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Source: COVID-19 News  Oct 18, 2020  10 days ago
BREAKING! COVID-19 News: Mutated SARS-CoV-2 Strain D839Y/N/E With Super Antigens Inserts Identified As Cause Of Multi-Inflammatory Syndrome MIS-C And MIS-A
BREAKING! COVID-19 News: Mutated SARS-CoV-2 Strain D839Y/N/E With Super Antigens Inserts Identified As Cause Of Multi-Inflammatory Syndrome MIS-C And MIS-A
Source: COVID-19 News  Oct 18, 2020  10 days ago
COVID-19 News: Researchers from University of Pittsburgh, Cedars-Sinai Medical Center-Los Angeles and Martin Luther University Halle-Wittenberg-Germany have in a new study discovered that a mutation strain of the SAR-CoV-2 called D839Y/N/E that has a unique superantigenic insert in the spike region and is able to generate a hyperinflammatory syndrome reminiscent of toxic shock syndrome (TSS) in individuals causing the condition known as multi inflammatory syndrome in children (MIS-C) and also in adults (MIS-A). The strain also causes the T-Cells in the human host to be skewed and ‘mutilated.’

The study findings were published in the peer reviewed journal: PNAS  (Proceedings of the National Academy Of Sciences of the United States Of America) https://www.pnas.org/content/117/41/25254
This article is a series of that Thailand Medical News will be featuring on the various emerging mutated strains and how they are changing the course of the COVID-19 pandemic into something that is becoming more complex and difficult to manage. Thailand Medical News has been and is working with numerous research groups globally in tracking, identifying and understanding the various mutated strains despite being scorned on in the beginning by numerous stupid entities who ridiculed our claims of more emerging  potent SARS-CoV-2 mutations and also on the concept of personalized medicine approach to treat SARS-CoV-2 as every strain has unique properties and pathogenic paths of its own. Besides this strain, we also have identified 3 other strains with other research groups that have unique and distinct pathogenic paths.(we will be featuring those in the coming days.)
The D839Y/N/E strain was on was not on the radar on most genome tracking sites as there has been no proper constant genomic sequencings and also monitoring of prevalence, something that health authorities have to start making mandatory.
The strain originated from Europe most probably from Italy and is now gradually appearing more and more in UK, Italy, Spain, France and United States.
The first appearance of the strains were when infected COVID-19 children in the Italy started developing conditions similar to the Kawasaki syndrome and then as more cases started to also appear in the United States, more attention was paid to the condition and researchers later termed the condition as Multi-Inflammatory Syndrome-Children or MIS-C.https://www.thailandmedical.news/news/breaking-news-covid-19-warning-more-children-in-america-being-inflicted-with-deadly-mysterious-illness-linked-to-covid-19

In the United States of the 697,000 confirmed pediatric COVID-19 cases, most had comparatively mild illness and somewhere between 16 and 45 percent of children may not manifest any symptoms at all.
However about 1,027 American children went on to develop MIS-C.
Early signs included fever, rashes, abdominal pain, diarrhea, and vomiting and subsequent progression into severe inflammation in a matter of hours, often requiring intensive care, and were sometimes fatal.
Dr Alvaro Moreira, a physician scientist at the University of Texas in San Antonio published analysis of results from multiple scientific papers in EClinicalMedicine based on 662 cases of MIS-C. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30271-6/fulltext#%20
Interestingly MIS-C usually develops several weeks after the classic signs of the coronavirus appear in kids, such as cough, body aches, and runny nose. Studies have also revealed the condition can appear after an asymptomatic infection with the virus.
It is also scary as MIS-C can develop even when parents do not know their child has had COVID-19.https://www.thailandmedical.news/news/university-of-birmingham-researchers-warn-that-children-infected-with-covid-19-could-develop-kawasaki-like-syndrome-weeks-or-months-later-at-any-time-

What was found also was that even after clearing in the airways, the coronavirus may continue to replicate in the digestive system, particularly in children. It’s a discovery with implications far beyond rare pediatric cases.
Current nasal swabs and even fecal swabs are not able to detect growing colonies of the SARS-CoV-2 virus in the gastrointestinal track and this also has implications for the millions of recovered COVID-19 patients not just those affected by this particular strain.
Associate director of the Center for Gut Microbiota Research at the Chinese University of Hong Kong, Dr Siew Ng told Thailand medical News, “New research data show the SARS-CoV-2 coronavirus can linger in stool up to a month.”
Most MIS-C patients are older children.The median age of the afflicted is nine. They also carry higher levels of biomarkers ie proteins found in blood tests that predict inflammation levels, and they often experience severe abdominal pain.
In most cases physicians tend to be confuse the condition with appendicitis.
The multi-inflammatory syndrome is now also affecting certain adults  MIS-A) https://www.thailandmedical.news/news/breaking-covid-19-latest-u-s-cdc-warns-that-multisystem-inflammatory-syndrome-typically-found-in-children-now-manifesting-in-numerous-adults adn it is believed that the D839Y/N/E strain has evolved slightly to be able to do so.
The study team led by  Professor Dr Moshe Arditi, an expert on Kawasaki disease and a professor of pediatrics and biomedical sciences at Cedars-Sinai, a medical center in Los Angeles along with Professor Dr Ivet Bahar, distinguished professor of computational and systems biology at the University of Pittsburgh, found that SARS-CoV-2 has a unique feature in one part of its spikes. This spike fragment resembles the bacterial toxins known as super antigens ie proteins that generate excessive reaction from T cells, a vital member of the immune system. Other research shows that severe COVID-19 results from immune systems overreacting to coronavirus, causing cascades of excess inflammation that permanently damage many parts of the body.
The observed hyperinflammatory syndrome was reminiscent of toxic shock syndrome (TSS) observed in bacterial infections caused by two types of bacterial superantigens (SAgs) ie  Staphylococcus aureus and Streptococcus pyogenes that stimulate massive production of inflammatory cytokines and toxic shock.
Dr Arditi says the spike fragment may explain why MIS-C has the appearance of what happens during blood infections like sepsis or bacterial toxic shock syndrome.
Dr Bahar said, “We would expect that mutated spike region to elicit the same type of very strong response as other super antigens.”
Dr Bahar said that this revelation might bridge how and why the coronavirus causes other types of hyperinflammation when affected by other strains of the SARS-CoV-2.
Dr Arditi added, “We finally identified the segment in the viral spike segment that may induce all those immune responses” not only in MIS-C but possibly in adult COVID-19 cases.
Interestingly toxic shock has also long been associated with short- and long-term mental dysfunction, so Dr Bahar wonders if the super antigen quality of SARS-CoV-2’s spike might also explain the high percentage of neurologic symptoms seen in adult COVID-19 patients. One study reported nearly a third of hospitalized COVID-19 patients experienced altered cognitive function well after they were discharged. https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.51210
Importantly the distinguishing feature of both MIS-C and MIS-A from other COVID-19 infections are the gastrointestinal symptoms.
Dr Arditi says that, again, a clue might be found in the super-antigenic region of the virus’s spike.
Significantly because these symptoms can take weeks to manifest after an initial infection, nasal swabs and genetic tests for the virus the current methods for confirming the germ’s presence often come back negative. Some researchers now suspect the virus is still hiding in the body during MIS-C syndrome, possibly in the gastrointestinal tract.
Dr Siew Ng added, “Our gut carries the largest immune organ the intestine. Given the digestive tract is packed with a variety of immune cells. We should not ignore it.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714863/
Interestingly the SARS-CoV-2’s spike protein structurally looks similar to Staphylococcal enterotoxin B (SEB), which is made by bacteria and is one of the strongest gastrointestinal toxins known in medicine.
Dr Arditi added, “A very small amount of it in food will make you very sick, with very severe abdominal pain and a lot of vomiting,”
The coronavirus behind the original SARS epidemic in 2002-2003 also caused severe gastrointestinal disease.
A recent study in the medical journal Gut adds to this case, by showing the virus persists in the digestive tract long after it disappears from the nose, mouth, and lungs. Dr Ng, lead author of the paper, has even developed a coronavirus test for stool because she says it’s a better way to screen children and identify possible sources of silent transmission. https://gut.bmj.com/content/early/2020/07/19/gutjnl-2020-322294
Interestingly researchers also suspect that those infected with the D839Y/N/E but are obese or have diabetes or belong to certain ethnic groupings might be more severely affected by this new mutation. https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e2.htm
The study findings By Dr Ardit and Dr Bahar raise the exciting possibility that immunomodulatory therapeutic options used for TSS may also be effective for MIS-C, including intravenous immune globulin (IVIG) and steroids. Indeed, initial published and unpublished reports suggest that MIS-C patients respond well to IVIG with or without steroids. https://pubmed.ncbi.nlm.nih.gov/32386565/
IVIG contains antibodies that neutralize SEB (Staphylococcal enterotoxins B). Given structural similarities between SEB and the SARS-CoV-2 S protein SAg motif, there is potential for cross-reactivity of these immunoglobins, which may, in part, explain the response of MIS-C cases to IVIG.
Other FDA approved anti-inflammatory drugs tested in models of SEB TSS may also be effective, including CTLA4-Ig which can inhibit CD28 co-stimulation , and the mammalian target of rapamycin (mTOR) inhibitor rapamycin , which is already in use for COVID-19.
Dr Siew Ng also recommend that certain probiotics would be useful for patients suffering from MIS-C or MIS-A or even just ordinary COVID-19 but are having gastrointestinal problems.
Meanwhile, the international community has to spend more attention on the various emerging SARS-CoV-2 coronavirus mutations and variants.
Vaccines and antibody protocols will not be effective against some of these new emerging strains including in the case of this D839Y/N/E strain.
We will be proving more articles on the various emerging strains but in the meanwhile do read: https://www.thailandmedical.news/news/covid-19-latest-more-antibody-resistant-sars-cov-2-mutated-strains-emerging-and-increasing-in-circulation
For more COVID-19 News, keep on logging to Thailand Medical News.
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