It was Allison Guy had a good start to 2021. Her health was the best it had ever been. She loved her job and the people she worked with as a communications manager for a nonprofit organization. She could get up early in the morning to work on creative projects. Things looked “really, really good,” she says – until she got Covid-19.
Although the first infection was not fun, what followed was worse. Four weeks later, when Guy had recovered enough to go back full time, she woke up one day with an overwhelming fatigue that just never disappeared. It was accompanied by a loss of mental acuity, part of a series of sometimes difficult-to-identify symptoms, often referred to as Covid-19 “brain fog,” a general term for sluggish or vague thinking. “I spent most of 2021 making decisions like: Is it the day I take a shower or do I go up and microwave myself a frozen dinner?” Guy remembers. The high writing required for her job was ruled out. Living with these symptoms was, in her words, “hell on earth.”
Many of these difficult to define Covid-19 symptoms can continue over time – weeks, months, years. Now new research in the journal Cell sheds some light on the biological mechanisms of how Covid-19 affects the brain. Led by researchers Michelle Monje and Akiko Iwasaki of Stanford and Yale Universities, respectively, scientists found that in mice with mild Covid-19 infections, the virus disrupted the normal activity of several brain cell populations, leaving signs of inflammation. They believe that these findings may help explain some of the cognitive impairments experienced by Covid-19 survivors and provide potential avenues for therapies.
For the past 20 years, Monje, a neuro-oncologist, had been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms – also known as “chemo fog.” When Covid-19 emerged as a major immunoactivating virus, she was concerned about the potential for similar disorders. “Very quickly, when there were reports of cognitive impairment, it was clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, speed of information processing, dis-executive function – it’s really clinically similar to the ‘chemo fog’ that people experienced and that we had studied.”
In September 2020, Monje contacted Iwasaki, an immunologist. Her group had already established a mouse model of Covid-19, thanks to their Biosafety Level 3 approval to work with the virus. A mouse model is designed as a close stand-in for a human, and this experiment was intended to mimic the experience of a person with a mild Covid-19 infection. Using a viral vector, Iwasaki’s group introduced the human ACE2 receptor into cells in the mice’s trachea and lungs. This receptor is the entry point of the Covid-inducing virus, which allows it to bind to the cell. They then shot a bit of the virus up into the noses of the mice to cause infection, controlling the amount and delivery so that the virus was confined to the airways. For the mice, this infection disappeared within a week and they did not lose weight.
Together with the biosafety regulations and the challenges of cross-country cooperation, the security measures required by the pandemic created some interesting work constraints. Because most virus-related work had to be performed in Iwasaki’s laboratory, Yale researchers would take advantage of night transportation to fly samples across the country to Monje’s Stanford laboratory, where they could be analyzed. Sometimes they had to film experiments with a GoPro camera to make sure everyone could see the same thing. “We made it work,” says Monje.