Does SARS-CoV-2 cause Kawasaki disease in children?
by Michael J. Bell, MD
Kawasaki disease was first characterized in the late 1960s and was previously called “mucocutaneous lymph node disease.” Recently, hospitals in several countries have reported children with Kawasaki-like symptoms possibly associated with COVID-19. We have seen a few cases at my hospital, and they can be quite challenging.
The etiology of Kawasaki disease (KD) has never been fully known. Several aspects point to an infectious cause, including the relatively short nature of the acute illness (which mimics other viral infections of childhood) and the geographic nature of outbreaks where a number of cases is identified in a city or town. It occurs in children aged older than 3 months — suggesting that there might be maternal antibodies that are protective in the youngest infants. And it does not happen to adults — suggesting that adults may have already been exposed to the pathogen and therefore do not get the disease.
However, some experts have argued that a number of the characteristics are not related to infection. For example, children of Asian heritage have a much higher incidence compared with other races or ethnicities. And although there are outbreaks in regions, these outbreaks tend not to be in the same household or same day care centers — again, implying that infection with a virus or something else alone is insufficient to cause the disease.
The symptoms of true Kawasaki disease (not associated with COVID-19) are:
- fever for at least 5 days;
- four of the following five features: changes in extremities (redness or swelling of palms of hands or soles of feet early in the disease, and peeling of skin on these regions later in the disease); diffuse rash, often starting on the trunk; conjunctival injection (ie, redness of the eyes) without any discharge; redness or cracking of the lips/tongue; swollen lymph nodes in the neck, often only on one side;
- and exclusion of other causes.
These symptoms arise because medium-sized arteries become inflamed. In severe cases, patients with KD can have low blood pressure and shock — and this severe manifestation seems to be quite prevalent in the series of cases that are now being reported in Europe and in the United States that may be related to SARS-CoV-2 infection.
The reason why Kawasaki disease is important to diagnose is because of the possible treatment and sequelae.
Because the medium-sized arteries are inflamed in this condition, it has been known for decades that patients with KD are at risk for developing aneurysms within the arteries of the heart. In one textbook, untreated KD resulted in 25% of children with coronary artery aneurysms — which obviously puts them at risk for coronary artery events like heart attacks and ischemia as they grow up. The recommended treatment for KD (again, not related to COVID-19) is to give IV immunoglobulin. Again, because the precise mechanism of the inflammation is not known, it is not completely clear how this is helpful. But the theory behind its use is that administration of IVIG leads to decreased inflammation and a cessation of the process within the arteries. Studies have demonstrated that using this treatment leads to a significant decrease in the number of children who develop coronary artery aneurysms.
It is unclear if the SARS-CoV-2 virus, which causes COVID-19, causes “typical” Kawasaki disease or some syndrome that is only mimicking it. The European clinicians are reporting that some of their patients have developed coronary artery problems — so we suspect it is causing something as serious in the long term as normal KD. In addition, patients with COVID-19-related KD (or KD-like symptoms) have been much more severely ill. As I said earlier, the shocklike state that is pretty rare in true KD is certainly being seen in these COVID-19 cases. So, both of these characteristics make this condition important for frontline clinicians to have in their minds as they take care of children with COVID-19.
How SARS-CoV-2 causes KD is unclear. It is clear that COVID-19 is a very inflammatory condition — with adults with COVID-19 demonstrating cardiovascular collapse and shock, significant inflammation in their lungs and other organs and a very high incidence of blood clots in the vasculature. There are fewer overall cases of COVID-19 in children at the moment. But the children we are taking care of also demonstrate quite a bit of inflammation. The fact that SARS-CoV-2 might lead to an inflammatory state that causes KD makes a lot of intuitive sense. But we need to see how all of this evolves.
Disclosures: Bell reports no relevant financial disclosures.
For more information:
Michael J. Bell, MD, is the chief of critical care medicine at Children’s National Hospital in Washington, D.C. He can be reached via Jamel Langley, MPS, at email@example.com.