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


Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
07 Jun 2020
Historique:
entrez: 25 6 2020
pubmed: 25 6 2020
medline: 25 6 2020
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 32577677
doi: 10.1101/2020.06.05.20123117
pmc: PMC7302282
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : Department of Health
ID : CS-2015-15-016
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17183
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

Marisol Perez-Toledo (M)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Sian E Faustini (SE)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Sian E Jossi (SE)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Adrian M Shields (AM)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Hari Krishnan Kanthimathinathan (HK)

Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, B15 2TT, U.K.
Paediatric Intensive Care Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.

Joel D Allen (JD)

School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.

Yasunori Watanabe (Y)

School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.

Margaret Goodall (M)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

David C Wraith (DC)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Tonny V Veenith (TV)

Department of Critical Care Medicine, University Hospitals Birmingham NHS Trust, Birmingham, B15 2TH, UK.

Mark T Drayson (MT)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Deepthi Jyothish (D)

Department of General Paediatrics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.

Eslam Al-Abadi (E)

Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, B15 2TT, U.K.
Childhood Arthritis and Rheumatic Diseases Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.

Ashish Chikermane (A)

Department of Cardiology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.

Steven B Welch (SB)

Department of Paediatrics, Birmingham Chest Clinic and Heartlands Hospital, University Hospitals Birmingham, Birmingham, B9 5SS, U.K.

Kavitha Masilamani (K)

Department of General Paediatrics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.

Scott Hackett (S)

West Midlands Immunodeficiency Centre, Heartlands Hospital, University Hospitals Birmingham, Birmingham, B9 5SS, U.K.

Max Crispin (M)

School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.

Barnaby R Scholefield (BR)

Paediatric Intensive Care Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, U.K.
Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, U.K.

Adam F Cunningham (AF)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Alex G Richter (AG)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

Classifications MeSH