Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study

Patrick Davies, Claire Evans, Hari Krishnan Kanthimathinathan, Jon Lillie, Joseph Brierley, Gareth Waters, Mae Johnson, Benedict Griffiths, Pascale du Pré, Zoha Mohammad, Akash Deep, Stephen Playfor, Davinder Singh, David Inwald, Michelle Jardine, Oliver Ross, Nayan Shetty, Mark Worrall, Ruchi Sinha, Ashwani Koul, Elizabeth Whittaker, Harish Vyas, Barnaby R Scholefield, Padmanabhan Ramnarayan, Patrick Davies, Claire Evans, Hari Krishnan Kanthimathinathan, Jon Lillie, Joseph Brierley, Gareth Waters, Mae Johnson, Benedict Griffiths, Pascale du Pré, Zoha Mohammad, Akash Deep, Stephen Playfor, Davinder Singh, David Inwald, Michelle Jardine, Oliver Ross, Nayan Shetty, Mark Worrall, Ruchi Sinha, Ashwani Koul, Elizabeth Whittaker, Harish Vyas, Barnaby R Scholefield, Padmanabhan Ramnarayan

Abstract

Background: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).

Methods: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome).

Findings: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 μg/L to 1659 μg/L), and ferritin (1042 μg/L to 757 μg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died.

Interpretation: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown.

Funding: None.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
PIMS-TS admissions per week to UK PICUs, April 1 to May 10, 2020 The cumulative total, and the expected UK cumulative total of similar conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome) from the previous 5 years are shown. PICU=paediatric intensive care unit. PIMS-TS=paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.
Figure 2
Figure 2
Number of patients with PIMS-TS admitted to UK paediatric intensive care units, and percentage receiving individual treatments over time Weeks with fewer than three patients were excluded. Biologic refers to any of anakinra, infliximab, tocilizumab, or retiximab. PIMS-TS=paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.

References

    1. WHO Coronavirus disease (COVID-19) situation report – 162. June 30, 2020.
    1. WHO Coronavirus disease (COVID-19) situation report – 41. March 1, 2020.
    1. CDC Severe outcomes among patients with coronavirus disease 2019 (COVID-19) — United States, February 12–March 16, 2020. March 18, 2020.
    1. Wu Z, McGoogan J. Characteristics and important lessons from the coronavirus disease 2019 outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239–1242.
    1. CDC Coronavirus disease 2019 in children — United States, February 12–April 2, 2020. April 6, 2020.
    1. Parri N, Lenge M, Buonsenso D, Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) Research Group Children with Covid-19 in pediatric emergency departments in Italy. N Engl J Med. 2020 doi: 10.1056/NEJMc2007617. published online May 1.
    1. Tagarro A, Epalza C, Santos M. Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain. JAMA Pediatr. 2020 doi: 10.1001/jamapediatrics.2020.1346. published online April 8.
    1. Shekerdemian L, Mahmood N, Wolfe K. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA Pediatr. 2020 doi: 10.1001/jamapediatrics.2020.1948. published online May 11.
    1. Paediatric Intensive Care Society PICS Statement: increased number of reported cases of novel presentation of multisystem inflammatory disease. April 27, 2020.
    1. Royal College of Paediatrics and Child Health Guidance: paediatric multisystem inflammatory syndrome temporally associated with COVID-19. May 1, 2020.
    1. CDC Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) May 14, 2020.
    1. Jones VG, Mills M, Suarez D. COVID-19 and Kawasaki disease: novel virus and. Novel Case Hosp Pediatr. 2020;10:537–540.
    1. BBC Coronavirus alert: rare syndrome seen in UK children. April 27, 2020.
    1. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–1608.
    1. Verdoni L, Mazza A, Gervasoni A. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771–1778.
    1. Whittaker E, Bamford A, Kenny J. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020 doi: 10.1001/jama.2020.10369. published online June 8.
    1. European Centre for Disease Prevention and Control Rapid risk assessment: paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children. May 15, 2020.
    1. Office for National Statistics 2011 Census: aggregate data [data collection]. UK Data Service. SN: 7427. 2020.
    1. Ramcharan T, Nolan O, Lai CY. Paediatric inflammatory multisystem syndrome: temporally associated with SARS-CoV-2 (PIMS-TS): cardiac features, management and short-term outcomes at a UK tertiary paediatric hospital. Pediatr Cardiol. 2020 doi: 10.1007/s00246-020-02391-2. published online June 12.
    1. Stewart D, Harley J, Johnson M. Renal dysfunction in hospitalised children with COVID-19. Lancet Child Adolesc Health. 2020 doi: 10.1016/S2352-4642(20)30178-4. published online June 15.
    1. Li H, Lui L, Zhang D. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395:1517–1520.
    1. Hall GC, Tulloh LE, Tulloh RM. Kawasaki disease incidence in children and adolescents: an observational study in primary care. Br J Gen Pract. 2016;66:e271–e276.
    1. Burns J, Herzog L, Fabri O. Seasonality of Kawasaki disease: a global perspective. PLoS One. 2013;8
    1. Chang LY, Lu CY, Shao PL. Viral infections associated with Kawasaki disease. J Formos Med Assoc. 2014;113:148–154.
    1. Kanegaye JT, Wilder MS, Molkara D. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123:783–789.
    1. Arons M, Hatfield K, Reddy S. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med. 2020;382:2081–2090.
    1. Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to incidence or outcomes of COVID-19? BMJ. 2020;369
    1. Parslow RC, Tasker RC, Draper ES. Epidemiology of critically ill children in England and Wales: incidence, mortality, deprivation and ethnicity. Arch Dis Child. 2009;94:210–215.
    1. Intensive Care National Audit and Research Centre ICNARC report on COVID-19 in critical care.
    1. Royal College of Paediatrics and Child Health BPSU study—multisystem inflammatory syndrome, Kawasaki disease and toxic shock syndrome.

Source: PubMed

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