May. 16, 2020

Multisystem inflammatory syndrome in children and adolescents with COVID-19

Multisystem inflammatory syndrome in children and adolescents with COVID-19

Scientific Brief

15 May 2020
 

Background

As of 15 May 2020, more than 4 million confirmed cases of COVID-19, including more than 285,000 deaths have been reported to WHO. The risk of severe disease and death has been highest in older people and in persons with underlying noncommunicable diseases (NCDs), such as hypertension, cardiac disease, chronic lung disease and cancer.1-4 Limited data describe clinical manifestations of COVID-19 that are generally milder in children compared with adults,5-8 but also show that some children do require hospitalization and intensive care.9-11

Relatively few cases of infants confirmed to have COVID-19 have been reported; those who are infected have experienced mild illness.7 Robust evidence associating underlying conditions with severe illness in children is still lacking. Among 345 children with laboratory-confirmed COVID-19 and complete information about underlying conditions, 23% had an underlying condition, with chronic lung disease (including asthma), cardiovascular disease, and immunosuppression most commonly reported.12

Recently, however, reports from Europe and North America have described clusters of children and adolescents requiring admission to intensive care units with a multisystem inflammatory condition with some features similar to those of Kawasaki disease and toxic shock syndrome. Case reports and small series have described a presentation of acute illness accompanied by a hyperinflammatory syndrome, leading to multiorgan failure and shock.13-15 Initial hypotheses are that this syndrome may be related to COVID-19 based on initial laboratory testing.  Children have been treated with anti-inflammatory treatment, including parenteral immunoglobulin and steroids.

It is essential to characterize this syndrome and its risk factors, to understand causality, and describe treatment interventions. It is not yet clear the full spectrum of disease, and whether the geographical distribution in Europe and North America reflects a true pattern, or if the condition has simply not been recognized elsewhere.

There is therefore an urgent need for collection of standardized data describing clinical presentations, severity, outcomes, and epidemiology. WHO has developed a preliminary case definition and case report form for multisystem inflammatory disorder in children and adolescents. The preliminary case definition reflects the clinical and laboratory features observed in children reported to date, and serves to identify suspected or confirmed cases both for the purpose of providing treatment and for provisional reporting and surveillance. The case definition will be revised as more data become available. 

Preliminary case definition[a]

Children and adolescents 0–19 years of age with fever 3 days

AND two of the following:                                                  

  1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet).
  2. Hypotension or shock.
  3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP),
  4.  Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).

Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).

AND

Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin. 

AND

No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.

AND

Evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.

Global COVID-19 Clinical Data Platform

WHO has an established platform for standardized, anonymized clinical data. Contributors can enter data into the web-based WHO COVID-19 Clinical Data Platform, which captures all COVID-19 variables listed in the case report forms (CRFs). Using the WHO platform facilitates aggregation, tabulation, and analysis across different settings globally and provides a secure, access-limited, password-protected, electronic database hosted in a secure server at WHO. WHO will maintain appropriate technical and organizational security measures to protect confidentiality and prevent the unauthorized disclosure of the anonymized COVID-19 data.

Note: Contributors will retain control of their data. Health facilities will have access to their dataset in an analyzable format.

How to become a contributor: please email COVID_ClinPlaftorm@who.int and request log-in credentials. The data management team will contact you with instructions for data entry and will assign you a 5-digit site code at that time.

Each CRF has two modules:

1) Module 1 to be completed when multisystem inflammatory syndrome is suspected, and results of tests included in the case definition.

2) Module 2 to be completed at discharge or death.

If the patient is transferred from one ward to another within the same hospital, the CRF should be updated throughout the hospital stay, from the date of admission in the hospital, until the date of transfer to another hospital, discharge from the hospital, or death.

In settings where COVID-19 CRF data have been already entered in databases other than the WHO COVID-19 Clinical Data Platform, WHO will work with health facilities to transfer data from the original databases to the WHO platform. Please email COVID_ClinPlaftorm@who.int to request support. As the COVID data collection is not considered a research study, but rather surveillance of public health importance, patient or parent/guardian consent is not expected to be required in most settings; additionally, information is likely to be collected retrospectively through extraction from medical records in most cases.

Working group members

  • Stephen Freedman, Alberta Children's Hospital Research Institute, University of Calgary, Canada.
  • Shana Godfred-Cato, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Richard Gorman, Department of Health and Human Services, USA.
  • Rakesh Lodha, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
  • Lynne Mofenson, Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA.
  • Srinivas Murthy, BC Children’s Hospital, Vancouver, Canada.
  • Pablo Rojo, Pediatric Infectious Diseases Unit, Hospital 12 de Octubre, Madrid, Spain.
  • Calum Semple, Outbreak Medicine, University of Liverpool, UK.
  • Louise Sigfrid, Centre for Tropical Medicine and Global Health, Oxford University, UK.
  • Elizabeth Whittaker, Paediatric Infectious Diseases and Immunology, Imperial College, London, UK.

 

Additional inputs

  • Rosie Hague, Royal Hospital for Children, Glasgow, Scotland, UK.
  • Yae-Jean Kim, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • Naoki Shimizu, Tokyo Metropolitan Children’s Medical Centre, Japan.
  • Alfredo Tagarro, Hospital Universitario Infanta Sofía, Madrid, Spain.

WHO secretariat

Rajiv Bahl, Ayesha de Costa, Janet Diaz, Karen Edmond, Yasir Nisar, Nigel Rollins.

References

  1. Alqahtani JS, Oyelade T, Aldhahir AM, Alghamdi SM, Almehmadi M, Alqahtani AS, et al. Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PLoS One. 2020;15(5):e0233147. Epub 2020/05/12
  2. Tobacco use and COVID-19. 11 May 2020 Statement. Geneva: World Health Organization (https://www.who.int/news-room/detail/11-05-2020-who-statement-tobacco-use-and-covid-19 accessed14 May 2020)
  3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. Epub 2020/01/28
  4. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. Epub 2020/03/15
  5. Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, et al. A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis. 2020. Epub 2020/03/01
  6. Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol. 2020;55(5):1169-74. Epub 2020/03/07
  7. Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA. 2020. Epub 2020/02/15
  8. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020;382(17):1663-5. Epub 2020/03/19
  9. Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ, Ross CE, McKiernan CA, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020. Epub 2020/05/12
  10. Qiu L, Jiao R, Zhang A, Chen X, Ning Q, Fang F, et al. A Typical Case of Critically Ill Infant of Coronavirus Disease 2019 With Persistent Reduction of T Lymphocytes. Pediatr Infect Dis J. 2020. Epub 2020/05/08
  11. Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. Epub 2020/04/03
  12. Team CC-R. Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. Epub 2020/04/10
  13. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020. Epub 2020/05/11.
  14. DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. J Pediatr. 2020
  15. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Bradley Segal J, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020. Epub 2020/04/09

WHO continues to monitor the situation closely for any changes that may affect this scientific brief. Should any factors change, WHO will issue a further update. Otherwise, this document will expire 2 years after the date of publication.

[a] Consider this syndrome in children with features of typical or atypical Kawasaki disease or toxic shock syndrome.