Miriam Fine-Goulden: In the eye of an inflammatory storm

When the pandemic started, paediatricians expected to be the spectators or the understudies. We knew from China that covid-19 appeared to spare children, though we didn’t know how or why; we felt reassured that our patient population was not at high risk of critical illness. We, like healthcare teams everywhere, were prepared for a tsunami of critically unwell adult patients and for unprecedented levels of staff sickness.  

As part of the national effort to increase ICU capacity for covid-19 patients, some Paediatric Intensive Care Units (PICUs) were closed to children altogether and beds and staff were freed up to admit adults. Those colleagues have their own stories to tell.  

The closure of beds in other paediatric intensive care units in the region meant that children who would usually be admitted there were transferred to our unit at The Evelina London. All elective paediatric cardiac surgery was put on hold, with only urgent operations scheduled, so the acuity of our caseload shifted. We had a crash course from our adult ICU colleagues on how to care for patients our own size, should our services be required, and were versed in the art of proning. Our rota was re-drafted, shifting vulnerable colleagues from clinical duties, providing night-time on-site presence, and mitigating for the redeployment of some of our medical workforce still-in-training to adult ICU. We moved out of our 20-bedded unit to a smaller area that was still under construction, half of which was designed for ward-level patients, making way for what was to become a 34-bedded adult ICU, and donated a cohort of willing nursing staff. We had a few children with covid-19 disease—one very sick with acute respiratory distress syndrome—but the rest with an apparently less severe course or identified only as an incidental finding. And then the cases started coming.  

Over a ten day period, we admitted eight children with hyperinflammatory shock, with features similar to atypical Kawasaki disease and toxic shock syndrome. [1] All children tested negative initially for SARS-CoV2 on PCR samples (though were found subsequently to be antibody positive on serology). This was an unprecedented cluster which was reported to the local public health authority, but soon escalated as the numbers of cases increased and children were presenting throughout the region.   

What followed felt more like a whirlwind than a tsunami, with rapid multi-disciplinary collaboration, education, and service reconfiguration. Colleagues from PICU, infectious diseases and immunology, cardiology, rheumatology, and pharmacy convened a daily meeting to discuss cases; new teams were established to provide 24/7 imaging, advice and clinical support; resources allocated; clinical areas designated and guidelines created and updated. [2] We admitted almost 50 children fitting the Royal College of Paediatrics and Child Health (RCPCH) case definition for Paediatric multisystem Inflammatory Syndrome Temporally associated with SARS-CoV2 infection (PIMS-TS) to our PICU over a two month period (and around 30 further cases not requiring ICU were admitted to HDU or ward beds). [3]

All of us working at the front line of the covid-19 pandemic have been doing, learning, and teaching simultaneously.  While information dissemination has been rapid, with the proliferation of pre-prints of papers prior to peer review, widespread anecdotal reporting of medical case series and the explosion of information shared via social media, the reliability of data has not always been clear.  Numbers of cases of PIMS-TS in children remain relatively low, and though the evidence base is growing, many PICUs have seen very few and some clinicians have expressed scepticism and disbelief that this is an emerging and distinct entity.  [4,5,6,7,8] What has become apparent is that covid-19, regarded initially as a disease of the respiratory system, is now understood to be a far more complex multi-system inflammatory disorder with a wide spectrum of clinical manifestations beyond respiratory failure.  Though children are not just small adults, there is much to be learned about the pathophysiology of this disease from studying its manifestations in both.  In preparing our response to the pandemic in paediatric intensive care, none of us had foreseen this cytokine storm.

Miriam Fine-Goulden is a consultant in Paediatric Intensive Care at the Evelina London Children’s Hospital and South Thames Retrieval Service, Guys & St. Thomas’ NHS Foundation Trust, and also works for NHS England Specialised Services. She tweets @finegoulden

Competing interests: None declared.

References:

  1. Riphagen S, Gomez X, Gonzalez-Martinez C, et al.  Hyperinflammatory shock in children during COVID-19 pandemic. Lancet May 7th 2020 https://doi.org/10.1016/S0140-6736(20)31094-1
  2. https://www.evelinalondon.nhs.uk/resources/our-services/hospital/south-thames-retrieval-service/pims-ts-paediatric-multisystem-inflammatory-syndrome-temporally-associated-with-sars-cov2.pdf 
  3. https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf 
  4. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet May 13th 2020 https://doi.org/10.1016/S0140-6736(20)31103-X
  5. Belhadjer Z, Meot M, Bajolle F, et al. Pediatric acute heart failure and SARS-CoV-2 infection. Circulation 2020 10.1161/CIRCULATIONAHA.120.048360
  6. Cheung EW, Zachariah P, Gorelik M, et al. Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City.  JAMA June 8, 2020 doi:10.1001/jama.2020.10374
  7. Whittaker E, Bamford A, Kenny J, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2.  JAMA June 8, 2020 doi:10.1001/jama.2020.10369
  8. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescent. NEJM June 29, 2020 doi: 10.1056/NEJMoa2021680