Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome

Research output: Contribution to journalArticle


  • Sian E Jossi
  • Hari Krishnan Kanthimathinathan
  • Joel D Allen
  • Yasunori Watanabe
  • David C Wraith
  • Tonny V Veenith
  • Deepthi Jyothish
  • Eslam Al-Abadi
  • Ashish Chikermane
  • Steven B Welch
  • Kavitha Masilamani
  • Scott Hackett
  • Max Crispin
  • Barney Scholefield
  • Adam Cunningham
  • Alex Richter

External organisations

  • Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, United Kingdom; Department of Gastroenterology, University Hospital Birmingham, Birmingham, United Kingdom. Electronic address:
  • MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Southampton Nutrition Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Departments of Cardiology, Sandwell and West Birmingham Hospitals NHS Trust and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Department of Paediatrics, Haematology and Oncology, Department of General Nursery, Medical University of Gdansk, Gdansk, Poland.
  • Childhood Arthritis and Rheumatic Diseases Unit
  • Birmingham Women's and Children's NHS Foundation Trust
  • Department of Cardiology
  • Sandwell and West Birmingham Hospitals (SWBH) and University Hospitals Birmingham (UHB) NHS Trust, Birmingham, United Kingdom.
  • Paediatric Intensive Care Unit
  • Institute for Inflammation and Ageing


Background: During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.

Methods: Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.

Results: Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.

Conclusions: Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.


Original languageEnglish
JournalmedRxiv : the preprint server for health sciences
Publication statusPublished - 7 Jun 2020