113 - POLYCLONAL Vβ21.3 EXPANSION IN POST-VACCINATION MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN

BACKGROUND: MIS-C is a severe SARS-CoV-2-associated condition sharing clinical features with KD, but characterized by polyclonal expansion of Vβ21.3+ T cells. The incidence of MIS-C has diminished since the rise in SARS-CoV-2 infection, COVID-19 vaccination status, and the currently ruling SARS-CoV-2 variant Omicron. We report four patients diagnosed with MIS-C after recent COVID-19 immunization and aimed to assess if post-vaccination MIS-C (MIS-V) cases share the same TCR Vβ21.3 skewing seen in non-vaccinated MIS-C cases.

METHODS: We retrospectively reviewed four MIS-V patients hospitalized between December 2021 and April 2022. Prior to their MIS-V episode, all patients received mRNA vaccines (BNT162b2) based on mRNA encoding the spike protein of the original Wuhan strain. Plasma concentrations of various proteins (e.g., ST2, angiopoietin-2, lipocalin, MPO, CXCL10, IL-18, IFN-γ, IL-10, IL-6, TNF-α, CCL2, IL-1RA, sCD25) were measured by Luminex and/or automated ELISA. Immunophenotyping of the T cell repertoire, including expansion of TCR Vβ subsets, was performed by flow cytometry.

RESULTS: Within a time window of 4-5 months, four MIS-V patients after vaccination (100% male, 12.2-17.2 years old) and one healthy donor (female, 19 years old) were included (Figure 1). All patients had antibodies against the nucleocapsid as well as the spike protein, proving natural SARS-CoV-2 infection prior to MIS-V. Three patients were admitted to the ICU (patient 1, 2 and 3), two of which required inotropic support due to circulatory insufficiency (patient 2 and 3). Preliminary data indicated increased values of inflammatory proteins in the MIS-V patients, comparable to MIS-C. All patients presented with Vβ21.3+ T cell expansion and various other Vβ subsets to a lesser extent (Figure 2). Notably, in the two patients with earliest sampling post-onset of MIS-V ( < 8 days; patient 3 and 4), the frequency of Vb21.3+ T cells exceeded the reference mean value +10*standard deviation in healthy donors previously measured. Vβ21.3+ T cells displayed increased expression of T cell activation (HLA-DR, CD38) and exhaustion (PD-1, TIM-3) markers compared to Vb21.3- T cells in patients 1, 3, and 4 (Figure 3).

CONCLUSION: MIS-V patients present with clinical and biological features consistent with unvaccinated MIS-C patients, including the hallmark Vβ21.3+ T cell expansion. All patients had proven natural SARS-CoV-2 infection prior to MIS-V. Although the clinical phenotype may have been mitigated, prior immunization in these children may not have protected against the new wave of Omicron infection early 2022, and interacted with the natural SARS-CoV-2 infection, eliciting MIS-V.