Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage

Tala El Tal^#¹, Marie-Paule Morin^#², Shaun K Morris^#^{3

4

5

6}, Daniel S Farrar⁷, Roberta A Berard⁸, Fatima Kakkar⁹, Charlotte Moore Hepburn¹⁰, Krista Baerg^{11

12}, Camille Beaufils², Terri-Lyn Bennett¹³, Susanne M Benseler^{14

15}, Guillaume Beaudoin-Bussières^{16

17}, Kevin Chan^{18

19}, Claude Cyr²⁰, Nagib Dahdah²¹, Elizabeth J Donner²², Olivier Drouin^{23

24}, Rojiemiahd Edjoc¹³, Maryem Eljaouhari¹³, Joanne E Embree^{25

26}, Catherine Farrell²⁷, Andrés Finzi^{16

17}, Sarah Forgie²⁸, Ryan Giroux²⁹, Kristopher T Kang³⁰, Melanie King³¹, Melanie Laffin Thibodeau³¹, Bianca Lang³², Ronald M Laxer¹, Thuy Mai Luu²³, Brian W McCrindle³³, Julia Orkin^{10

34}, Jesse Papenburg^{35

36}, Catherine M Pound³⁷, Victoria E Price³⁸, Jean-Philippe Proulx-Gauthier³⁹, Rupeena Purewal^{11

40}, Manish Sadarangani^{30

41}, Marina I Salvadori¹³, Roseline Thibeault⁴², Karina A Top⁴³, Isabelle Viel-Thériault⁴⁴, Elie Haddad⁴⁵, Rosie Scuccimarri⁴⁶, Rae S M Yeung^{47

48

49}

Affiliations

¹ Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
² Division of Paediatric Rheumatology-Immunology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
³ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁴ Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁵ Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁶ Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁷ Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada.
⁸ Division of Rheumatology, Department of Pediatrics, London Health Sciences Centre, London, ON, Canada.
⁹ Division of Infectious Diseases, CHU Sainte-Justine, Montreal, QC, Canada.
¹⁰ Department of Pediatrics, Division of Paediatric Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada.
¹² Division of General Pediatrics, Jim Pattison Children's Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
¹³ Public Health Agency of Canada, Ottawa, ON, Canada.
¹⁴ Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁵ Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
¹⁶ Department of Microbiology, Immunology and Infectious Diseases, Université de Montréal, Montreal, QC, Canada.
¹⁷ Centre de Recherche du CHUM, Montreal, QC, Canada.
¹⁸ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Children's and Women's Health, Trillium Health Partners, Mississauga, ON, Canada.
²⁰ Service de Soins Intensifs Pédiatriques, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
²¹ Division of Pediatric Cardiology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
²² Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
²³ Division of General Pediatrics, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.
²⁴ Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, QC, Canada.
²⁵ Department of Paediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
²⁶ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
²⁷ Division of Paediatric Intensive Care, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.
²⁸ Division of Infectious Diseases, Department of Pediatrics, University of Alberta and Stollery Children's Hospital, Edmonton, AB, Canada.
²⁹ Women's and Children's Health Program, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³⁰ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
³¹ Canadian Paediatric Surveillance Program, Canadian Paediatric Society, Ottawa, ON, Canada.
³² Division of Rheumatology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
³³ The Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
³⁴ Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
³⁵ Division of Pediatric Infectious Diseases, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada.
³⁶ Division of Microbiology, Department of Clinical Laboratory Medicine, McGill University Health Centre, Montreal, QC, Canada.
³⁷ Division of Consulting Pediatrics, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
³⁸ Division of Paediatric Hematology/Oncology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
³⁹ Department of Pediatrics, CHU de Québec-Université Laval, Quebec City, QC, Canada.
⁴⁰ Division of Paediatric Infectious Diseases, Jim Pattison Children's Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
⁴¹ Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
⁴² Division of Pediatric Infectious Diseases, Department of Paediatrics, CHU de Quebec-University of Laval, Quebec City, QC, Canada.
⁴³ Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁴⁴ Division of Infectious Diseases, Department of Pediatrics, CHU de Québec-Université Laval, Quebec City, QC, Canada.
⁴⁵ Division of Paediatric Rheumatology-Immunology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada. elie.haddad@umontreal.ca.
⁴⁶ Division of Paediatric Rheumatology, Montreal Children's Hospital/McGill University Health Centre, Montreal, QC, Canada.
⁴⁷ Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. rae.yeung@sickkids.ca.
⁴⁸ Cell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada. rae.yeung@sickkids.ca.
⁴⁹ Department of Immunology and Institute of Medical Science, University of Toronto, Toronto, ON, Canada. rae.yeung@sickkids.ca.

^# Contributed equally.

PMID: 37277605
PMCID: PMC10241135
DOI: 10.1038/s41390-023-02668-1

Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage

Tala El Tal et al. Pediatr Res. 2023 Nov.

. 2023 Nov;94(5):1744-1753.

doi: 10.1038/s41390-023-02668-1. Epub 2023 Jun 5.

Authors

Affiliations

¹ Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
² Division of Paediatric Rheumatology-Immunology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
³ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁴ Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁵ Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁶ Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. shaun.morris@sickkids.ca.
⁷ Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada.
⁸ Division of Rheumatology, Department of Pediatrics, London Health Sciences Centre, London, ON, Canada.
⁹ Division of Infectious Diseases, CHU Sainte-Justine, Montreal, QC, Canada.
¹⁰ Department of Pediatrics, Division of Paediatric Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada.
¹² Division of General Pediatrics, Jim Pattison Children's Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
¹³ Public Health Agency of Canada, Ottawa, ON, Canada.
¹⁴ Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁵ Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
¹⁶ Department of Microbiology, Immunology and Infectious Diseases, Université de Montréal, Montreal, QC, Canada.
¹⁷ Centre de Recherche du CHUM, Montreal, QC, Canada.
¹⁸ Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Children's and Women's Health, Trillium Health Partners, Mississauga, ON, Canada.
²⁰ Service de Soins Intensifs Pédiatriques, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
²¹ Division of Pediatric Cardiology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
²² Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
²³ Division of General Pediatrics, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.
²⁴ Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, QC, Canada.
²⁵ Department of Paediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
²⁶ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
²⁷ Division of Paediatric Intensive Care, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.
²⁸ Division of Infectious Diseases, Department of Pediatrics, University of Alberta and Stollery Children's Hospital, Edmonton, AB, Canada.
²⁹ Women's and Children's Health Program, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³⁰ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
³¹ Canadian Paediatric Surveillance Program, Canadian Paediatric Society, Ottawa, ON, Canada.
³² Division of Rheumatology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
³³ The Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
³⁴ Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
³⁵ Division of Pediatric Infectious Diseases, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada.
³⁶ Division of Microbiology, Department of Clinical Laboratory Medicine, McGill University Health Centre, Montreal, QC, Canada.
³⁷ Division of Consulting Pediatrics, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
³⁸ Division of Paediatric Hematology/Oncology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
³⁹ Department of Pediatrics, CHU de Québec-Université Laval, Quebec City, QC, Canada.
⁴⁰ Division of Paediatric Infectious Diseases, Jim Pattison Children's Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
⁴¹ Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
⁴² Division of Pediatric Infectious Diseases, Department of Paediatrics, CHU de Quebec-University of Laval, Quebec City, QC, Canada.
⁴³ Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁴⁴ Division of Infectious Diseases, Department of Pediatrics, CHU de Québec-Université Laval, Quebec City, QC, Canada.
⁴⁵ Division of Paediatric Rheumatology-Immunology, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada. elie.haddad@umontreal.ca.
⁴⁶ Division of Paediatric Rheumatology, Montreal Children's Hospital/McGill University Health Centre, Montreal, QC, Canada.
⁴⁷ Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. rae.yeung@sickkids.ca.
⁴⁸ Cell Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada. rae.yeung@sickkids.ca.
⁴⁹ Department of Immunology and Institute of Medical Science, University of Toronto, Toronto, ON, Canada. rae.yeung@sickkids.ca.

^# Contributed equally.

PMID: 37277605
PMCID: PMC10241135
DOI: 10.1038/s41390-023-02668-1

Abstract

Background: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU).

Methods: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression.

Results: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU.

Conclusions: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages.

Impact: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

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Conflict of interest statement

M.-P.M. has received consulting fees from Sobin and AbbVie and payment for expert testimony from the Canadian Medical Protective Association. S.K.M. has received honoraria for lectures from GlaxoSmithKline, was a member of ad hoc advisory boards for Pfizer Canada and Sanofi Pasteur, and is an investigator on an investigator-led grant from Pfizer. R.A.B. has received honoraria and participated in advisory boards with SOBI, Roche, Amgen, and AbbVie. K.B. served as Past President of the Community Paediatrics Section of the Canadian Paediatric Society and has received royalties from Brush Education. K.C. is Chair of the Acute Care Committee of the Canadian Paediatric Society and is past president of the Emergency Medicine Section of the Canadian Paediatric Society. E.J.D. is Chair of the Scientific Research Committee and a director of Epilepsy Canada. She is also a member of Partners Against Mortality in Epilepsy and the advisory boards of Cardiol, Pendopharm and Stoke Therapeutics. C.F. is Chair of the Scientific Steering Committee for the Canadian Paediatric Surveillance Program, former Chair of the Specialty Committee in Pediatrics of the Royal College of Physicians and Surgeons of Canada, former President of the Canadian Paediatric Society, and member of the Executive as Secretary of the Canadian Critical Care Society. She has received reimbursement for travel expenses from Canadian Paediatric Society and the Royal College of Physicians and Surgeons of Canada. She has also received an honorarium for a presentation at a continuing education conference from the Université de Sherbrooke. S.F. is the President of the Association of Medical Microbiology and Infectious Disease Canada and has received consulting fees from Toronto Metropolitan University. F.K. has received honoraria for presentations given to the Association des Pédiatres du Québec and receives CMV testing kits from Altona Diagnostics. R.M.L. has received honoraria for serving as a consultant to Sobi, Novartis, Sanofi, and Eli Lilly, as chair for data monitoring committees for Eli Lilly and Novartis, and from the Canadian Rheumatology Association. C.M.H. is the Director of Children’s Mental Health of Ontario, and the Director of medical affairs for the Canadian Paediatric Society and the Canadian Paediatric Surveillance Program. J.P. reports grants from MedImmune, grants and personal fees from Merck and AbbVie, and personal fees from AstraZeneca, all outside the submitted work. R.P. is a consultant for Verity Pharmaceuticals. M.S. is supported via salary awards from the BC Children’s Hospital Foundation and the Michael Smith Foundation for Health Researc and has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. M.L.S. is an employee of the Public Health Agency of Canada. R.S. has received honoraria and served on an advisory board and as a consultant with Novartis, honoraria from Canadian Rheumatology Association, is a board member for Rheumatology for All, and her institution receives funding from Bristol Myers Squibb for a patient registry for which she is PO. E.H. has participated in advisory board meetings of CSL-Behring and Takeda, data safety monitoring boards of Rocket Pharmaceutical and Jasper Therapeutics, and has a patent application with the biotech Immugenia and the biotech Immune Biosolutions. All other authors report no declaration of interests.

Figures

**Fig. 1**
Flow chart of participants meeting the case definition for PIMS.

**Fig. 2. Time series of PIMS hospitalizations from March 2020 to May 2021.**
a Monthly PIMS hospitalizations by region (left). It includes 406 hospitalizations from across Canada (CAN), including 162 from Ontario (ON), 148 from Quebec (QUE), 83 from Western Canada (WEST; 51 from Alberta, 15 from British Columbia, and 17 from Manitoba or Saskatchewan); 13 from Atlantic Canada (ATL; including New Brunswick, Newfoundland and Labrador, Nova Scotia, or Prince Edward Island); and zero from Territories (TER; including Northwest Territories, Nunavut, Yukon). b Weekly PIMS hospitalizations and SARS-CoV-2 cases across Canada (all ages and <20 years separately). PIMS data represent the 3-week moving average of weekly hospitalizations. Week zero is defined as the week beginning March 2, 2020; January 1, 2021, occurs in week 43. SARS-CoV-2 cases were extracted from https://health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19-cases.html, and reflect the date of illness onset.

See this image and copyright information in PMC

References

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Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage

Affiliations

Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous