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Evidence is accumulating to support a link between COVID-19 and a rare and mysterious inflammatory disease in children, which can be fatal.
Although reports of the new disease have come from various countries, many of them have been anecdotal so far. Now, doctors in an area of Italy most affected by the COVID-19 pandemic have released detailed data on a group of 10 children who experienced an unusual inflammatory disease in the midst of the outbreak, providing strong support for the link. Their report appeared Wednesday in The Lancet.
Doctors describe the condition they saw as “Kawasaki-like,” referring to a rare disease in children that causes inflammation of the blood vessels. Kawasaki disease, identified in Japan in 1967 by Tomisaku Kawasaki, is generally characterized by sustained fever, rash, swelling of the hands and feet, and swollen lymph nodes in the neck. In the worst cases, it can cause heart problems and aneurysms.
Despite being identified decades ago, Kawaski’s cause is still unclear. Researchers have hypothesized that infectious agents, like viruses, trigger frenzied immune responses in certain children with genetic predispositions. But no culprits for germs or genetic factors have been firmly defined. As such, it remains unclear who will end up affected by the condition. The researchers have only determined that Kawaski primarily attacks children under the age of five, often children, and often people of Asian and Pacific Islander descent.
Since the pandemic began, there have been scattered reports of an increase in cases with a Kawasaki-like illness in children. The cases appear to be linked to outbreaks of COVID-19. However, they do not always fit Kawasaki’s “classic” definitions.
In Lancet’s new study, Italian doctors offer a clear connection between SARS-CoV-2 infection and Kawasaki-like disease. They also set out in detail how the cases they saw differ from the classic forms of the disease, laying the groundwork for a specific COVID-19 form of the disease.
Surprising peak
To do that, doctors reviewed the medical records of children who were diagnosed with Kawasaki disease between January 1, 2015 and April 20, 2020, in a hospital in Bergamo, Italy. At the time of the study, the city of Bergamo had the highest rate of COVID-19 infections and deaths in Italy, which was devastated by the pandemic.
Doctors identified only 29 cases in that time period, 19 of which were diagnosed between January 1, 2015 and February 17, 2020. The other 10 were identified between February 18 and April 20, 2020. , as the COVID-19 outbreak spread. The peak during the outbreak represents a thirty-fold increase in the incidence of the inflammatory condition.
Doctors suspected that all 10 Kawasaki cases during the outbreak had been infected with the new coronavirus, SARS-CoV-2, which causes COVID-19. But only eight of the children tested positive for antibodies to SARS-CoV-2, which are Y-shaped proteins produced by the immune system to fight the virus. The presence of the antibodies means that the children had been infected. Doctors suspect the other two children were false negatives. One, for example, had received an immunoglobulin treatment, which may have interfered with the antibody test.
They also noted that previous studies in 2005 and 2014 had also linked coronaviruses, in these cases, those that cause seasonal colds, to Kawasaki disease. Although other studies failed to find that link, the authors argued that, together, “this suggests that the coronavirus family may represent one of the triggers for Kawasaki disease, with SARS-CoV-2 being a particularly virulent strain capable of causing a powerful immunity response in the host. “
The presence of the virus in almost all cases during the outbreak and the fact that the peak in inflammatory cases “has a clear starting point after the first case of COVID-19 was diagnosed in our area,” the doctors convinced. .
“All of these results and considerations support the hypothesis that the immune response to SARS-CoV-2 is responsible for a Kawasaki-like disease in susceptible patients,” they concluded.
Mounting mysteries
But doctors noted that the inflammatory disease was slightly different than cases seen in the past. Children affected during the outbreak tended to be older, with an average age of 7.5 years, compared to 19 pre-COVID cases, who had an average age of 3 years.
Outbreak cases also had more serious illnesses. Six of the 10 had cardiac complications, compared to only two of the 19 cases from the pre-COVID era. Two cases of outbreaks had signs of toxic shock, which was not observed in any of the previous cases. Finally, eight of the outbreak cases needed additional steroid treatments to recover, which was only necessary in three of the pre-COVID cases.
Finally, doctors were careful to call the cases seen during the outbreak a “Kawaski-like” disease.
In an accompanying editorial, Russell Viner, President of the Royal College of Paediatrics, and Elizabeth Whittaker, an expert in pediatric infectious diseases at Imperial College London, attempted to separate this. They write: “These differences raise the question of whether this group is Kawasaki disease with SARS-CoV-2 as the triggering agent, or whether it represents an emerging Kawasaki-like disease characterized by multisystemic inflammation.”
Like Italian doctors, they note that, terrifying though it is, this inflammatory disease is still rare, and likely to affect no more than one in 1,000 children infected with SARS-CoV-2. Parents and doctors should be aware of this, but also keep in mind that children are minimally affected by COVID-19 in general.
But, Viner and Whittaker point out, that insight into what’s happening with immune responses in this rare condition could help explain other mysteries of the disease.
Understanding this inflammatory phenomenon in children could provide vital information about immune responses to SARS-CoV-2 and the possible correlates of immune protection that could be relevant to both adults and children. In particular, if this is an antibody-mediated phenomenon, there may be implications for vaccine studies, and this could also explain why some children become seriously ill with COVID-19, while most are unaffected or asymptomatic.
