Are these golden hamsters a key to cracking long Covid?

New York — In late 2020, Justin Frere, a wiry M.D./Ph.D. student dressed in head-to-toe white Tyvek, picked up a clear pipette, methodically reached into the cages of 30 unsuspecting, sedated hamsters and drip-dropped 1,000 infectious coronavirus particles down each of their nostrils.

Then, he waited. Days for some. A whole month for others.

The waiting was essential. His goal was to make a tool experts say will be critical to understanding and perhaps one day effectively treating long Covid, the debilitating and still scarcely understood constellation of symptoms that afflict many Covid-19 patients long after their initial infection has passed. 

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Frere and his adviser, New York University virologist Benjamin tenOever, were trying to make one of the first animal models for long Covid. They reported the first results from the experiment this week in Science Translational Medicine, showing the hamsters mimic some symptoms and molecular changes observed in humans and pointing to several plausible explanations for the disease.

If further research bears out the results, these hamsters and several other groups of animals at other labs could allow scientists to probe the basic biology of the mysterious disease, performing the kinds of analyses that you could never do in humans. They may even allow academics and companies to screen therapies before testing them on humans, a crucial step in building up what remains a barren therapeutic armamentarium.

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“We are in dire need of new pathways to knowledge that can support diagnostics and therapeutics for this condition,” Harlan Krumholz, a Yale cardiologist who has been working with long Covid patients and was not involved with the work, said in an email.  “Any potential advance, especially the development of an animal model, is very welcome.”

TenOever isn’t alone. In December, a Yale lab reported testing two possible therapies on one mouse model. The next month, scientists at Stanford and Yale displayed a mouse model that shows the brain fog both long Covid and cancer patients on chemotherapy experience. Stanley Perlman, a coronavirus expert at the University of Iowa, told STAT he is working on his own model, using a version of the coronavirus adapted to infect mice. 

Each of these models has different pros and cons — the Yale mice, for example, first had to be given a kind of gene therapy before they were infected with SARS-CoV-2, which could skew results — but experts say the world will ultimately need multiple animal models for long Covid. 

That’s because long Covid is likely not one condition, but an umbrella term for multiple distinct ones.

“We believe that our model recapitulates some aspects of human long Covid, but I would not say it models long Covid perfectly,” Akiko Iwasaki, a Yale immunologist who helped create the Stanford-Yale model, said in an email. “Long Covid is a very heterogeneous disease. There are likely four or five distinct drivers.” And, she said, “We need multiple models that…