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Multisystem Inflammatory Syndrome in Children Following the SARS-CoV-2 Delta Variant in Denmark: Clinical Phenotype and Risk by Vaccination Status and Compared to the Pre-Delta COVID-19 Era

20 Pages Posted: 9 Mar 2022

See all articles by Ulrikka Nygaard

Ulrikka Nygaard

University of Copenhagen - Department of Paediatrics and Adolescent Medicine

Mette Holm

Aarhus University - Department of Paediatrics and Adolescent Medicine

Ulla Birgitte Hartling

Odense University Hospital - Department of Paediatrics and Adolescent Medicine

Jonathan Glenthøj

Nordsjaellands Hospital - Department of Paediatrics and Adolescent Medicine

Lisbeth Samsø Schmidt

Herlev Hospital - Department of Paediatrics and Adolescent Medicine

Sannie Brit Nordly

Hvidovre University Hospital - Department of Paediatrics and Adolescent Medicine

Astrid Thaarup Matthesen

Aalborg University Hospital - Department of Paediatrics and Adolescent Medicine

Marie-Louise von Linstow

University of Copenhagen - Department of Paediatrics and Adolescent Medicine

Laura Espenhain

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

More...

Abstract

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C hospitalizations depends on the risk of MIS-C following specific SARS-CoV-2 variants and vaccine effectiveness. 

Methods: This prospective nationwide multicentre cohort study included patients aged 0-17 years in Denmark with MIS-C following the SARS-CoV-2 variant Delta in the period August 1, 2021 to February 1, 2022. The risk of MIS-C was calculated using estimated number of infected individuals by vaccination status. We calculated the incidence rate of MIS-C per 1,000,000 vaccinated and unvaccinated person-years and estimated vaccine effectiveness as 1-IRR (incidence rate ratio) using Poisson regression. Phenotype and risk of MIS-C were compared with MIS-C cases from the first year of the pandemic.

Findings: We identified fifty-one MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The risk of MIS-C was one in 4,000 [95% CI 3,100-5,400] unvaccinated individuals with SARS-CoV-2 variant Delta and one in 15,800 [95% CI 2,800-500,000] vaccinated adolescents with break-through infections. The estimated vaccine effectiveness against MIS-C following the Delta variant was 94% [95% CI; 55%-99%]; p=0·005) in persons aged 5-17 years. The clinical phenotype during the Delta wave was comparable to the pre-Delta era, e.g. hypotension in 57% vs. 50%, respectively.

Interpretation: We found the phenotype and the risk of MIS-C following infection with the Delta variant similar to previous variants. Further, we found a high vaccine effectiveness against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased risk of MIS-C following break-through infection. Knowledge of the risk of MIS-C following different SARS-CoV-2 variants, and the effect of vaccination, is important for estimating MIS-C hospitalizations with new variants, such as Omicron, and in the debate of COVID-19 vaccination of children.

Trial Registration Details: The study was registered at ClinicalTrials.gov (NCT05186597).

Funding Information: The study was funded by a COVID-19 grant from the National Ministry of Higher Education and Science (grant no. 0237-00004B).

Declaration of Interests: None to declare.

Ethics Approval Statement: The study was approved by the Ethics Committee of Capital Region of Denmark (H-20028631) and the Danish Data Protection Agency (P-2019-29). Informed parental consent was provided before participation. A waiver of requirement of informed consent for cases not prospectively enrolled was obtained by the Danish Patient Safety Authority (3-3013-2907/1).

Keywords: Multisystem Inflammatory Syndrome in Children (MIS-C), SARS-CoV-2, variant Delta, incidence, vaccine effectiveness

Suggested Citation

Nygaard, Ulrikka and Holm, Mette and Hartling, Ulla Birgitte and Glenthøj, Jonathan and Schmidt, Lisbeth Samsø and Nordly, Sannie Brit and Matthesen, Astrid Thaarup and Linstow, Marie-Louise von and Espenhain, Laura, Multisystem Inflammatory Syndrome in Children Following the SARS-CoV-2 Delta Variant in Denmark: Clinical Phenotype and Risk by Vaccination Status and Compared to the Pre-Delta COVID-19 Era. Available at SSRN: https://ssrn.com/abstract=4031587 or http://dx.doi.org/10.2139/ssrn.4031587

Ulrikka Nygaard (Contact Author)

University of Copenhagen - Department of Paediatrics and Adolescent Medicine ( email )

Rigshospitalet
Denmark

Mette Holm

Aarhus University - Department of Paediatrics and Adolescent Medicine ( email )

Aarhus
Denmark

Ulla Birgitte Hartling

Odense University Hospital - Department of Paediatrics and Adolescent Medicine ( email )

Odense
Denmark

Jonathan Glenthøj

Nordsjaellands Hospital - Department of Paediatrics and Adolescent Medicine ( email )

Hillerod
Denmark

Lisbeth Samsø Schmidt

Herlev Hospital - Department of Paediatrics and Adolescent Medicine ( email )

Herlev
Denmark

Sannie Brit Nordly

Hvidovre University Hospital - Department of Paediatrics and Adolescent Medicine ( email )

Copenhagen
Denmark

Astrid Thaarup Matthesen

Aalborg University Hospital - Department of Paediatrics and Adolescent Medicine ( email )

Aalborg
Denmark

Marie-Louise von Linstow

University of Copenhagen - Department of Paediatrics and Adolescent Medicine ( email )

Rigshospitalet
Denmark

Laura Espenhain

Statens Serum Institut - Infectious Disease Epidemiology & Prevention ( email )

Copenhagen
Denmark