Enlarge /. The Boston Medical Center children's life specialist, Karlie Bittrich, looks after a baby while she is being set up on April 29, 2020 in a pediatric tent outside of the Boston Medical Center in Boston.
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There is plenty of evidence to suggest a link between COVID-19 and a rare, mysterious inflammatory disease in children that can be life-threatening.
Although reports of the new disease have been received from several countries, many of them have been anecdotal so far. Now doctors in an area most affected by the COVID-19 pandemic in Italy have released detailed data on a group of 10 children who had an unusual inflammatory disease during the outbreak, which solidly supports the connection. Her report appeared on Wednesday in The Lancet.
Doctors describe the condition they saw as "Kawasaki-like" and refer to a rare disease in children that causes inflammation of the blood vessels. Kawasaki disease, identified by Tomisaku Kawasaki in Japan in 1967, is typically characterized by persistent fever, rash, swelling of the hands and feet, and swollen lymph nodes in the neck. In the worst case, heart problems and aneurisms can occur.
Although Kawasaki was identified decades ago, the cause is still unclear. Researchers have generally believed that infectious agents, such as viruses, trigger insane immune responses in certain children with a genetic predisposition. But not a single culprit or genetic factor was pinned down. Therefore, it is still unclear who will be affected by the disease. Researchers have only found that Kawasaki mainly affects children under the age of five, often boys, and often people of Asian and Pacific origin.
There have been isolated reports of an increase in cases with a disease similar to Kawasaki in children since the pandemic began. The cases appear to be associated with outbreaks of COVID-19. However, they do not always match the "classic" definitions of Kawasaki.
In the new Lancet study, Italian doctors offer a clear link between infection with SARS-CoV-2 and the Kawasaki-like disease. They also detail how the cases differ from the classic forms of the disease and lay the foundation for a COVID-19 specific form of the disease.
To this end, the doctors checked 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 hit by the pandemic.
Doctors identified only 29 cases during this period, 19 of which were diagnosed between January 1, 2015 and February 17, 2020. The other 10 were identified between March 17 and April 14, 2020, when the COVID 19 outbreak raged. This peak during the outbreak signifies a thirty-fold increase in the incidence of the inflammatory condition.
The doctors suspected that all 10 Kawasaki cases during the outbreak were infected with the new SARS-CoV-2 coronavirus that causes COVID-19. But only eight of the children tested positive for SARS-CoV-2 antibodies, which are Y-shaped proteins made by the immune system to fight the virus. The presence of the antibodies means that the children were infected. The doctors suspect that the other two children were false negative. For example, one had received immunoglobulin treatment that may have disrupted the antibody test.
They also found that previous studies from 2005 and 2014 also linked coronaviruses – in those cases, those that cause seasonal colds – to Kawasaki disease. Although other studies found no such connection, the authors argued that "together, this indicates that the coronavirus family could be one of the triggers of Kawasaki disease, with SARS-CoV-2 being a particularly virulent strain that has a strong immune system can trigger response in the host. "
The presence of the virus in almost all cases during the outbreak and the fact that the increase in inflammatory cases "has a clear starting point after the first case of COVID-19 was diagnosed 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 a Kawasaki-like disease in susceptible patients," they concluded.
More and more secrets
However, the doctors found that the inflammatory disease was slightly different from the cases observed in the past. The children affected during the outbreak tended to be older with an average age of 7.5 years than the 19 cases before COVID with an average age of 3 years.
The outbreak cases also had more serious illnesses. Six of the ten cases had heart complications compared to only two of the 19 cases prior to COVID. Two outbreaks showed signs of toxic shock that was not seen in any of the previous cases. Finally, eight of the outbreak cases required additional steroid treatment to recover, which was only necessary in three cases before COVID.
Ultimately, the doctors took care to call the cases observed during the outbreak a "Kawasaki-like" disease.
In an accompanying editorial, Russell Viner, president of the Royal College of Pediatrics, and Elizabeth Whittaker, an expert in pediatric infectious diseases at Imperial College London, tried to tell the difference. They write: "These differences raise the question of whether this cluster is a Kawasaki disease with SARS-CoV-2 as a trigger or an emerging Kawasaki-like disease that is characterized by multi-system inflammation."
Like the Italian doctors, they emphasize that this inflammatory disease, however scary it may be, is still rare and probably does not affect 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 only minimally affected by COVID-19.
However, Viner and Whittaker note that insight into the processes with immune responses in this rare condition could help explain other secrets to the disease.
Understanding this inflammatory phenomenon in children could provide important information about immune responses to SARS-CoV-2 and possible correlates of immune protection that could be relevant for both adults and children. In particular, if it is an antibody-mediated phenomenon, it can affect vaccine studies, and it could also explain why some children get COVID-19 very badly while the majority are unaffected or asymptomatic.