Are these golden hamsters the key to breaking long Kovid?

Do notEW YORK – In late 2020, Justin Frere, MD / Ph.D. The student dressed in white Tyvek to the head, took a clear pipette, and methodically entered the cells of 30 carefree, sedative hamsters, dripping 1,000 infected coronavirus particles into the nostrils of each of them.

Then he waited. Days for some. A full month for others.

The wait was very important. His goal, experts say, was to understand the group of symptoms that many Covid-19 patients suffer, weaken, and still misunderstand long after their initial infection, and perhaps one day become an important tool for effective treatment.


Frere and his adviser, Benjamin Tenover, a virologist at New York University, have long tried to create the first animal models for Covid. They announced the first results of the experiment this week Science Translational Medicine, mimic hamsters show some of the symptoms and molecular changes observed in humans and provide several valid explanations for the disease.

If further research is successful, these hamsters and several other groups of animals in other laboratories will allow scientists to study the basic biology of the mysterious disease, performing tests that humans could never perform. They may even allow academics and companies to allow screening before testing therapy in humans, an important step in building sterile therapeutic weapons.


“We desperately need new ways of learning to support the diagnosis and treatment of this condition,” said Harlan Krumholz, a Yeld cardiologist who has worked with Covid patients for a long time and is not involved in the work, in an email. “Any potential progress, especially in the development of animal models, is very welcome.”

TenOever is not alone. Yale Lab reported in December testing Two possible therapies in a mouse model. The following month, scientists at Stanford and Yel showed a model of a mouse that showed Covid and cancer patients with chronic brain fog. chemotherapy an experience. Stanley Perlman, a coronavirus expert at the University of Iowa, told STAT that he was working on his own model using a version of the coronavirus that could infect mice.

Each of these models has different advantages and disadvantages – for example, before Yale mice became infected with SARS-CoV-2, they had to be given some form of gene therapy, which could skew the results – but experts say the world eventually lost several animals to Covid. models are needed.

The reason is that long Kovid is not a condition, but an umbrella term for a few differences.

Yel immunologist Akiko Iwasaki, who helped create the Stanford-Yale model, said in an email: “We believe our model mimics some aspects of the human long Covid, but I can’t say that it perfectly mimics the long Covid.” “Long Covid is a very heterogeneous disease. Maybe there are four or five different drivers.” He said, “We need several models that reflect each.”

It’s important that researchers can recreate some of Covid’s symptoms in the lab for a long time to come, as researchers continue to debate what is causing the disease, said David Putrino, a Mountain Rehabilitation Specialist. Sinai’s health care system has long worked with patients with Covid.

“Saying ‘Animal Covid’s animal model’ really removes these claims, which are aimed at psychologizing Covid for a long time or telling people it’s just stress or anxiety,” Putrino, who contributed to Yale’s work, said.

At the beginning of the pandemic, tenOever used hamsters in its Biosafety Level-3 lab – first built to study the flu – to understand the course of the infection at the time and finally to test medications., At the request of the US government. However, the advent of mRNA vaccines by the end of 2020 has made these studies less urgent, while patient propaganda around Covid has long intensified, drawing the attention of researchers.

TenOever decided that its hamsters could set a good example for the long-term situation. They closely mimic acute infection in humans, probably because they have a similar type and level of ACE2 protein, and this protein uses it to locate cells.

“No matter where we look, no matter what we do with our hamsters, it’s always phenocopied in humans,” he said. “You can find something interesting in the hamsters and then take a biopsy sample of the person who matched them and it will always be transferred.”

Therefore, his team should not do what Pearlman and Iwasaki did and will not change the virus or mouse to the model. They can just infect hamsters and see what happens.

In addition to infecting 30 hamsters with Covid, Frere did not give anything to 30 hamsters and infected another 30 hamsters with the 2009 swine flu pandemic virus. Theoretically, twin governance allows researchers to determine what changes have taken place the wanted The infection and what changes were only for the coronavirus.

At first, some differences were obvious: the tested Covid hamsters, unlike those infected with the flu, lost their scent after three days. Researchers have demonstrated this by placing hamsters in a new cage with buried cocoa crumbs.

Influenza and non-infected hamsters dug directly into the medicine. Coronavirus hamsters “just wander, why am I here?” Said Free.

But there were many similarities. Both the coronavirus and the flu caused inflammation in the lungs and throughout the body, but the effects of the coronavirus were more severe.

But over time, that is likely to change. On the 31st, coronavirus-tested hamsters – whose symptoms may begin to be described as long Covid – may smell as easily as the other two groups. None of the hamsters had the virus. Inflammation in many parts of the body also passed, but some scars remained.

Except for one thing: the olfactory bulb, the potato-like cell mass behind the nose that transmits olfactory signals to the brain, remains inflamed a month later.

“This is a place where your SARS-CoV-2 response is different from your average response to infection,” tenOever said.

Although the olfactory bulb is not involved in cognitive functions, the inflammation in it can spread deeper into the brain. His team teamed up with a neurology lab to show that many of these hamsters’ neurons are still expressing genes involved in the body’s antiviral response.

They then examined the bodies of patients who became infected with Covid-19 and died after unrelated causes such as a car accident. Their brains showed a similar expression profile.

“They also had anti-virus protection, but there was no virus there,” tenOever said.

This has long shown several possible explanations for Covid, as well as possible therapies.

According to TenOver, there is a very strong inflammatory response to the virus because coronaviruses have a more stable and long-lasting genetic code than the flu. Eventually, even if the body clears it, the neurons can be pulled back permanently.

There may also be RNA debris or other types of viral debris, including particles such as zombies. damaged viral genomes – Although researchers can’t find it, it causes inflammation.

In both cases, you can try Paxlovid, a highly effective antiviral agent from Pfizer, either to clear the virus in newly infected patients and prevent long-term inflammation, or to clear potential viral residues in patients who have experienced Covid for a long time.

Ryan Langlois, an immunologist at the University of Minnesota, said: “It’s an obvious choice because it’s a very good drug.”

You can also try medications such as steroids that reduce inflammation or completely restore the immune response. Like the Iwasaki group, tenOever proposed a treatment that cleared the patient’s microglia, the ganglion cells of the brain.

The case has surprised some doctors who have been specialists for a long time. “This model needs to be carefully considered” Claire StevesThe Kings College Clinic in London said in an email.

However, there are significant limitations. First, the researchers used only the original strain of the coronavirus, but not the circulating variants now, but tenOever notes that the experiments began more than a year ago and that many long-term Covid patients were infected with the original virus. They also failed to mimic most of the symptoms observed in patients.

The closest of these was a test that put marbles in cells. Stress or anxious hamsters bury the marbles immediately. Indeed, the long Kovids have done so, but not sharply higher than those without the flu or infection.

Perlman, a coronavirus expert at the University of Iowa, said the hamsters did not have brain fog, heart disease or diabetes. “Nothing big time.”

Erkin said they acknowledged the restriction. In addition to testing the treatment, they hope to create models of pre-existing hamsters, such as those with heart disease or diabetes, to see if they can better fund the full range of Covid if they can provide funding. The current tests were only for young, healthy hamsters.

They also hope to test other hypotheses on the origin of Covid for a long time, including one hypothesis – the data is vague – suggesting that the virus could kill some nasal cells and alter the balance of the patient’s microbiome.

But all this requires funding. And hamsters in high-end warehouses are not cheap.

“These experiments are similar to the pop 50 grand,” tenOever said, referring to medical studies. “It’s not a huge amount.”

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