Yale researchers have conducted an experiment on “humanized mice” to try and get insight into why some people experience more severe symptoms than others when contracting the COVID-19 virus. The study found a link between the body’s inflammatory response to infection.
Researchers also found two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID-19. The study was conducted on mice who were “engineered to possess human-like immune systems” states the Yale report published in the journal Nature Biotechnology. Researchers posed the question, “why do 80 to 90% of people infected with COVID-19 experience only mild cases while 10 to 20% face more severe or life-threatening symptoms?”
Thus far comparing the virus in humans and laboratory animals “made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID-19.” But, the unique use of rodents with humanized immune systems offered this finding to researchers:
“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanized mice get sick and just don’t get better. Their whole immune system is on fire.”
The research team — which was led by first author Esen Sefik, a Howard Hughes Medical Institute (HHMI) Fellow at the Damon Runyon Cancer Research Foundation — introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanized mice and then followed the course of the disease.
They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies provided by Michel Nussenzweig, an immunologist at Rockefeller University and, like Flavell, an HHMI investigator. These antibodies, which specifically target the virus, were effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections, they found.
Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, it helped clear infection during later stages of disease by suppressing the inflammatory response that had begun damaging organs.
“Early in the course of the disease, a strong immune response is crucial for survival,” Sefik said. “Later in the disease, it can be fatal.”
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Fauci’s NIH gives another $3.5 million to EcoHealth despite dangerous past of coronavirus research
Just before he retires, Dr. Anthony Fauci has pushed through a new five-year grant for EcoHealth. EcoHealth Alliance, is the U.S. nonprofit that Fauci and the National Institute of Health’s funds, “to conduct dangerous coronavirus research in partnership with China’s Wuhan Institute of Virology prior to the global Covid-19 pandemic” reports National Review.
Over the next five years, the troublesome EcoHealth will receive over $3.25 million; their first check comes this year for $653,392. The grant is one of four concurrent NIH grants that EcoHealth has; three of the grants were awarded after the start of the Covid-19 pandemic.
The description of the grant on the NIH RePORTER website is to analyze “the potential for future bat coronavirus emergence in Myanmar, Laos, and Vietnam.”
“This is high-risk research that involves going into remote, often inaccessible areas, and sampling bats and bat excreta, and then returning those samples to laboratories in population centers where they attempt to isolate the virus … and then seek to characterize the threat level posed by the virus,” said Richard Ebright, a biosafety expert and professor of chemistry and chemical biology at Rutgers University. “This is one of the kinds of research that may have been directly responsible for the current pandemic.”
The term gain-of-function research has become very controversial since the global Covid-19 pandemic, and National Review reports on the subject:
This newest EcoHealth project wouldn’t qualify as gain-of-function research, Ebright said. Gain-of-function research involves extracting viruses from animals and engineering them in a lab to make them more transmissible or dangerous to humans. But Ebright said two of EcoHealth’s grants do involve gain-of-function research and enhanced potential pandemic research on coronaviruses. And even if the current description of the new project doesn’t involve gain-of-function research, that doesn’t mean it couldn’t later.
From securing funding to completing the research, it is a six-year process, Ebright said, and the project is bound to change over those six years. “If researchers robotically followed what they proposed six years ago, they would not be taking into account developments in their own labs and in the field at any point along the way,” he said. “You have to have this flexibility. That also means you need oversight to make sure the flexibility isn’t going into forbidden areas.”
Going into forbidden areas is exactly how EcoHealth and its president, Peter Daszak, previously got into trouble. Starting in 2014, the U.S. government temporarily paused funding for gain-of-function research due to concerns over biosafety and biosecurity. When some of EcoHealth’s research – involving infecting genetically-engineered mice with hybrid viruses – seemed to cross that line, NIAID staff and EcoHealth leaders crafted work-around guidelines to allow the nonprofit to continue its work.
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