Allison Guy was she’s off to a great start in 2021. Her health has been the best it’s ever been. She loved her job and the people she worked with as a communications manager for a non-profit conservation organization. She could get up early in the morning to work on creative projects. Things were looking “really, really good”, she says – until she got Covid-19.
While the initial infection wasn’t fun, what followed was even worse. Four weeks later, when Guy had recovered enough to return to work full-time, she woke up one day with an overwhelming fatigue that never went away. It was accompanied by a loss of mental acuity, part of a cluster of sometimes hard-to-define symptoms often referred to as Covid-19 “brain fog”, a general term for sluggish or unclear thinking. “I spent most of 2021 making decisions like, ‘Is this the day I take a shower, or do I go upstairs and microwave a frozen dinner for myself?'” Guy recalls. The high-level writing required for her job was out of the question. Life with these symptoms was, in her words, “hell on earth.”
Many of these hard-to-define symptoms of Covid-19 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. Led by researchers Michelle Monje and Akiko Iwasaki from Stanford and Yale universities, the scientists found that in mice with a mild infection of Covid-19, the virus disrupted the normal activity of several populations of brain cells and left behind signs of inflammation. They believe 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, has been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms — similarly known as “chemo fog.” When Covid-19 emerged as a major immune-activating virus, she became concerned about the potential for a similar disorder. “Very quickly, when reports of cognitive impairment started coming out, it became clear that it was a very similar syndrome,” she says. “The same symptoms of impaired attention, memory, processing speed, dys-executive function — it really looks clinically just like the ‘chemo fog’ that people have experienced and that we’ve studied.”
In September 2020, Monje contacted 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. The mouse model was designed as a close substitute for humans, 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 entry point for the virus that causes Covid, allowing it to bind to the cell. They then shot a small amount of virus into the mice’s nose to induce infection, controlling the amount and delivery so that the virus was confined to the respiratory system. In mice, this infection cleared up within a week and they did not lose weight.
Along with biosecurity regulations and the challenges of intergovernmental cooperation, the safety precautions required by the pandemic have created interesting operational constraints. Since most of the virus work had to be done in Iwasaki’s lab, Yale scientists would use overnight shipping to ship samples across the country to Monje’s lab at Stanford where they could be analyzed. Sometimes they would have to film the experiments with a GoPro camera to make sure everyone could see the same thing. “We succeeded,” says Monje.
