SARS-CoV-2 Infections Regardless of Severity Linked to Blood Vessel Damage in Children

SARS-CoV-2 appears to cause blood vessel damage in children.

By Emily Shafer

Children have widely been spared of serious symptoms of COVID-19. But, researchers at Children’s Hospital of Philadelphia found that children with SARS-CoV-2 infection, even those with mild or no symptoms, show signs of blood vessel damage that may or may not cause long-term complications.

The study, which appeared in Blood Advances, showed that a high proportion of the children met clinical and diagnostic criteria for thrombotic microangiopathy (TMA), a syndrome that causes small blood clots in the blood vessels. Specifically, they had elevated levels of soluble C5b9, a biomarker of TMA, in their plasma.

TMA has been identified in adults with SARS-CoV-2 infection, but it was unknown whether it affected children. Outside of SARS-CoV-2, TMA — which is commonly seen after hematopoietic stem cell transplants — typically resolves and does not cause any long-term complications. However, in some patients, it can result in later complications, such as kidney damage, high blood pressure, and early heart disease.

David Teachey, MD

“It is concerning that even among kids with minimal to no symptoms of SARS-CoV-2 infection, there are some that meet diagnostic criteria for TMA,” said David Teachey, MD, co-leader of the Immune Dysregulation Frontier Program at CHOP, and co-senior author of the paper. “We don’t yet know the clinical implications of this finding. It’s possible that some children could have long-term complications, but I believe it’s more likely that there will be no long-term consequences, at least in most children.”

Dr. Teachey, also an associate professor of Pediatrics at Perelman School of Medicine at the University of Pennsylvania, and his team analyzed 50 patients with SARS-CoV-2 infection hospitalized at CHOP between April and July 2020. They categorized the patients into three groups: minimal symptoms (21 patients), severe symptoms (11 patients), and patients diagnosed with multisystem inflammatory syndrome in children (MIS-C), a post-viral inflammatory response to COVID-19 (18 patients).

They found elevations in soluble C5b9 in the plasma in patients across all three groups, compared with 26 healthy control patients. Higher soluble C5b9 levels were also linked to higher levels of serum creatinine, which is an indicator of acute kidney injury. Clinical TMA and soluble C5b9 elevation are both associated with renal damage.

Among 19 patients who had complete clinical data available — including a blood smear, complete blood count, and LDH level — 17 patients (89%) met the criteria for TMA, such as elevation in LDH level, and decreases in platelets and hemoglobin.

“The biggest take-home message for me is we still have lots to learn about SARS-CoV-2 in children and adults,” Dr. Teachey said. “We should not make guesses about the short- and long-term impact of infection in children.”

Edward Behrens, MD, co-leader of the Immune Dysregulation Frontier Program and chief of the Division of Rheumatology, and Hamid Bassiri, MD, PhD, attending physician in the Division of Infectious Diseases, were co-senior authors of the paper. Caroline Diorio, MD, a fellow with the Cancer Center, and Kevin McNerney, MD, also a fellow with the Cancer Center, were co-first authors.