COVID-19 and pediatric stroke—is there a connection?

May 13, 2020

By Heather Fullerton.

One of our earliest pediatric mechanical thrombectomy cases at UCSF Benioff Children’s Hospital was during the 2003 SARS global outbreak.  Some of you may remember how children suffered more severe respiratory illnesses with that other coronavirus, and how thrombophilia was an anecdotal feature of the disease.  A toddler in our pediatric ICU with SARS pneumonia developed a large clot in her left ventricle.  While agitated during an IV placement, she suddenly stopped moving the right side of her body: the clot was gone from her heart, and instead she had complete blockage of her basilar artery and left internal cerebral artery.  Our interventional neuroradiologists successfully removed the clots—despite the more primitive devices of the day—and she survived with moderate motor deficits.

That case made me interested in the role of infection as a trigger for childhood arterial ischemic stroke, and ultimately led to our IPSS-run multicenter VIPS (Vascular effects of Infection in Pediatric Stroke) study.  Many of you helped enroll the >700 children in the VIPS study that demonstrated that minor acute infections—mostly upper respiratory infections—transiently increase stroke risk.  Infection can trigger cardioembolic stroke in children predisposed by congenital heart disease; it can also trigger arteriopathic and idiopathic stroke in otherwise healthy children. Many of the infections preceding pediatric stroke were subclinical.   So…what about COVID-19?  In early April, we began to see reports of COVID-related thrombophilia in adults, reminiscent of 2003 SARS.  An April 29th letter to the New England Journal of Medicine described a flurry of young adults in New York with ischemic strokes after mild or asymptomatic infection.  Our dermatology colleagues began seeing children with post-COVID “pernio-like” ischemic lesions of distal toes, thought to be a small-vessel vasculitis. And now, in early May, we are seeing reports of a severe hyperinflammatory condition in children with COVID-19 leading to vasogenic shock; a British case series includes one such child with a fatal cardioembolic stroke while on extracorporeal life support.

The VIPS II study has been enrolling new pediatric stroke cases over the past three years with the aim of identifying the specific pathogens triggering childhood stroke; it will use next-generation sequencing of nucleic acids to identify pathogens in throat swabs and blood samples. We successfully obtained permission to continue enrolling in VIPS II through the COVID-19 pandemic, so hope to learn more about this new coronavirus, SARS CoV-2, as a pediatric stroke trigger.  In the meanwhile, we will be following the literature closely and blogging about relevant emerging evidence.  Please let us know if you become aware of any COVID-related pediatric strokes, or new papers that we might have missed.  And consider submitting an IPSO blog post yourself!

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Links to Relevant Scientific Publications:

VIPS paper on clinical infections as a trigger for childhood stroke
https://www.ncbi.nlm.nih.gov/pubmed/26423434

VIPS paper on subclinical herpesvirus infection as a trigger for childhood stroke
https://www.ncbi.nlm.nih.gov/pubmed/26813104

Papers on thrombotic complications in adult patients with coronavirus infections
https://www.ncbi.nlm.nih.gov/pubmed/32305883
https://www.ncbi.nlm.nih.gov/pubmed/32291094

Early publication on pernio-like lesions in children after COVID-19
https://www.ejpd.com/images/acroischemia-ENG.pdf?fbclid=IwAR0BRRl6pX0DwD7RzQKI-Nbgo-LkfSYgGGA8maMtY7fh2BMjU6Sqmzle6BY

Stroke in young adults with COVID-19
https://www.nejm.org/doi/10.1056/NEJMc2009787

British series of children with COVID-19 hyperinflammatory shock, including one with an cardioembolic stroke
https://www.sciencedirect.com/science/article/pii/S0140673620310941?via%3Dihub

Links to Relevant Lay Press Articles:

CNN Health article describing five young adults with COVID-19 related ischemic strokes at Mount Sinai Hospital in New York (April 23, 2020)

Heather Fullerton, MD, MAS

Heather Fullerton, MD, MAS

Heather Fullerton, MD, MAS, is a pediatric vascular neurologist and Chief of Neurology at UCSF Benioff Children’s Hospital in San Francisco, California.  She has been a member of the International Pediatric Stroke Study (IPSS) since 2002 and is the inaugural president of IPSO.  She is grateful to everyone who has joined the IPSO effort and believes in the mission of improving the lives of children with cerebrovascular disease worldwide. 

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