By Joe Pinkstone for MailOnline, May 14, 2020
Scientists have found the first clear evidence that coronavirus infection causes the Kawasaki-like inflammatory condition that affects children.
A study of eight children admitted to a hospital in Birmingham with the condition reveals that they were infected with the SARS-CoV-2 virus several weeks before they showed symptoms.
All children had been tested negative in the traditional laboratory test used to diagnose COVID-19 in adults.
However, a tailor-made antibody test showed that the young patients were infected with the coronavirus and produced antibodies to fight the pathogen.
Doctors who have treated the children say that antibody tests are the only way to accurately identify the presence of the virus in children suffering from the hyperinflammatory condition, which can be fatal.
It remains unknown why the syndrome develops weeks after infection, but scientists believe it may be due to a serious overreaction of the body’s own immune system.
This ‘immune-mediated pathology’ causes the immune system to become confused and can damage the body’s own cells.
A similar phenomenon has been observed in adults and can be fatal for the sickest patients.
Bertie Brown was admitted to Worcestershire Royal Hospital on his second birthday last month after developing a fever and rash all over his body
The syndrome in children is provisionally called PIMS-TS, for “pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2”.
However, the British scientists say the definition of the condition is incorrect because it is not ‘temporarily associated’ with the pandemic, but is instead ’caused by a SARS-CoV-2 infection’.
A team of scientists led by Dr. Alex Richter and Professor Adam Cunningham of the University of Birmingham studied eight young patients who were hospitalized between April 28 and May 8.
Lab tests – used to identify COVID-19 and also to screen health professionals – came out negative for all eight individuals.
These tests, called PCR tests, are extremely reliable and “come closest to a gold standard for determining active infection.”
Professor Adam Cunningham, who led the study with Dr. Alex Richter and Dr. Barney Scholefield, told MailOnline: “The PCR records the presence of the virus itself, so the virus must be present in the throat where the sample is (a throat swab is usually taken).
“If you clear up the infection, there is no virus to detect.
‘In response to infections, we often produce antibodies, which are usually detectable from 14 days after the first infection.
“These antibody responses often stay in the body for months and many years after that.”
The mean age of the hospitalized children was nine years and five of the patients were boys.
Chloe Knight, 22, revealed that her two-year-old son, Freddie Merrylees (pictured), fell ill just before the closure and was ‘like a zombie’ because of Kawasaki disease. The youngster had a rash on his body, high temperature, red eyes and had difficulty eating and drinking
Seven of the patients showed symptoms of both hyper-inflammation and Kawasaki disease.
One of the patients showed symptoms of hyper-inflammation and some signs of toxic shock syndrome.
The mysterious and dangerous condition has been described by top medical professionals as very rare, and symptoms can include fever, abdominal pain, rash, and red lips and eyes.
A very small group goes into shock, affecting the heart, and they can get cold hands and feet and breathe quickly.
Of the eight children treated and studied in Birmingham as part of this historical study, all patients had a fever and at least one gastrointestinal symptom such as abdominal pain, vomiting and diarrhea.
Six of the patients had to be admitted to the pediatric intensive care unit because of heart-related problems and low blood pressure due to the disease.
They all showed positive signs after treatment and have since been discharged from the ICU.
Due to media reports and claims by leading advisers and leading politicians that this condition may be related to the coronavirus pandemic, the researchers took blood samples from all eight children.
They then developed a modified antibody test with the help of researchers from the University of Southampton.
The test involves making an artificial copy of a key protein on the surface of the coronavirus that resembles a peak.
This unique ‘peak’ is an important identification of the killer virus and was first revealed in detail by Professor Max Crispin of the University of Southampton.
He modeled the surface peaks of the protein and this allowed his team to make an almost exact copy of the peak.
At the Birmingham hospital, this artificially created version of the protein peak was mixed with blood samples from the patients.
The researchers saw that some antibodies in the children’s blood were attached to the nail, just as they would if the virus itself invaded.
In the tests, researchers looked to see which of three different immunoglobulins (the technical name for an antibody) – IgG, IgA, and IgM – were trapped on the imitation virus.
A positive IgM reading in the tests indicates a recent infection, while a positive reading for IgG and IgA shows an older infection, the scientists say.
The children in the hospital in Birmingham did not have IgM antibodies, but did have IgG and IgA antibodies, showing that they had been infected with SARS-CoV-2 several weeks earlier.
This delay is the reason the PCR test failed to detect the infection, the researchers say.
“IgM was not detected in children, which contrasts with adult hospitalized adult COVID-19 patients, all of whom had positive IgM responses,” the researchers write in the study, which was submitted to a preprint server and are by MailOnline.
“For antibody responses, IgM responses first develop, before eventually diminishing and then IgG responses dominate,” the researchers explain.
Thus, high IgG levels in the absence of IgM usually indicate infection weeks or even months earlier. ‘
This antibody test is performed in a laboratory and is not a portable test. It is also fundamentally different from the test approved by the government today and manufactured by Roche.
Roche’s method uses a nucleoprotein to mimic the SARS-CoV-2 virus, not the viral peak.
“Using the native-like viral peak for antibody testing appears to be a very sensitive way to detect exposure to SARS-CoV-2,” Professor Crispin told MailOnline.
The researchers say their study shows that the only way to diagnose patients with symptoms of severe inflammatory syndrome who have tested negative for the PCR is through antibody testing.
Dr. Cunningham says, “In our study, none of the children were positive by PCR, but all children were positive by antibody testing.
“This could mean that the disease started after the kids already removed the virus.
If so, serology may be more diagnostic for children who are PCR negative.
“What the antibody test tells us is that these children have certainly been infected with SARS-CoV-2 in the past, which will hopefully help doctors make decisions about treating these patients.
Ultimately, both PCR and antibody tests play overlapping roles in diagnosing this syndrome. Very exciting, the detection of the antibodies can also provide clues as to how this syndrome develops. ‘
As a result of their findings, the researchers propose to modify the definition of PIMS-TS, as the Kawasaki-like state is now known.
Since all patients were serologically positive, it may be worthwhile to change the definition of PIMS-TS so that TS is not only ‘temporarily associated with SARS-CoV-2 pandemic’ but ’caused by a SARS-CoV- 2 infection, ‘the researchers conclude in their study.