Kawasaki Link to COVID-19 in Kids Probed as UK, New York Issue Alerts

Pediatricians, immunologists, and cardiologists are keeping close watch on pediatric cases that look similar to Kawasaki syndrome following reports that draw a tenuous link between the inflammatory arterial disease and COVID-19 in children.

In the United Kingdom, the Royal College of Paediatrics and Child Health released guidance on May 1, 2020, describing a “pediatric multisystem inflammatory syndrome temporally associated with COVID-19.” The document stresses that while most children infected with SARS-CoV-2 are asymptomatic or exhibit only mild symptoms, “in the last 2 months a small number of children have been identified who develop a significant systemic inflammatory response” that “shares common features with other pediatric inflammatory conditions including: Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes.”

On May 4, New York City’s department of health also issued a note alerting physicians that the same “pediatric multisystem inflammatory syndrome” first reported in the UK is also being seen among children and young adults in the United States. So far, 15 cases have been identified in the city’s hospitals, the alert notes.

“Clinical features vary, depending on the affected organ system, but have been noted to include features of Kawasaki disease or features of shock; however, the full spectrum of disease is not yet known,” writes Demetre C. Daskalakis, MD, MPH, deputy commissioner of the Division of Disease Control, New York City Department of Health and Mental Hygiene. “Persistent fever and elevated inflammatory markers (CRP, troponin, etc) have been seen among affected patients. Patients with this syndrome who have been admitted to pediatric intensive care units (PICUs) have required cardiac and/or respiratory support. Only severe cases may have been recognized at this time.”

In Italy, pediatric cardiologist Giovanni Di Salvo, MD, PhD (University of Padua, Italy), has seen two cases of “atypical Kawasaki,” he told TCTMD: one in a 12-year-old, the other in a 15-year old. The younger had a dilated left main coronary artery, fever, abdominal pain, and high troponin. Echocardiography showed myocardial inflammation and hypokinesis at the cardiac apex.

The 15-year-old was admitted with high troponin, antiphospholipid syndrome, fever, cutaneous rash, strawberry tongue, and no arterial inflammation but hypokinesis and edema at the level of the apex seen on echo and cardiac MR.

Di Salvo, who is in touch with European colleagues about these cases, said he believes more will come to light.

Worth Watching

Diagnosis of classic Kawasaki is made on the basis of fever lasting more than 5 days, plus four out of five diagnostic criteria including erythema of the lips or mouth, trunk rash, swelling or erythema of the hands or feet, conjunctivitis, and lymph node swelling. Kawasaki vasculitis, which is more common in untreated cases, is the leading cause of acquired cardiovascular disease in children in developing countries.

Speaking with TCTMD, Tarek Alsaied, MD (Cincinnati Children’s Hospital, OH), a member of the American College of Cardiology’s Adult Congenital and Pediatric Cardiology Council, stressed that Kawasaki disease is rare and treatable, typically with aspirin and intravenous immunoglobulins. The “vast majority” of kids recover, he noted. “Interventional cardiologists are aware of Kawasaki disease, because 2% of patients develop aneurysms and some can develop myocarditis and decreased contractility and, in severe cases, heart failure.”

Only one case report linking COVID-19 to a case of Kawasaki disease has been published to date, Alsaied told TCTMD. This is a preprint report in Hospital Pediatrics describing a 6-month-old infant diagnosed with Kawasaki who also tested positive for COVID-19. After being discharged from hospital following treatment for Kawasaki, the girl, who then stayed in 14-day quarantine at home, had only minor COVID-19 symptoms and no respiratory distress. No acute vasculitis was reported, although the authors note that cardiac involvement typically occurs after the initial presentation and follow-up echocardiography is planned.

Whether COVID-19 was causal in this published case, or a coincidental diagnosis, is unclear, said Alsaied. He pointed out that Cincinnati Children’s gets a lot of Kawasaki referrals as a large, regional pediatric hospital. “What we started doing is testing them for COVID-19 because many of them are having fever and having respiratory symptoms, and because of these reports” from the UK and New York, he said. “So far, for the last week or so, we haven't seen anyone test positive [for COVID-19] who has Kawasaki disease, but this is something that we're watching closely.”

Alsaied is following the UK reports of atypical Kawasaki disease and notes that while some of these cases tested positive for SARS-CoV-2, others have not. But an unanswered question is whether the currently used COVID-19 tests are sensitive enough in children.

“Most of the testing that we have is based on studies in older people, and you do need the patient to be cooperative to get a good swab,” he commented. “So it is possible that with kids, they either have different concentrations of the virus or they may not be very cooperative while doing the testing, so the test may have less sensitivity. But I'm not aware of any studies that have looked at this question.”

Of the two patients seen by Di Salvo, the younger tested positive for COVID-19 following a nasopharyngeal swab, but the older patient did not. Subsequent retesting using immunoglobulin G (IgG) was, in fact, positive. IgG testing, he said, may be needed for these Kawasaki-like cases turning up in children who test negative for the virus. He points out that had the 15-year-old patient not had elevated troponin, the patient would not have been sent for echo and the cardiac abnormalities would have been missed.

According to Alsaied, only 2% of confirmed COVID-19 cases have been in children and, of these, a small minority develop more than moderate illness. However, the focus has been on the acute setting.

“Compared with adults, kids seem to be more protected, but whether or not this triggers an inflammatory syndrome and may cause them to develop more severe Kawasaki disease is unknown at this point,” he said. “The bottom line is we've been watching this very closely in the pediatric community, we've started testing patients who are diagnosed with Kawasaki disease for COVID-19, and it is something to be aware of,” Alsaied said. “The upcoming weeks will be more telling as to whether we find a real association or if it's just a coincidence that some patients with Kawasaki disease have been testing positive for COVID-19. Precautionary measures, such as testing patients with Kawasaki for COVID-19, has been our practice to make sure that we understand this association better.”

Di Salvo stressed the need to be vigilant, even in the setting of negative tests, since this could be a case of false negatives in young patients who have already cleared the virus. Cases of atypical Kawasaki cropping up may reflect an asymptomatic course of the viral illness, followed 3 to 4 weeks later by an inflammatory syndrome similar to Kawasaki. While it’s “very early” to connect the dots, he said, “if we want to be safe right now, we can say this is a Kawasaki-like syndrome correlated with COVID-19, but it is very early and if you don’t do the echo, most likely you will miss the cardiac involvement.