVID-19, requires a set of virally encoded nonstructural proteins that compose a replication-transcription complex (RTC) to replicate its 30 kilobase genome. One such nonstructural protein within the RTC is Nsp13, a highly conserved molecular motor ATPase/helicase. Upon purification of the recombinant SARS-CoV-2 Nsp13 protein expressed using a eukaryotic cell-based system, we biochemically characterized the enzyme by examining its catalytic functions, nucleic acid substrate specificity, and putative protein-nucleic acid remodeling activity. We determined that Nsp13 preferentially interacts with single-stranded (ss) DNA compared to ssRNA during loading to unwind with greater efficiency a partial duplex helicase substrate. The binding affinity of Nsp13 to nucleic acid was confirmed through electrophoretic mobility shift assays (EMSA) by determining that Nsp13 binds to DNA substrates with significantly greater efficiency than RNA. These results demonstrate strand-specific interactions of SARS-CoV-2 Nsp13 that dictate its ability to load and unwind structured nucleic acid substrates. We next determined that Nsp13 catalyzed unwinding of double-stranded (ds) RNA forked duplexes on substrates containing a backbone disruption (neutrally charged polyglycol linker (PGL)) was strongly inhibited when the PGL was positioned in the 5' ssRNA overhang, suggesting an unwinding mechanism in which Nsp13 is strictly sensitive to perturbation of the translocating strand sugar-phosphate backbone integrity. Furthermore, we demonstrated for the first time the ability of the coronavirus Nsp13 helicase to disrupt a high-affinity nucleic acid-protein interaction, i.e., a streptavidin tetramer bound to biotinylated RNA or DNA substrate, in a uni-directional manner and with a preferential displacement of the streptavidin complex from biotinylated ssDNA versus ssRNA. In contrast to the poorly hydrolysable ATP-gamma-S or non-hydrolysable AMP-PNP, ATP supports Nsp13-catalyzed disruption of the nucleic acidprotein complex, suggesting that nucleotide binding by Nsp13 is not sufficient for protein-RNA disruption and the chemical energy of nucleoside triphosphate hydrolysis is required to fuel remodeling of protein bound to RNA or DNA. Our results build upon structural studies of the SARS-CoV-2 RTC in which it was suggested that Nsp13 pushes the RNA polymerase (Nsp12) backward on the template RNA strand. Experimental evidence from our studies demonstrate that Nsp13 helicase efficiently remodels a large high affinity protein-RNA complex in a manner dependent on its intrinsic ATP hydrolysis function. We proposed that this novel biochemical activity of Nsp13 is relevant to its role in SARS-CoV-2 RNA processing functions and replication. It was proposed that Nsp13 facilitates proofreading during coronavirus replication when a mismatched base is inadvertently incorporated into the SARS-CoV-2 genome during replication to reposition the RTC so that the proofreading nuclease complex (Nsp14-Nsp10) can gain access and remove the nascently synthesized nucleotide to ensure polymerase fidelity. Our findings implicate a direct catalytic role of Nsp13 in protein-RNA remodeling during coronavirus genome replication beyond its duplex strand separation or structural stabilization of the RTC, yielding new insight into the proofreading mechanism. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Background: The diagnosis of drug allergy requires a previous medical history suggestive of a Drug Hypersensitivity Reaction (DHR). DHRs caused by vaccines are rare (< 1/100.000 doses) and are mainly due to excipients. At the beginning of the COVID-19 vaccination, occasional cases of severe reactions were reported in patients with allergy history. This warning led to an increased demand for allergy testing to evaluate pre-vaccination risk assessment, especially due to the refusal of allergic patients to receive the vaccine. Method(s): Twenty patients were evaluated between May to July 2021, referred for allergology study prior to receiving the vaccine against COVID-19. All patients tested had allergy history. Skin tests were performed with the available excipients of the COVID-19 vaccine: polyethylene glycol (PEG-1500, 10% prick ROXALL), polysorbate 80 (tween 80 prick 0.04 -ID 0.004 mg/ml), and trometamol (prick 1 -ID 0.1 mg/ml). A telephone follow-up was subsequently performed to assess tolerance to the vaccine. Result(s): The median age of the patients was 54.5 years and ninety percent were female. (Table 1) The most frequent allergy history was adverse drug reactions (ADRs) in 18 patients (90%), followed by bronchial asthma (35%), rhinitis (25%), food allergy (25%), and dermatitis (15%). 12 patients (60%) had multiple allergic diseases. The drugs implicated in these ADRs were beta-lactam antibiotics (40%), NSAIDs (20%), radiographic contrast media (15%), and vaccines (15%). Skin tests with the excipients studied were negative in all cases. Subsequently, the COVID-19 vaccine was administered in 16 patients (80%). Six patients (30%) reported side effects expected from the vaccine and no DHRs were described. Although vaccination was recommended to all patients after the study, 4 patients (20%) refused the administration. Conclusion(s): Patients with atopic history do not require an allergology study prior to the administration of the COVID-19 vaccine. Exceptionally, it may be necessary if the patient has a history of suspected DHRs to the excipients involved. The previous allergology assessment did not prevent refusal of vaccination in 20% of the patients. (Table Presented).
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Background: Polyethylene glycol (PEG) and polysorbate are two commonly used excipients in cosmetics, therapeutics, and processed foods. They are used not just to stabilize and preserve but also to influence the pharmacokinetics and bioavailability of the active ingredients of these products. Numerous reports have described patients with recurrent urticaria self-reporting multiple unrelated products hypersensitivities. We aim to describe a case series of sensitization to PEG in patients with recurrent urticaria and its implications to the currently available COVID-19 vaccines in Malaysia. Method(s): Data of all patients during the peak vaccination period (March 2021 -May 2021) who had positive intradermal test to surrogate PEG and polysorbate 80 were retrieved and analyzed. They were tested with PEG 4000 (macrogol), PEG 400 (Systane Ultra eye drop) and polysorbate 80 (Tween 80). Result(s): A total of eight patients were skin test positive to PEG and/ or polysorbate 80. The mean age was 35.1 +/- 10.5 years. Only one patient was male. Everyone reported history of multiple product reactions with recurrent urticaria as the major symptom. Majority (75%) had multiple unrelated products hypersensitivities. Four of them had urticarial reactions after the first dose of mRNA vaccine. Two patients were skin test negative to the lower molecular weight PEG 400. Cross sensitization between PEG 4000 and polysorbate 80 was 100%. All patients were subsequently inoculated with two doses of inactivated virus COVID-19 vaccine without any serious sequalae. Conclusion(s): The validity of skin testing towards PEG is not yet clear. Nonetheless it is a promising tool in diagnosing PEG sensitization in selected patients reporting recurrent urticaria with multiple unrelated products. Pretesting of this select group may be considered before the inoculation of PEG-containing COVID-19 vaccine.
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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.
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Background: The SARS-COV- 2 vaccination campaign has massively mobilized the allergists' community to screen patients deemed at risk for the SARS-COV- 2 vaccines. To describe data regarding the management of medical calls regarding the allergic risk for the SARS-COV- 2 vaccination, amongst French allergists. Method(s): A questionnaire-based survey was launched on the AdviceMedica platform (a platform of medical advice exchange between peers) between July and October 2021 (including two reminders). Result(s): Fifty-four allergists answered the survey. Three quarters of the responders were full-time allergists. Overall, 42% and 35% had an exclusive hospital or private practice, respectively. Allergists were mostly contacted by telephone (96.3%) and e-mail (79.6%), by general practitioners (92.6%) or physicians practicing in vaccination centers (88.8%) (median of vaccine related medical calls: 10 per week (Q25-Q75: 7-20, range (2-300). Allergists favored in-person visits rather than teleconsultations (85.2% vs. 61.1%). Allergy testing was prescribed for suspicions of allergy to polyethylene glycol (84.4%) or other vaccines and non-identified drugs (64.4%). Half of the responders (29, 53.7%) could perform vaccination and four (13.7%) declared reactions during vaccination. The responders used several tools in taking their clinical decision: exchanges with peers from the AdviceMedica platform (40.4%), advice from tertiary university hospital allergy units (25%), recommendations of the French Society of Allergy (17.3%). The three most frequent drawbacks that the allergists encountered were: having a hard time adding supplementary patient visits within optimal delays (three quarters of the responders), the reluctance expressed by the physicians requiring the advice and by the patients (two thirds) and the fact that the learnt society recommendations were deemed not to cover many on-field situations (one third). The major benefits from screening were estimated to be the lack of allergy contraindication to vaccination (88.7%) and the increased visibility of the allergist's role (69.8%). Conclusion(s): This survey put numbers on the management of screening patients deemed at risk for the SARS-COV- 2 vaccination amongst French allergists. Peer exchange was the most frequent tool in taking a clinical decision.
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Background: Covid 19 is a global epidemic. One of the most important steps in the fight against this epidemic is vaccination. mRNA vaccines are used in vaccination in our country. Among the additives in the vaccine, the substance with the highest allergenic risk is polyethylene glucose (PEG). There are different molecular weights of PEG. Another additive that has a high risk of cross-reaction with PEG as an additive is POLISORBAT 80. Skin tests with drugs containing PEG and POLISORBAT 80 and, if available, tests with vaccines are instructive. Among the drugs containing PEG: Moxifloxacin tablet, ciprofloxacin tablet, Amoxicillin clavulanic acid tablet;Medicines containing polysorbate include: Omalizumab vaccine, Mepolizumab vaccine. The results of the skin test with PEG-containing methylprednisolone (DEPO-MEDROL) and POLYSORBAT-containing triamcinolone (KENACORT-A) in order to be evaluated in terms of vaccine in our 2 patients who had multiple drug sensitivities before were shared. Method(s): Case 1: 33 y, F *There are diagnoses of urticaria and angioedema. Urticaria 30 minutes after taking aspirin, levofloxacin, cefdinir tablet;5 minutes after taking ciprofloxacin tablets, he has anaphylaxis. *Applies before Biontec vaccine. *The patient had a history of anaphylaxis with PEG-containing ciprofloxacin. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *The patient for whom Biontec vaccine was not recommended received Synovac vaccine without any problems. Case 2: 52 years, F * He has a diagnosis of urticaria. 5 minutes after general anesthesia and local anesthesia;The patient who had cardiac arrest 3 times was evaluated. The patient, who had Synovac for 2 times without any problems, wanted to have the 3rd dose of Biontec vaccine. *Tested with general -local anesthetic agents. *Ciprofloxacin skin tests are negative;Urticaria plaques developed after 30 minutes of 1/4 tb in oral provocation. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *Biontec vaccine is not recommended. Result(s): A safer vaccination is ensured by testing with additives in Covid 19 vaccines. Conclusion(s): Drug additives should also be kept in mind in patients with multiple drug allergies.
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Objectives: In this study, we developed angiotensin-converting enzyme 2 (ACE2)-specific, peptide-derived 68Ga- and 18F-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Our current efforts are focusing on broader dissemination of ACE2-targeted PET radiotracers based on chelation of [18F]AlF enabling advanced murine and potentially human studies. Method(s): A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga and 18F-AlF to generate the corresponding peptide radiotracers (68Ga-NOTA-PEP). The most potent 68Ga and 18F-AlF DX600 derivatives were subsequently studied in a humanized ACE2 (hACE2) transgenic model. Result(s): Cyclic DX-600-derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga and 18F-AlF, and the biodistribution of both tracers was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. The biodistribution of both tracers was similar, with apparent blocking observed in the lungs using the 18F-AlF peptide that needs to be verified via additional experiments. Conclusion(s): NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga or 18F-AlF chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine-organs known to be affected in SARS-CoV-2 infection. Blocking studies using the 18F-AlF labeled correlate showed modulation of PET signals in the normal lungs. These results suggest that 68Ga-NOTA-PEP4 or the 18F-AlF correlate could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2-infected murine models and COVID-19 patients.Copyright © 2023 Southern Society for Clinical Investigation.
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Background: Since the introduction of COVID-19 vaccines, many reports have focused on adverse reactions. However, there is no global agreement on how to manage those patients. We aim to assess the management of adverse reactions by an immunoallergology department and its outcomes. Method(s): Retrospective analysis of the patients sent to our centre from January to October 2021 for adverse reactions to a COVID-19 vaccine, and who were considered ineligible for a 2nd dose by general practitioners. We collected data on the reported reactions, allergological study and outcomes. Result(s): 123 patients with adverse reactions were included (77% women, n = 95), mean age 55 years-old (min 12;max 92). Pfizer/ BioNTech Vaccine was inoculated in 64 patients (52%);Moderna in 15 (12%);AstraZeneca in 44 (36%). 65 patients (53%) presented symptoms compatible with allergic reactions: 86% (n = 56) with mucocutaneous symptoms, mainly urticaria-like lesions and/or angioedema;17% (n = 11) with suspected anaphylaxis and 5% (n = 3) with Steven-Johnson Syndrome. 19 patients performed skin testing with: PEG2000 (n = 17);polysorbate 80 (n = 15);COVID-19 vaccines (n = 21). Four patients had at least one positive test. 58 patients (47%) presented with non-allergic reactions. They showed great variability of symptoms. Most mild: 47% reported non-specific symptoms (such as malaise, headache, myalgia, fever, or fatigue) and 26% reported local reactions on the inoculation site. Some severe: 6 with deep vein or pulmonary thrombosis, 4 with myocarditis, 2 with stroke or myocardial infarction, and 1 with VITT. Patients with positive skin tests or severe previous reactions (n = 36, 29%) were referred for an alternative vaccine. Those with suspected allergic reaction but negative skin tests were premedicated with antihistamines before the 2nd dose. Follow-up showed: of the 81 patients (66%) who received an additional dose, 25% (n = 20) reported an adverse reaction, which was mild, and no case of anaphylaxis was reported. 16 (13%) refused a 2nd dose, and for 26 (21%) the information could not be obtained. Conclusion(s): The intervention of an allergologist had a significant positive impact on vaccination rates, with 2/3 of patients being reclassified as eligible for a 2nd dose. Allergological study and intervention identified vaccine-allergic patients and guided the decision on vaccine change and premedication, which resulted in a considerably lower number of adverse reactions to the 2nd dose, or at least its severity.
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Background: Delayed-type cutaneous adverse reactions (DCARs) are potential adverse reactions induced by COVID-19 vaccinations. Objective(s): To investigate the immune pathomechanism of COVID-19 vaccination-related DCARs. Method(s): We conducted a prospective observational study on patients with COVID-19 vaccine-DCARs and tolerant subjects. Serum immune molecules and high-parameter blood cell analysis were analyzed.In vitro lymphocyte activation test (LAT) was performed to evaluate the causative allergens of COVID-19 vaccines for DCARs. Result(s): We enrolled 103 patients with COVID-19 vaccine-DCARs. Patients suffered from DCARs mainly after the first vaccination dose (75.7%). Compared to the tolerant controls, patients with DCARs showed significantly higher serum levels of IL-4, IL-6, IL-8, IL-17A, IL-18, IFN-gamma, IP-10, MIG, granulysin, PARC and TARC(P=3.40x10-5-0.028). High-parameter flow cytometric analysis revealed significant increased CD4+Th2, CD4+Th17, CD4+Th22, CD4+LAG-3+, CD4+CD103+Trm, Tfr, CD8+CXCR3+, CD8+Tc2, CD8+Tc17 and CD8+CTLA4+cell populations relative to total DCARs and specific phenotypes(P=0.001-0.042). In vitro LAT assays measuring IFN-gamma, granulysin, and granzyme B showed that patients with AZD1222-DCARs were significantly reactive to polysorbate 80 and spike protein;BNT162b2-DCARs were significantly reactive to polyethene glycol(PEG) 2000, and spike protein;while mRNA-1273-DCARs were significantly reactive to PEG 2000, tris and spike protein(P<0.05). Conclusion(s): We demonstrated a distinct immune response related to variable clinical phenotypes involved in the immune mechanism of COVID-19 vaccines-DCARs. In vivo LAT assays showed that COVID-19 vaccines excipients and spike protein were potential major components related to the COVID-19 vaccines-induced DCARs.Copyright © 2023
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Background: COVID-19 vaccines contain additives such as Polyethylenglycol-2000 (PEG2000;mRNA vaccines) or Polysorbat 80 (vector vaccines), which have been described previously as culprits for anaphylactic events. Method(s): This retrospective study included 46 individuals, who were referred to the Allergy Center at the Depart. of Dermatology, University Hospital Linz with suspected allergic reactions to the first COVID-19 vaccine dose with either mRNA or vector-based vaccines. Patients underwent detailed anamnesis, clinical examination and in most cases skin prick testing using pure additive substances (PEG -different molecular weights, Polysorbate 80). Result(s): Out of 46, 7 patients' reactions were classified as possibly anaphylactic and graded according to Ring & Messmer. Forty patients out of 46 were assessed with skin prick tests for potential allergens in COVID-19 vaccines. Only one patient showed an immediate positive prick test to PEG2000. Second-dose vaccination with mRNA or vector-based vaccines were tolerated well in all patients, including the individual with a positive skin prick test against PEG2000. Conclusion(s): The currently available COVID-19 vaccines have an overall low allergic potential and may be administered safely in patients with suspected allergic reactions to the first dose.
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Background: Covid-19 viral infection affects strongly the populations in the world by the level of morbidity, mortality and the economic impact. A worldwide vaccination program was developed since the end of 2020 to limit the propagation of the virus and the development of variants. In USA and Europe the risk of an allergic reaction is estimated to be 1.31 (95 % CI, 0.90-1.84) per million vaccine dose. The excipients are considered to be the most probable cause of IgE-mediated allergic reactions: PolyEthylene Glycol (PEG) for the Moderna and the Pfizer-BioNTech vaccines and Polysorbate 80 (P80) for the Astra Zeneca and the Johnson & Johnson. P80 presents clinical cross-reactivity with PEG. Patients with a history of severe allergic reaction to PEG or P80 should avoid the vaccination. However, some of them strongly wanted to be vaccinated because their accumulated risk factors for severe infection. Method(s): To 4 severely PEG/P80 allergic patients (grade 3 of anaphylaxis), we proposed a desensitization protocol (7 steps in 90 min + 60 min of observation) with the Pfizer-BioNTech vaccine. Each injection was performed alternately in the deltoid muscle (SC for 2 treated by apixaban) every 15 min. Two patient received all the injections in the same arm due to insufficient lymphatic drainage post mastectomy. The protocol was repeated 1 month and once again 6 months later for the second and the booster doses respectively. One patient didn't received the last one because she was meanwhile moved in palliative treatment. We followed the modification of their immunological status. All patients took a premedication with bilastine 20 mg and montelukast 10 mg (without PEG/P80) 24 h and 3 h before each protocol. Result(s): No patient developed adverse nor allergic reaction after the successive vaccinations. Conclusion(s): We c an p ropose adesensitization protocol to the COVID-19 Pfizer-BioNTech vaccine to patients with severe hypersensitivity to PEG/P80. The desensitization is well tolerated and followed by an increase of specific antibodies and an evolution of antibody level like patients who received the total dosis (0.3 ml) in one injection. (Figure Presented).
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Case report Background: P olyethylene g lycol ( PEG) a llergy i s g enerally c onsidered a contraindication to COVID-19 mRNA vaccines as they are formulated in lipid nanoparticles that contain a PEGylated lipid. However, there is an uncertain risk of allergy to mRNA vaccines in PEG-allergic patients and sensitivity of skin testing in the diagnosis of PEG allergy is poor. Our patient presented to Allergy and Immunology Clinic with a history of systemic reaction to PEG (in bowel prep), now requiring a mRNA booster. The patient had tolerated two doses of the AstraZeneca vaccine prior but this vaccine was no longer available in our health region due to safety concerns. Method(s): The chart was reviewed, skin prick testing to polyethylene glycol (PEG) 3350 (Restoralax diluted in water) was negative. Intradermal testing to the Pfizer-BioNTech vaccine at a dilution of 1:100 was positive at 11mm. Histamine and saline controls were appropriate. Result(s): Graded administration of the Pfizer-BioNTech vaccine was offered and consent was obtained. The patient tolerated administration of the vaccine in four divided doses (0.03cc, 0.06cc, 0.09cc, and 0.12cc). The patient was observed for 20 minutes between doses and an hour after the last dose with no reaction. Conclusion(s): We found that skin test reactivity to the Pfizer-BioNTech COVID-19 vaccine, at a nonirritating concentration (1:100), does not reliably predict reactivity on vaccine inoculation. This case highlights that it is possible to safely administer COVID-19 mRNA vaccines to patients with positive intradermal testing to the vaccine and a high suspicion for PEG allergy.
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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.
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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
Background: Until January 2022, 8.975.458 cases of COVID-19 have been reported in Spain. In December of 2020, the European Union authorized the first mRNA vaccines against SARS-COV- 2, developed by Pfizer-BioNTech and Moderna, with two doses separated by 21 and 28 days, respectively. Reports of severe allergic reactions, including anaphylaxis, have prompted concern that the new mRNA vaccine platform has the potential to cause allergic reactions (including anaphylaxis) at a greater rate than other vaccines. Method(s): Immunization process started at Hospital Ramon y Cajal (Madrid, Spain) in January 2021. The hospital provided a form to report any adverse effect after the first or second dose of the vaccine. Until today, in our Allergy Department, we have received more than 500 patients with suspected adverse reaction to the vaccine, although the data in this publication are collected from January 2021 to September 2021. All of them were referred from different services (Occupational Risk Prevention Department, Preventive Medicine Department, General Practitioners and other specialties) by telephone, e-mail or personally at our service. Result(s): Out of the 139 vaccinated patients who reported adverse effects, 131 had a reaction with the first dose, of whom 65% were women. 51% were local reactions and 49% systemic, of which 62% were immediate reactions. We performed diagnostic tests in 55% of the patients: prick test (with macrogol, triamcinolone, dexketoprofen, methylprednisolone acetate, PEG), ID test (with triamcinolone, dexketoprofen, methylprednisolone acetate) with immediate reading and delayed reading in case of delayed reactions, epicutaneous tests (with PEG and polysorbate 80) and blood tests in systemic reactions. All diagnostic tests showed negative results. 82% of patients that reported adverse effects after the first dose tolerated the second dose of the vaccine without incidents. Only one patient had a reaction to the first and second dose despite a negative study, a 58-year- old woman who presented an urticarial rash 24 hours after administration. 8 patients, all of them women, were referred for reaction after the second dose, 87% of whom had tolerated the first dose. Conclusion(s): This single-center experience suggests that most patients who had mild reactions to the first dose of mRNA vaccines have received the second dose uneventfully or with only mild repeat reactions.
ABSTRACT
Introduction (contexte de la recherche): IgE-mediated reactions to systemic corticosteroids (CSs) are rare. Hydrocortisone and methylprednisolone succinate ester are the most frequent elicitors. Excipients of depot corticosteroids (like carmellose or macrogol) may also be involved. The involvement of the dipropionate form of betamethasone (present in the depot Diprostene) has not been studied. Objectif: To describe the case of a 40-year-old woman, who presented an anaphylactic shock reaction upon intra-articular administration of Diprostene (Betamethasone sodium phosphate and betamethasone dipropionate), associated with an iodinated radiocontrast media (ICM, Xenetix). Methodes: An allergy work-up was performed, according to recommendations for severe immediate reactions. Nine months after the reaction [hypotension (7/5 mmHg), erythema and desaturation at 94%, treated with adrenalin, methylprednisolone hemisuccinate, dexchlorpheniramine] the patient underwent skin prick tests (SPT) and intradermal tests (IDT) with ICM, bethamethasone and Diprostene (commercial molecules). Latex and chlorexidine were also studied. Resultats: The tests resulted negative for ICM, latex and chlorexidine (including serum specific IgE ImmunoCAP ThermoFisher Scientific), bethametasone phosphate (IDT 0.4 mg/mL) and carmellose (IDT 0.5 mg/mL). SPT elicited a positive reaction towards Diprostene in immediate reading, (for 5, 0.5, 0.05 mg/mL) with an erythema (10, 8, 5 mm respectively) and a wheal (of at least 3 mm for each SPT). We performed an oral drug challenge to bethametasone phosphate for a total of 8 mg and it was well tolerated. The basal tryptase was 5.5 microg/mL. Tryptasemia 30 minutes after the reaction was 26.8 microg/mL. Conclusion(s): We describe an anaphylactic reaction to Diprostene, proven by positive ST. The hypothesis of allergy to betamethasone dipropionate is under investigation. The hypothesis of allergy to macrogol, the other excipient of (which was not tested separately) is less likely, since the patient received Commirnaty SARS-CoV-2 vaccine 3 months after the reaction. The allergy work-up is ongoing (tests are programmed for betamethasone dipropionate alone).Copyright © 2023
ABSTRACT
Background: The French vaccination campaign against COVID-19 was accompanied by an overwhelming increase in allergists work load highlighting our key role in the stratification of the allergy risk prior to vaccination. Method(s): In order to describe our triage and testing experience for the COVID-19 vaccination all requests were analysed in a standardized way prospectively. Our final goal was to filter the requests and avoid any delay in the vaccination process. We first set up and validated locally a questionnaire (completed by the requesting practitioner) allowing to evaluate the risk of allergy to the vaccine, based on the clinical history of the patient. Questionnaire-based allergy advices were delivered (regular vaccination or allergy testing prior to vaccination). Result(s): From January 2021 to January 2022, we addressed 1047 requests. Forty-one patients (4%) were tested. 96% had allergies to other compounds, not increasing the risk of reacting to the covid vaccines and were vaccinated safely. Half of the tested patients experienced an immediate reaction to the vaccine and the other half had a history of allergy to the vaccine's components. We identified 3 groups of patients: -Suspicions of polyethylene glycol (PEG) containing laxative allergy comprised 8 patients (26%), including 2 cases with proven IgE-mediated allergy to PEG. They were 63% (5) women, 63% (5) atopic (average age of 49 +/-10 yrs). Two thirds (63%, 5 patients) had an immediate reaction to PEG, including 3 and 2 patients with anaphylaxis with and without shock, respectively. The two allergic patients refused vaccination and received a certificate of contraindication to PEG-containing vaccines (as per French law). -Reactions to the covid vaccine comprised 21 patients: most were women (86%, 18 patients) and 29% (6) were atopic (average age was 51 +/-19 yrs). Three quarters (76%, 16 patients) presented a reaction within 1 hour after the vaccination, considered as potential anaphylaxis in 12 patients (8 patients with and 5 without shock). 100% (21 patients) were tested negative. Twenty patients (95%) were further vaccinated without reaction. One required H1 antihistamine. -Suspicions of allergy to PEG or polysorbate as excipients included 12 patients (29%). Most clinical histories were anaphylactic (42% without and 33% with shock). Following negative excipient skin testing, regular vaccination was authorized. Conclusion(s): Overall, only 4% of the initial requests were deemed eligible for allergy testing. We did not diagnose any allergy in patients who reacted to the vaccines and we delivered two certificates of contraindication to mRNA COVID-19 PEG-containing vaccines in two cases of confirmed IgE-mediated allergy to PEG.
ABSTRACT
Background: Use of ultrasound contrast agent spread increasingly in worldwide. Although few side effects are published, number of increase anaphylactic reaction is reported. A recent cautionary remark was published about polyethylene glycol (PEG) as culprit for some ultrasound contrast agent hypersensitivity (Krantz et al. JACIP. Avril 2020). A 22 years-old woman was referred for a severe anaphylaxis after a second injection of Sulphur Hexafluoride (SonoVue, Bracco, Milan, Italy). The investigation was performed to explore hepatic multinods. She already had presented with uncomfortable feeling, generalized pruritus and nausea few minutes after the first injection of Sonovue, 10 months earlier. Three months before, she has recieved also a first injection of SPIKEVAX without any reaction. As Sonovue and SPIKEVAX contain PEG, we looked for a hypersensitivity to PEG and RNAm COVID-19 vaccine. Method(s): Skin tests and basophil activation test (BAT) with expression of CD63 were performed for SonoVue, PEG 3350 and 4000 and COMIRNATY. Result(s): Skin tests were negative for all products except the undiluted IDT to COMIRNATY. BAT to PEG and SonoVue were negative but positive to COMIRNATY. Despite a fractioned administration of COMIRNATY, the patient presented with an acute urticaria few minutes after the last injection Conclusion(s): The relationship between PEG, RNAm vaccine, and hypersensitivity to SonoVue is once again highlighted by this new report. (Soni et al. J Am Soc Echocardiogr, Oct 2021).