Alison Guy is 2021 is off to a good start. Her health is the best ever. She loves her job and the people she works with as a communications manager for a conservation nonprofit. She can get up early to work on creative projects. She said things looked “very, very good” – until she contracted Covid-19.
While the initial infection wasn’t fun, the subsequent ones were worse. Four weeks later, when Guy had recovered enough to resume full-time work, she woke up one day with extreme fatigue that never went away. It is accompanied by a loss of mental acuity, part of a sometimes difficult to pinpoint set of symptoms commonly referred to as Covid-19 “brain fog,” an umbrella term for slowed or blurred thinking. “I spent most of 2021 making decisions like: Is this my shower day, or am I going to go up and microwave myself a freezer dinner?” Guy recalls. The high level of writing her work requires is impossible. Living with these symptoms was, in her words, “hell on earth.”
Many of these hard-to-define Covid-19 symptoms can persist for weeks, months, years.Now, new research from the journal cell The biology of how Covid-19 affects the brain is being elucidated. Led by researchers Michelle Monje and Akiko Iwasaki from Stanford University and Yale University, respectively, scientists determined that in mice with mild Covid-19 infection, the virus disrupted the normal activity of several populations of brain cells and left signs of inflammation. They believe the findings may help explain some of the cognitive impairments experienced by Covid-19 survivors and offer potential avenues for treatment.
For the past 20 years, neuro-oncologist Monje has been trying to understand the neurobiology behind chemotherapy-induced cognitive symptoms, also known as “chemo fog.” When Covid-19 becomes a major immune-activating virus, she worries about the potential for similar disruption. “Soon, as reports of cognitive impairment started to emerge, it became clear that it was a very similar syndrome,” she said. “The same symptoms of impaired concentration, memory, speed of information processing, executive function — it looks clinically like the ‘chemo fog’ that people experience and we’ve been studying.”
In September 2020, Monje contacted immunologist Iwasaki. Her group has created mouse models of Covid-19, which, thanks to their Biosafety Level 3 clearance, can work with the virus. The mouse model was designed as a close surrogate for humans, and the experiment was designed to mimic the experience of people with mild Covid-19 infection. Iwasaki’s team used a viral vector to introduce 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 cells. They then injected a little of the virus into the nose of the mice to cause infection, controlling the amount and transmission so that the virus was confined to the respiratory system. For the mice, the infection went away within a week, and they didn’t lose weight.
Combined with the challenges of biosecurity regulations and cross-border collaboration, the safety precautions required by the pandemic have created some interesting working constraints. Since most virus-related work must be done at the lab in Iwasaki, Yale scientists will use overnight shipping to airlift samples from across the country to the Stanford lab in Monje, where they will be analyzed. Sometimes they need to film experiments with a GoPro camera to make sure everyone sees the same thing. “We made it work,” Monje said.
