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Blood markers discovered for COVID-linked syndrome in children

Findings from a large, multinational study could help speed development of an accurate diagnostic blood test for the mysterious inflammatory illness.

Tayah Fernandes plays with the same unbridled energy of any other 4-year-old, whooping through an outdoor game of snakes and ladders with her older sister, Brooke, 8, over the recent long weekend.

But just 10 days earlier, she was lying prone in a British hospital bed, fighting for her life, with a rash spread across her face, severe abdominal pain and a spiking fever.

Neither she, her parents, nor the medical team caring for her knew it at first, but Tayah had become the latest patient to be struck with a mysterious syndrome affecting children linked to the coronavirus, at the time known by its unwieldy descriptor, “pediatric multisystem inflammatory system, temporally associated with SARS-CoV-2.”

More of the reporting will air tonight on Nightly News with Lester Holt at 6:30 p.m. ET/5:30 p.m. CT.

The syndrome can, in the most severe cases, cause inflammation of the heart that severely hinders blood flow, requiring intensive care, or aneurysms in a patient’s coronary artery that can induce blood clots. During recent weeks the syndrome has led to the deaths of several children and teenagers on both sides of the Atlantic, in countries most seriously affected by the coronavirus pandemic.

Discovering blood markers

But early identification can help to prevent these deadly outcomes, doctors say, and there was an important diagnostic advance this past weekend, spearheaded by a 30-person research team operating inside a cluster of London laboratories in the same complex where Alexander Fleming discovered penicillin.

A large-scale comparison study they initiated of the most critically ill children confirmed that this new mysterious syndrome has measurably different blood and infection markers from other rare conditions, like Kawasaki disease and staphylococcal toxic shock syndrome, to which it has been repeatedly compared and with which it shares several of the most severe symptoms.

These new findings will help accelerate a European Union-funded project that aims to identify the disease’s molecular signature, which is necessary for the development of an accurate diagnostic blood test.

Four year-old Tayah Fernandes while in hospital with a new disease linked to coronavirus.
Four year-old Tayah Fernandes while in hospital with a new disease linked to coronavirus.Courtesy Fernandes Family

But Tayah’s mother, Shannon Fernandes, 27, a care-worker at a nursing home near her home in the English town of Stalybridge, knew little about COVID-19 when she tested positive for it in mid-April, and had never heard of Kawasaki or the staphylococcus bacteria.

In mid April, she endured several days of high fever and temporarily lost her sense of taste and smell, but she recovered sufficiently to return to work after the mandated 14 days of isolation at home with her family.

Then at the start of May, Tayah told her parents her “belly” hurt. Primary care doctors told Shannon and husband, Alex, during telephone consultations that Tayah likely just had constipation, and they prescribed mild pain medication.

But when Tayah continued to complain of stomach pains and could barely eat, Shannon followed her “mother’s instinct” and took her to the nearest emergency room.

Full coverage of the coronavirus outbreak

“When it got to like day five, I knew nothing had changed,” she recalled. “It was only getting worse.”

Once she arrived at their local hospital, according to the family’s account, some senior doctors contacted by phone continued to push the earlier diagnosis of constipation. But the physician who attended to Tayah in person was sufficiently concerned that she insisted on blood tests, Shannon said.

"It was only that one doctor who fought my corner and said, ‘I'm not happy with the way Tayah looks, I'm doing the test myself,’ because nobody else would.”

The second of those tests highlighted some sky-high infection markers in the young girl’s blood, prompting doctors to proscribe antibiotics to treat what the test results had implied was a bacterial infection. But these had little effect, and her condition only worsened.

“The temperatures were going higher, weren't coming down with any medication,” Shannon said. “That's when they got worried, and they phoned for advice.”

Dr. Elizabeth Whittaker, infectious disease and immunology consultant and clinical lecturer at Imperial College London.
Dr. Elizabeth Whittaker, infectious disease and immunology consultant and clinical lecturer at Imperial College London.NBC News

Hundreds of doctors around the world have faced a similar quandary in recent weeks, as children and young adults have arrived in their wards presenting a combination of symptoms that do not fit an existing diagnostic pattern and often do not respond to what seem like appropriate treatment.

Several of the most serious cases admitted to the intensive care unit at central London’s St. Mary’s Hospital in early April had puzzled Dr. Elizabeth Whittaker, 41, an infectious disease and immunology consultant and clinical lecturer at Imperial College London.

After comparing notes with a counterpart at another hospital, who had also seen several similar patients, she rang one of the world’s most experienced pediatric infectious disease doctors, Mike Levin, 68, a professor who chairs the International Child Health team at Imperial.

Over the course of a single, lengthy conversation, the two — along with a third colleague — hatched a plan to approach the British government’s health service officials who focus on pediatric care.

Professor Mike Levin chairs the International Child Health team at Imperial College London.
Professor Mike Levin chairs the International Child Health team at Imperial College London.NBC News

Those authorities responded swiftly to their concerns and asked them to convene a group of infectious disease and intensive care experts to review 38 of these cases across several London hospitals. By the end of April, the U.K.’s leading pediatric authority, the Royal College, had issued an alert based on their findings.

“We started to be contacted by pediatricians in many other hospitals and many other countries,” said Levin, a soft-spoken South African who looks a decade younger. “In very quick succession, there were reports from all the countries that had had large cases of COVID-19 — so Spain, Italy, France and now the United States.”

Levin and Whittaker spent the days that followed on Zoom calls with global peers, explaining what they had discovered, sharing information and best practices, while continuing to juggle their regular clinical and research duties.

By mid-May, as Tayah Fernandes’ sickness peaked, the Center for Disease Control and Prevention issued a fresh health alert to U.S. doctors, warning about the syndrome — which it called “multisystem inflammatory syndrome in children,” or MIS-C — that had by then appeared in around 110 cases in New York state and a further 18 states nationwide.

The following day, May 15, the World Health Organization issued guidance for the new inflammatory syndrome, listing its most common symptoms, highlighting apparent links to COVID-19 and urgently demanding the collection of standardized data for analysis.

Levin’s team had already started working on the beta version of a global database, and he — like other doctors involved — described to NBC News an unmatched level of international co-operation across national boundaries and disciplines, as they raced against time to improve their understanding of this condition.

“The last two months have been the most challenging, unusual, that I've had in my career,” said Levin. “It's been a huge learning curve.”

He said that around a third of the children afflicted by this syndrome in the British review had tested positive for COVID-19, and a significant number of the rest had tested positive for the coronavirus antibodies.

Four year-old Tayah Fernandes while in hospital with a new disease linked to coronavirus.
Four year-old Tayah Fernandes while in hospital with a new disease linked to coronavirus.Courtesy Fernandes Family

One of the next steps will be seeking to understand if there is a causal relationship between the syndrome and coronavirus rather than simply a coincidental correlation, he said, and a detailed examination of why only some children suffer from its most serious symptoms.

For clinicians, the focus will remain on identifying the syndrome as early as possible, and conducting trials on various treatments to see which are the most effective.

And the lesson for parents, say Alex and Shannon Fernandes, is the need to seek second opinions and in-person consultations if possible, even at a time when authorities continue to publicize that hospitals are under tremendous pressure.

“I don't wish it upon anybody's children,” said Alex Fernandes, 31. “What we've been through the last nine days with Tayah, you don't wish upon any, any child. It was awful.”