{
  "abstract": "Multisystem inflammatory syndrome in children (MIS-C) is a severe SARS-CoV-2-associated condition that shares clinical features with Kawasaki disease (KD), characterised by a distinct polyclonal expansion of Vβ21.3+ T cells. We report five patients diagnosed with breakthrough MIS-C despite COVID-19 immunisation, all within a limited time period at the beginning of the Omicron wave, to assess whether breakthrough MIS-C cases share the same TCR Vβ21.3 skewing seen in non-vaccinated MIS-C cases. We retrospectively reviewed five MIS-C patients hospitalised between December 2021 and April 2022 despite previous immunisation against SARS-CoV-2 (BNT162b2, an mRNA vaccine against S-protein). Immunophenotyping, including TCR Vβ subset distribution, was performed in four patients.Patients (100% male, 12.2–17.2 years) had a natural breakthrough SARS-CoV-2 infection following prior immunisation (between August 2021 and February 2022). Recent infection was proven by positive SARS-CoV-2 PCR and/or IgG antibodies against the nucleocapsid protein. Blood samples of four patients were available. All presented with Vβ21.3+ T cell expansion, similar to MIS-C patients and in contrast to vaccinated historical KD patients (n=10). The two patients with the earliest sampling post-illness displayed frequencies of Vβ21.3+ T cells exceeding the reference mean value+10×SD. These Vβ21.3+ T cells showed increased surface expression of activation (HLA-DR, CD38) and exhaustion (PD-1, TIM-3) markers.In conclusion, breakthrough MIS-C patients presented with features consistent with unvaccinated MIS-C patients, including the hallmark Vβ21.3+ T cell expansion, indicating that prior immunisation with an mRNA vaccine targeting the Wuhan strain did not fully protect against MIS-C at the wave of a novel emerging variant early 2022. Trial registration number: NL41023.018.12.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands",
        "Department of Experimental Immunology, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Stejara Netea"
    },
    {
      "affiliations": [
        "CIRI, Centre International de Recherche en Infectiologie, Lyon, France"
      ],
      "name": "Liliane Khoryati"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands",
        "Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands"
      ],
      "name": "Sietse Nagelkerke"
    },
    {
      "affiliations": [
        "CIRI, Centre International de Recherche en Infectiologie, Lyon, France"
      ],
      "name": "Sarah Benezech"
    },
    {
      "affiliations": [
        "Immunopathology, Sanquin Research, Amsterdam, The Netherlands"
      ],
      "name": "Jim Keijser"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Mariken Gruppen"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Giske Biesbroek"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Beatrix Hospital, Gorinchem, The Netherlands"
      ],
      "name": "Roel Lubbers"
    },
    {
      "affiliations": [
        "Department of Neonatal and Pediatric Intensive Care, Erasmus MC Sophia, Rotterdam, The Netherlands"
      ],
      "name": "Naomi Ketharanathan"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Emilie Buddingh"
    },
    {
      "affiliations": [
        "Pediatric Intensive Care Unit, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Nikki Schoenmaker"
    },
    {
      "affiliations": [
        "Department of HLA Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands"
      ],
      "name": "Arianne Brandsma"
    },
    {
      "affiliations": [
        "Immunopathology, Sanquin Research, Amsterdam, The Netherlands",
        "Amsterdam Institute for Infection & Immunity, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Theo Rispens"
    },
    {
      "affiliations": [
        "Pediatric Cardiology, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Irene Kuipers"
    },
    {
      "affiliations": [
        "CIRI, Centre International de Recherche en Infectiologie, Lyon, France",
        "Pediatric Rheumatology Department, National Reference Centre for Rare Rheumatism, autoimmune diseases and interferonopathies (RAISE), National Reference Centre for Rare Autoinflammatory Diseases and Amyloidosis (CEREMAIA), ERN RITA, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Alexandre Belot"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands",
        "Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands"
      ],
      "name": "Taco Kuijpers"
    }
  ],
  "title": "Polyclonal Vβ21.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination",
  "uid": "50351911-ac4d-55ba-a354-61ec751680e0"
}