Features of chronic urticaria after COVID-19 mRNA vaccine, a real-life cohort study (preprint)

Background New onsets of chronic urticaria (CU) have been reported after repeated immunizations, mainly with the Moderna mRNA-1273 vaccine (Spikevax)  Objective This study aims to evaluate patients with CU after COVID-19 mRNA vaccination. The contribution of SARS-Cov2 infection, atopy and IgE against the vaccine was analyzed. Methods We monitored the features of patients who developed CU after vaccination in the Canton of Vaud through two surveys conducted in 2022 and 2023. Fifty individuals with CU underwent blood tests, and their results were compared with individuals without a history of urticaria (N=135). The presence of anti-vaccine IgE was detected with basophil activation tests (BAT). We assessed anti-SARS-Cov2 humoral response, and the presence of IgEs against common respiratory allergens (Phadiatop) as a surrogate for atopy.  Results Post-vaccination CU occurred after a median interval of 10 days and significantly more after the Spikevax booster, affecting middle-aged individuals (median 41, 66% females). In 2023, CU was still active in 53% of the cases. Inducible forms of CU, primarily dermographism, were reported in 54% (2022) and 61% (2023) of the cases. BAT positivity was not specific to CU, anti-nucleocapsid positivity, or atopy but was significantly associated with higher anti-spike neutralizing activities and younger age. Four CU patients tolerated an additional dose of mRNA vaccine with no disease exacerbation/recurrence.  Conclusion The Spikevax booster induced anti-vaccine IgE independently of CU, the latter being not directly associated with COVID-19 infection nor atopy. The tolerance to a new booster in 4/4 patients suggests that the Spikevax vaccine indirectly triggered CU in predisposed individuals.

Omicron-specific cytotoxic T-cell responses are boosted following a third dose of mRNA COVID-19 vaccine in anti-CD20-treated multiple sclerosis patients (preprint)

Importance: The SARS-CoV-2 variant Omicron escapes neutralizing antibody responses elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third dose of vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. Objective: To determine T-cell responses to the Spike (S)-protein of Omicron in anti-CD20 treated patients before and after their third mRNA COVID-19 vaccination Design: Prospective observational monocentric study Setting: Conducted since March 2021 at the University Hospital Geneva Participants: Twenty adults with multiple sclerosis on anti-CD20 treatment (ocrelizumab) who received their third dose of mRNA COVID-19 vaccine 6 to 7 months after their second vaccination. Intervention: Blood sampling before and one month after the third vaccine dose Main outcomes and measures: Quantification of CD4 and CD8 (cytotoxic) T cells specific for SARS-CoV-2 S-protein of vaccine strain, Delta and Omicron variants , using activation marker induced assay (AIM) and comparing frequencies before and after the third vaccine dose. Results: S-specific CD4 and CD8 T-cell memory against all variants was maintained in around half of the patients six months after their second vaccination, albeit at lower frequencies against Delta and Omicron variants. A third dose enhanced the number of responders to all variants and significantly increased CD8 T-cell responses. The frequencies of T cells specific to Omicron and Delta remained lower than those specific to the vaccine strain after the boost. Conclusion and relevance: Vaccinated MS patients on anti-CD20 treatment show robust T-cell responses that recognize S from the circulating Delta and Omicron variants. Response rates increased after the third dose, demonstrating that a booster dose might improve cytotoxic T-cell mediated protection against severe disease in patients with low humoral response. The clinical relevance of the reduced frequencies of T cells specific to Omicron will need to be monitored in the future.

Patients treated with anti-CD20 therapy can mount robust T cell responses to mRNA-based COVID-19 vaccines (preprint)

ABSTRACT Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 + T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4 + and CD8 + T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.