Allergic reactions to the Ad26.COV2.S Vaccine in South Africa (preprint)

Abstract ( n=254/250 words)   Background: The Janssen-Ad26.COV2.S vaccine is authorised for use in several countries with more than 30 million doses administered. Mild and severe allergic adverse events following immunisation(AEFI) have been reported. The aim of this report is to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. Methods: : A single-dose of the Ad26.COV2.S vaccine was administered to 477234 South African Healthcare Workers between 17 February and 17 May 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy”. Anaphylaxis adjudication was performed using the Brighton Collaboration (BCC) and NIAID case definitions.  Results: : A large cohort of South African healthcare workers received the Ad26.COV2.S vaccination. Only 250(0.052%) patients reported any allergic-type reaction(less than 1 in 2000), with four cases of adjudicated anaphylaxis (BCC level 1, n=3)(prevalence of 8.4 per million doses). All anaphylaxis cases had a prior history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest non-anaphylatic reactions and included: self-limiting, transient/localised rashes requiring no healthcare contact(n=91); or isolated urticaria and/or angioedema[n=70 median  onset 48(IQR 11.5-120) hours post vaccination] that necessitated healthcare contact(81%), antihistamine(63%), and/or systemic/topical corticosteroid(16%). All immediate (including adjudicated anaphylaxis) and the majority of delayed AEFI(65/69) cases resolved completely.   Conclusions: : Allergic AEFI are rare following a single-dose of Ad26.COV with complete resolution in  all cases of anaphylaxis. Though rare, isolated, delayed onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.   Keywords: allergic reaction, anaphylaxis, COVID19 adenovirus vaccine; Janssen-Ad26.COV2.S vaccine, urticaria

Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: a Clinical Observation of Four patients. (preprint)

Background Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), which leads to recurrent episodes of bradykininmediated edema. Lanadelumab is a plasma kallikrein inhibitor that is the only first line therapy for long term prophylaxis (LTP) of HAE attacks in China since 2021.Objectives To observe the clincial efficacy and safety of lanadelumab in Chinese patients with HAE in a small population of four patients.Method Four HAE patients from three academic centers in China was included. Demographic characteristics, clinical manifestions and life quality of HAE patients were recorded before and after LTP treatment of lanadelumab .The primary outcome is the attack frequence of symptoms, and disease-related work loss days. The secondary outcome is the improved life quality of patients. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL).Results Lanadelumab led to the reductions of 98.04% and 100% in attack rate and treated attack rate respectively. Three patients of four (75%) reported complete remission from attacks after starting the administration of lanadelumab. Two patients had significant improvements on AE-QoL and DLQI (both scores reduction rate were 100%) in early period of treatment (4 weeks and 2 weeks, respectively) and all the patients had significant improvement on missed work days/year (reduction rate was 100%). The efficacy of lanadelumab was stable during vaccination and infection with COVID-19. No treatment-related serious/severe treatment emergent adverse events (TEAEs) occured during the treatment of lanadelumab.Conclusions Our study first demonstrated the clinical efficacy of lanadelumab with highly safety in Chinese HAE patients. A reasonable dosage plan can ensure the stability of therapeutic effects of lanadelumab. Moreover, lanadelumab also play a protective role to prevent attack in the case of COVID-19 infection.

[Reasons for allergology consultations prior to COVID-19 vaccination and their outcomes : Two-year experience of an allergy center in North Rhine-Westphalia]. / Gründe für allergologische Diagnostik und deren Ergebnisse im Kontext von COVID-19-Vakzinierungen : 2-jährige Erfahrung eines Allergiezentrums in Nordrhein-Westfalen.

BACKGROUND: To counteract the coronavirus disease 2019 (COVID-19) pandemic, several severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines have been licensed since December 2020. Shortly after the start of the vaccination campaigns, occasional allergic reactions related to vaccines were described, thus, leading to concerns in many patients with a history of allergies. The aim of this work was to evaluate which anamnestic events represented a reason for an allergology work-up before COVID-19 vaccination. Furthermore, the results of the allergology diagnostics are described. METHODS: We performed a retrospective data analysis of all patients who presented at the Center for Dermatology, Allergology and Dermatosurgery of the Helios University Hospital Wuppertal during the years 2021 and 2022 for allergology work-up prior to COVID-19 vaccination. Demographic data, allergological history, reason for the consultation in the clinic and results of allergology diagnostic tests including reactions after vaccination were included. RESULTS: A total of 93 patients presented for allergology work-up with COVID-19 vaccines. In about half of the cases, the reasons for the presentation to the clinic were doubts and concerns about allergic reactions and side effects. In all, 26.9% (25/93) of the presented patients had not previously received a COVID-19 vaccine yet and 23.7% (22/93) of patients developed non-allergic reactions after prior COVID-19 vaccine (e.g., headache, chills, fever, malaise). Of the patients, 46.2% (43/93) were successfully vaccinated in the clinic due to a complex allergological history, while the remaining 53.8% (50/93) were subjected to outpatient vaccination in the vaccination practice. Only one patient with known chronic spontaneous urticaria developed a mild angioedema of the lips a few hours after vaccination; however, we do not consider this episode an allergic reaction to the vaccine due to the time delay. CONCLUSION: Allergic reactions after COVID-19 vaccines are rare, but many patients with a positive medical history of allergies are concerned about allergic reactions after COVID-19 vaccination. Thus, public work by practicing allergologists is important during vaccination campaigns to meet the concerns and fears of the population, especially of patients with allergies in their medical history.

Prolonged angioedema after Pfizer-BioNTech COVID-19 vaccine.

This case reports a woman in her 40s with a history of allergic reaction to shellfish and iodine who presented with tongue angioedema, difficulty breathing and chest tightness after receiving the first dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Her angioedema remained for 10 days post-exposure to the vaccine, requiring 3 days of epinephrine infusion. She was discharged with advice to avoid further mRNA vaccines. This case highlights the increasing awareness needed of polyethylene glycol (PEG) allergy and the protracted nature of her reaction. A firm conclusion cannot be reached based on a single case report. More research is needed to understand whether there is a causal relationship between the BNT162b2 vaccine and PEG allergy. Awareness regarding PEG allergy and the complexities associated with it is important and needs to be raised due to its prevalent use in diverse industries.

Allergy to Omalizumab: Lessons from a Reaction to the Coronavirus 2019 Vaccine.

Omalizumab can cause hypersensitivity reactions. We herein report the first case of an 18-year-old woman with refractory cough-predominant asthma that correlated with allergic reactions caused by omalizumab and the coronavirus disease 2019 (COVID-19) vaccine. The patient developed angioedema after taking omalizumab. She had previously experienced intense coughing immediately after receiving a COVID-19 vaccine. A skin prick test was positive for polysorbate 20, which was probably the cause of the allergic reactions to omalizumab and the COVID-19 vaccine. Clinicians should check for an allergic reaction, irrespective of its intensity, triggered by polysorbate and be careful when prescribing biologics to patients in order to avoid allergic reactions.

A favipiravir-induced angioedema and urticaria in a COVID-19 patient.

Although favipiravir is a promising drug for coronavirus disease 2019, some adverse effects, including skin lesions, have been reported. A 56-year-old female who was prescribed favipiravir by a filiation team following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test presented to our hospital. After examination, favipiravir and paracetamol were prescribed. She represented to the hospital with facial swelling and itchy rashes on her forearm. Angioedema and urticaria were diagnosed. Favipiravir was discontinued. Steroid and antihistaminic therapy were administered for angioedema. To our knowledge, this is the first reported case of favipiravir-induced angioedema and urticaria in Turkey.

Urticaria and angioedema in children and adolescents: diagnostic challenge.

Urticaria diagnosis may be challenging in children since it can be triggered or related to numerous conditions. In this paper, we reviewed the main aspects regarding the diagnosis of urticaria in the pediatric population. Acute urticaria is often due to viral infections. However, other culprits, including foods, insect stings, drugs, contrast media, vaccination, latex, and medical diseases, may account for acute patterns. Laboratory tests and confirmatory allergy tests should be individualized and guided by history. Chronic urticaria (CU) is defined when hives and/or angioedema last for more than 6 weeks. The most common type of chronic urticaria in children is chronic spontaneous urticaria (CSU). Chronic inducible urticaria (CindU) is less common but is important to diagnose in order to manage appropriately and reduce the risk of severe reactions. Inducible forms in children are often diagnosed with specific provocation tests similar to the tests used in adults. Given that chronic urticaria could rarely be a presentation of vasculitis, systemic-onset juvenile idiopathic arthritis, or auto-inflammatory syndromes, it is important to rule out these conditions. It is crucial to differentiate cases of chronic urticaria from mastocytosis and Bradykinin-mediated angioedema, given that treatment may differ. The management of chronic urticaria in children has improved over the last decade because of the development of both clear management guidelines and new effective drugs. It is crucial to increase awareness for appropriate diagnosis and new available treatment to improve the management of chronic urticaria in children.

Eyelid edema following the first Pfizer-BioNTech COVID-19 vaccination: is it a coincidence?

OBJECTIVE: This report describes an ocular allergic reaction manifested as eyelid edema after Pfizer-BioNTech COVID-19 vaccination. CASE DESCRIPTION: A 28-year-old female had the first Pfizer-BioNTech COVID-19 vaccine dose and was discharged following a 20-minute post-vaccination observation for potential adverse complications. She came to the emergency department after her left eyelid swelled unexpectedly two hours later, accompanied by itching and redness. Aside from left eyelid edema and redness, there were no other remarkable bilateral ocular findings. The lack of recent history of any cause of eyelid edema suggested a vaccine-induced ocular allergy. Immediate administration of systemic and topical anti-allergic medications resulted in a significant clinical improvement within 4-6 hours. CONCLUSIONS: Reporting any adverse reactions to vaccines, especially recently approved ones, is extremely critical. Local ocular allergy, as opposed to systemic allergy, could be considered one of the COVID 19 vaccine's rare and mild side effects.

Cutaneous reactions after COVID-19 vaccination in Turkey: A multicenter study.

OBJECTIVES: In this study covering all of Turkey, we aimed to define cutaneous and systemic adverse reactions in our patient population after COVID-19 vaccination with the Sinovac/CoronaVac (inactivated SARS-CoV-2) and Pfizer/BioNTech (BNT162b2) vaccines. METHODS: This prospective, cross-sectional study included individuals presenting to the dermatology or emergency outpatient clinics of a total of 19 centers after having been vaccinated with the COVID-19 vaccines. Systemic, local injection site, and non-local cutaneous reactions after vaccination were identified, and their rates were determined. RESULTS: Of the 2290 individuals vaccinated between April 15 and July 15, 2021, 2097 (91.6%) received the CoronaVac vaccine and 183 (8%) BioNTech. Systemic reactions were observed at a rate of 31.0% after the first CoronaVac dose, 31.1% after the second CoronaVac dose, 46.4% after the first BioNTech dose, and 46.2% after the second BioNTech dose. Local injection site reactions were detected at a rate of 35.6% after the first CoronaVac dose, 35.7% after the second CoronaVac dose, 86.9% after the first BioNTech dose, and 94.1% after the second BioNTech dose. A total of 133 non-local cutaneous reactions were identified after the CoronaVac vaccine (2.9% after the first dose and 3.5% after the second dose), with the most common being urticaria/angioedema, pityriasis rosea, herpes zoster, and maculopapular rash. After BioNTech, 39 non-local cutaneous reactions were observed to have developed (24.8% after the first dose and 5% after the second dose), and the most common were herpes zoster, delayed large local reaction, pityriasis rosea, and urticaria/angioedema in order of frequency. Existing autoimmune diseases were triggered in 2.1% of the patients vaccinated with CoronaVac and 8.2% of those vaccinated with BioNTech. CONCLUSIONS: There are no comprehensive data on cutaneous adverse reactions specific to the CoronaVac vaccine. We determined the frequency of adverse reactions from the dermatologist's point of view after CoronaVac and BioNTech vaccination and identified a wide spectrum of non-local cutaneous reactions. Our data show that CoronaVac is associated with less harmful reactions while BioNTech may result in more serious reactions, such as herpes zoster, anaphylaxis, and triggering of autoimmunity. However, most of these reactions were self-limiting or required little therapeutic intervention.

Facial Angioedema after the first dose of Covishield (adenovirus-vectored severe acute respiratory syndrome coronavirus 2 vaccine): follow-up after the second and third booster doses.

Mass vaccination campaigns are essential to control the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic. The Covishield vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, which contains the full-length structural spike protein of SARS-CoV-2. Occasionally, it can lead to cutaneous reactions that contribute to fear of vaccination, hesitancy, and incomplete vaccination schedules. We report a case of facial angioedema following the first dose of Covishield in a 63-year-old woman with no previous history of allergies or hypersensitivity to drugs or vaccines. No rebound of angioedema was recorded after the second homologous and third heterologous doses.

Angioedema after favipiravir treatment: Two cases.

Drug-induced angioedema often affects elderly patients with chronic drug use. Proper diagnosis and prompt with effective treatment reduce mortality. With the increasing use of favipiravir, many side effects, especially increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels due to liver toxicity, and also skin lesions are reported. First patient oral favipiravir treatment on the second day was admitted to the hospital with rash and swelling on the eyelids. Second patient suffered from significant swelling on the upper lip and displayed angioedema. In this cases, angioedema findings regressed after rapid diagnosis and parenterally administered antihistamine and steroid treatment. Although there is no effective drug therapy in the treatment of COVID-19, favipiravir is also included in the treatment protocols in many countries. Clinicians should be careful about the side effects and possible skin manifestations, especially including angioedema, related to the use of favipiravir.

COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.

Background: Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data have been available to explore this hypothesis. Objective: To assess the interrelationship(s) between COVID-19 and HAE. Methods: Self-reported COVID-19 infection, complications, morbidity, and mortality were surveyed by using an online questionnaire. The participants included subjects with HAE with C1 inhibitor (C1INH) deficiency (HAE-C1INH) and subjects with HAE with normal C1-inhibitor (HAE-nl-C1INH), and household controls (normal controls). The impact of HAE medications was examined. Results: A total of 1162 participants who completed the survey were analyzed, including: 695 subjects with HAE-C1INH, 175 subjects with HAE-nl-C1INH, and 292 normal controls. The incidence of reported COVID-19 was not significantly different between the normal controls (9%) and the subjects with HAE-C1INH (11%) but was greater in the subjects with HAE-nl-C1INH (19%; p = 0.006). Obesity was positively correlated with COVID-19 across the overall population (p = 0.012), with a similar but nonsignificant trend in the subjects with HAE-C1INH. Comorbid autoimmune disease was a risk factor for COVID-19 in the subjects with HAE-C1INH (p = 0.047). COVID-19 severity and complications were similar in all the groups. Reported COVID-19 was reduced in the subjects with HAE-C1INH who received prophylactic subcutaneous C1INH (5.6%; p = 0.0371) or on-demand icatibant (7.8%; p = 0.0016). The subjects with HAE-C1INH and not on any HAE medications had an increased risk of COVID-19 compared with the normal controls (24.5%; p = 0.006). Conclusion: The subjects with HAE-C1INH who were not taking HAE medications had a significantly higher rate of reported COVID-19 infection. Subcutaneous C1INH and icatibant use were associated with a significantly reduced rate of reported COVID-19. The results implicated potential roles for the complement cascade and tissue kallikrein-kinin pathways in the pathogenesis of COVID-19 in patients with HAE-C1INH.

May macroglossia in COVID-19 be related not only to angioedema?

SARS-CoV-2 infection can lead to a variety of clinical manifestations. The occurrence of tongue swelling has recently reported in severe cases of COVID-19, and angioedema has suggested as the causative mechanism. Several factors, such as genetic predisposing factor and angiotensin-converting enzyme inhibitors (ACEI) therapies, have proposed to induce angioedema, especially as concerns patients requiring ICU treatments. Nevertheless, the question is still debated and other causes not yet recognized should be considered. Here we present a case of macroglossia occurred in a patient deceased for COVID-19 disease, who had no family history of angioedema and did not receive ACEI as antihypertensive drug. Histological and immune-histochemical analysis revealed tongue muscle atrophy with infiltrating macrophages suggesting repair mechanisms, as seen in nerve injury recovery. These new pathological findings may open new fields of study on the pathogenesis of SARS-CoV-2.