There is mounting evidence 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 spread to several countries, many of them have been anecdotal to this point. Doctors in a region of Italy hardest hit by the COVID-19 pandemic today released detailed data on a group of 10 children who suffered from an unusual inflammatory disease during the epidemic. , providing strong support for the link. Their report was published Wednesday in The Lancet.
Doctors describe the condition as “Kawasaki-like”, referring to a rare condition 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 case, this can lead to heart problems and aneurysms.
Although it was identified decades ago, the cause of Kawasaki is still unclear. Researchers have widely hypothesized that infectious agents – such as viruses – trigger berserk immune responses in some children with genetic predispositions. But no germline culprits or genetic factors have been firmly established. As such, it is still unclear who will end up suffering from the condition. The researchers only determined that Kawasaki primarily strikes children under the age of five, often boys and often people of Asian and Pacific Islander origin.
Since the start of the pandemic, there have been scattered reports of a recovery in cases of Kawasaki-like illness in children. The cases appear to be linked to COVID-19 outbreaks. However, they do not always correspond to Kawasaki’s “classic” definitions.
In the new Lancet study, Italian doctors offer a clear link between SARS-CoV-2 infection and Kawasaki-like disease. They also detail how the cases they saw differ from classic forms of the disease, laying the groundwork for a specific form of COVID-19 disease.
To do this, doctors examined the medical records of children 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 ravaged by the pandemic.
Doctors identified only 29 cases during this period, of which 19 were diagnosed between January 1, 2015 and February 17, 2020. The other 10 were identified between March 17 and April 14, 2020, while the COVID-19 epidemic was raging. This peak during the epidemic represents a thirty-fold increase in the incidence of the inflammatory condition.
Doctors suspected that all 10 Kawasaki cases during the epidemic had been infected with the new coronavirus, SARS-CoV-2, which causes COVID-19. But only eight of the children tested positive for anti-SARS-CoV-2 antibodies, which are Y-shaped proteins made by the immune system to fight the virus. The presence of antibodies means that the children have been infected. Doctors suspect the other two children of false negatives. One, for example, had received immunoglobulin therapy, 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 have failed to find such a link, the authors argued that together, “this suggests that the coronavirus family may be one of the triggers of Kawasaki disease, SARS – CoV-2 being a particularly virulent strain capable of causing a potent immune response in the host. “
The presence of the virus in almost all cases during the epidemic and the fact that the peak of inflammatory cases “has a clear starting point after the diagnosis of the first case of COVID-19 in our region”, convinced the doctors.
“All of these results and considerations support the hypothesis that the immune response to SARS-CoV-2 is responsible for Kawasaki-like disease in susceptible patients,” they concluded.
Mount the mysteries
But doctors noted that the inflammatory disease was slightly different from that seen in the past. Children affected during the epidemic tended to be older, with an average age of 7.5 years, compared to the 19 pre-COVID cases, who had an average age of 3 years.
The epidemic cases also presented more serious illnesses. Six of the 10 had heart complications, compared to only two of the 19 pre-COVID cases. Two epidemic cases showed signs of toxic shock, which was not observed in any of the previous cases. Finally, eight of the epidemic cases required additional steroid treatment to recover, which was only necessary in three of the pre-COVID cases.
In the end, the doctors were careful to call the cases observed during the epidemic a “Kawasaki” disease.
In an accompanying editorial, Russell Viner, president of the Royal College of Pediatrics, and Elizabeth Whittaker, a pediatric infectious disease specialist at Imperial College London, tried to unravel this. They write: “These differences raise the question of whether this group is Kawasaki disease with SARS-CoV-2 as a trigger, or represents an emerging Kawasaki-like disease characterized by multi-systemic inflammation. “
Like Italian doctors, they point out that, even frightening, this inflammatory disease is still rare, probably affecting no more than 1 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 largely unaffected by COVID-19.
But, note Viner and Whittaker, this insight into what is going on with the immune responses in this rare disease may help explain other mysteries of the disease.
Understanding this inflammatory phenomenon in children could provide vital information about the immune responses to SARS-CoV-2 and the possible correlates of immune protection that might be relevant to adults and children. In particular, if this is an antibody-mediated phenomenon, there could be implications for vaccine studies, which could also explain why some children get very sick with COVID-19, while the majority do not is not affected or asymptomatic.