The rapid development and deployment of COVID-19 vaccines marked a pivotal moment in the global response to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Among the most widely used vaccines were the mRNA-1273 (Spikevax®) from Moderna and BNT 162b2 (Comirnaty®) from Pfizer-BioNTech, authorized in January 2021 and December 2020, respectively. These vaccines played a significant role in mitigating the pandemic’s impact, yet they were also associated with a range of adverse effects, including chronic urticaria (CU).
Chronic urticaria, characterized by wheals (hives) and angioedema lasting more than six weeks, emerged as a concern following COVID-19 vaccination campaigns. This article delves into the specific context of Switzerland, where an outbreak of CU was observed starting in December 2021. Pharmacovigilance data from Swissmedic revealed up to 17,000 reports of suspected adverse drug reactions by February 2023, highlighting the need for detailed analysis and understanding of these effects.
Analyzing the incidence rates and risk factors associated with CU post-COVID-19 vaccination is crucial. A study conducted in Switzerland estimated the crude incidence rate of CU after a COVID-19 booster, with a significantly higher relative risk associated with the Spikevax vaccine compared to Comirnaty. Immunological data from patients revealed systematic sensitization against mRNA lipid nanoparticles, raising questions about the pathogenesis and persistence of CU following vaccination.
Moreover, the impact of variants such as omicron on CU development adds complexity to the analysis. To deepen our understanding, this article presents findings from surveys conducted in the Canton of Vaud, comparing patients with CU to those infected with SARS-CoV-2 or vaccinated with mRNA vaccines. Insights from blood tests and patient characteristics shed light on the features and potential mechanisms underlying CU post-vaccination, contributing to ongoing discussions and strategies for vaccine safety and monitoring.
DISCUSSION : Comprehensive Analysis of Chronic Urticaria Post-mRNA Vaccination
This study delves into a broad analysis of a significant number of patients who developed chronic urticaria (CU) after receiving mRNA-based vaccinations, predominantly Moderna’s. Similar observations have been noted by other researchers. The patient demographic primarily comprised middle-aged individuals, with a notable 54-61% suffering from an inducible form of CU. This research aims to clarify the relationship between CU and mRNA vaccinations, exploring potential causative factors and the body’s response to subsequent vaccine doses.
Patient Demographics and Clinical Observations
The study highlighted that the majority of the CU cases occurred in middle-aged patients. Notably, a substantial fraction, between 54% and 61%, had an inducible form of CU, suggesting a possible link to external triggers. The analysis revealed no direct correlation between the Omicron variant of COVID-19, atopic predisposition, or vaccine sensitization, and the onset of CU. This finding is crucial as it helps differentiate CU from other conditions that might share similar triggers.
Response to Re-exposure to mRNA Vaccines
A pivotal aspect of the study was examining CU patients’ response to re-exposure to mRNA vaccines. All four patients in the study who were re-exposed to the mRNA vaccine did not show exacerbation of CU and tolerated the vaccine well. This observation aligns with another report involving four CU patients at a military academy who received a subsequent COVID-19 booster vaccine without any aggravation of their condition. These findings suggest that mRNA vaccines might not be a direct trigger for exacerbating CU in individuals previously diagnosed with the condition.
Sensitization to mRNA Vaccines
The research also uncovered a group of patients sensitized to mRNA vaccines, irrespective of known allergies or active CU. This aligns with the observed higher prevalence of positive skin tests in individuals vaccinated with Spikevax. The sensitization is believed to be mediated by specific IgE against the spherical polyethylene glycol (PEG) conformation in the lipid nanoparticles of the vaccines. While the clinical significance of these IgEs remains uncertain, they could play a role in protective immunity or predispose individuals to allergic reactions. This duality necessitates further investigation to fully understand the implications of vaccine-induced IgE responses.
IgE-Mediated Responses and Anaphylaxis
The study delved into the role of IgE in vaccine-related sensitivities, uncovering that immediate reactions to vaccines are predominantly non-IgE dependent, often triggered by complement activation. The presence of IgE against PEG in lipid nanoparticles is common after multiple exposures to mRNA vaccines. However, the true clinical impact of these IgE antibodies remains to be determined, necessitating ongoing research and monitoring.
Atopy and Chronic Urticaria
Investigating the link between atopy and CU, the study found no direct association. The incidence of allergic rhinitis among CU patients was similar to the general population, further supported by Phadiatop analysis results. This finding suggests that while atopy and CU may coexist, they do not have a clear pathogenetic relationship.
Impact of COVID-19 and Vaccination Trends
The research analyzed the incidence of CU in relation to the spread of the Omicron variant and vaccination patterns. Switzerland reported a higher incidence of CU, potentially linked to the extensive use of Spikevax. The study also explored the timing of CU case onset relative to booster vaccinations and COVID-19 waves, suggesting no direct link between CU onset and COVID-19 infections.
Vaccine Composition and CU Incidence
The study highlighted the difference in mRNA content between Spikevax (100 μg) and Comirnaty (30 μg), which may contribute to the higher incidence of CU following Spikevax administration. Differences in vaccine stability and the nature of lipid nanoparticle (LNP) carriers between the two vaccines were also examined as potential factors affecting CU incidence and immunogenicity.
Limitations and Future Research Directions
The study acknowledges several limitations, including potential selection biases and the lack of control groups for non-vaccine-related CU cases. The absence of certain immunological tests and assessments also highlights areas for future research, particularly in exploring autoimmune mechanisms and the broader implications of vaccine-induced sensitivities.
The study concludes that CU post-mRNA vaccination is a complex phenomenon with no direct linkage to specific triggers like the Omicron variant, atopic conditions, or vaccine sensitization. The ability of some individuals to tolerate additional vaccine doses without exacerbating CU points to a nuanced interplay between vaccination and individual predispositions. Future research should aim to unravel the specifics of the autoantibody response in CU, enhancing our understanding of its development post-vaccination and potentially refining vaccine administration strategies for at-risk populations.
REFERENCE LINK : https://www.researchsquare.com/article/rs-4113785/v1
