Allison Guy was 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 conservation nonprofit. 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.
While the initial infection was not fun, what followed was worse. Four weeks later, when Guy recovered enough to go back to work full time, she woke up one day with an overwhelming tiredness that just never went away. This was accompanied by a loss of mental acuity, part of a series of symptoms that can sometimes be difficult to pin down which is 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 this the day I’m going to take a shower, or am I going to go up and microwave a frozen dinner for myself?” Guy remembers. The high-level writing required for her work was out of the question. To live with those symptoms was, in her words, “hell on earth.”
Many of these difficult-to-describe Covid-19 symptoms can persist over time — weeks, months, years. Now, new research in the journal Cell sheds light on the biological mechanisms of how Covid-19 affects the brain. Under the guidance of researchers Michelle Monje and Akiko Iwasaki, from Stanford and Yale universities, respectively, scientists determined that the virus in mice with mild Covid-19 infections disrupted the normal activity of several brain cell populations and left signs of inflammation. They believe that these findings may help explain some of the cognitive disruptions experienced by Covid-19 survivors and provide possible avenues for therapies.
For the past 20 years, Monje, a neuro-oncologist, has been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms – also known as “chemo mist.” When Covid-19 emerged as a major immune-activating virus, she was concerned about the possibility of similar disruption. “Very quickly, as reports of cognitive impairment began to come out, 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 really looks clinical just like the ‘chemo-mist’ that people have experienced and that we have studied.”
In September 2020, Monje reached out to Iwasaki, an immunologist. Her group has already established a mouse model of Covid-19, thanks to their Biosafety Level 3 clearance to work with the virus. A mouse model was designed as a close stop 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 trachea and lungs of mice. This receptor is the access point for the Covid-causing virus, which allows it to bind to the cell. Then they shot up some virus in the mice’s noses to cause infection, controlling the amount and delivery so that the virus was confined to the respiratory system. For the mice, this infection cleared up within one week, and they did not lose weight.
Together with biosafety regulations and the challenges of co-operation across the country, the security measures required by the pandemic have created interesting work constraints. Because most virus-related work had to be done in Iwasaki’s laboratory, the Yale scientists would benefit from overnight shipping to fly samples across the country to Monje’s Stanford laboratory where they could be analyzed. Sometimes they would have to film experiments with a GoPro camera to make sure everyone can see the same thing. “We made it work,” Monk says.