How an immunologist pivoted to tackle COVID-19 – Science

Science's COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation

Until this year, Akiko Iwasaki's lab had never handled so many tubes of human blood. We were mostly working with mouse models, says the Yale University immunologist, who speaks precisely and thoughtfully. We used to look at the data and contemplate it. Then COVID-19 struck, and such unhurried musings flew out the window. In a matter of weeks, Iwasaki overhauled her research to launch a slew of studies on how the new virus, SARS-CoV-2, takes its toll on patients. She and her nearly two dozen lab members know their discoveries could impact people falling sick right now. Every minute counts.

In the months since, she has produced a string of high-profile papers by redirecting her expertise in the immune system, honed in mice, to questions such as why men are more likely to get severely ill and how immune responses in hospitalized patients can help predict their prognosis. Now, she is turning her attention to long-haulers, people who suffer a bout with the virus and don't fully recover.

Iwasaki has had decades of practice adapting to new circumstances. As a child growing up in rural Japan, she dreamed of becoming a poet, turned off science by her physicist father's immersion in his profession. We'd go on vacation and he'd bring papers with him, she says, laughing. I thought, What kind of life is this? But when a high school teacher hooked her on math, she began to reconsider. Soon after, 9 months as an exchange student in Canada left her itching to escape the expectations for a woman in Japanese societymarry a nice man and have a family. Her mother, who worked at a local radio station, had endured jeers from co-workers for sticking with the job while raising three children. Knowing how much she stood up for always has stayed with me, Iwasaki says.

So she reimagined her future, embracing science and leaving Japan. She enrolled as an undergraduate at the University of Torontofalling hard for immunology her senior year thereand stayed on for graduate school. Twenty years ago she founded her lab at Yale, where she studies how the body responds to and combats viruses. Having to adapt to different situations throughout my life, she says, prepared me [for] a different virus.

The shift called for new science, new collaborations, and new skills. In February, Iwasaki's lab joined a universitywide testing effort for SARS-CoV-2 led by Albert Ko, Nathan Grubaugh, and Anne Wyllie at Yale's School of Public Health. Alice Lu-Culligan, a graduate student of Iwasaki's who had been studying the immune system during pregnancy in mice, recalls the scramble. Lab members scouted for supplies such as swabs and equipment. We were going around our floor, to the neighboring labs, seeing how many PCR [polymerase chain reaction] machines they had, Lu-Culligan says. It was full-on sprint mode, collaboration and chaos.

Having to adapt to different situations throughout my life prepared me [for] a different virus.

Akiko Iwasaki, Yale University

Iwasaki's lab began to help Grubaugh's group sequence viral genomes from early patients in Connecticut to map the spread there and across the United States. She also launched a separate study to examine patients' immune responses, recruiting 113 people with COVID-19 at Yale New Haven Hospital and redeploying skills in her lab to make the project happen. Postdoctoral fellow Carolina Lucas had been studying the mosquito-borne chikungunya virus, and her project was housed in a biosafety level 3 lab at the university, the kind used for hazardous pathogens. Akiko asked me to coordinate this, says Lucas, who quickly agreed.

Every few days, the team collected samples from the nose, throat, and blood of patients. There were all these weird immune responses being engaged, Iwasaki says. In severe cases, the immune system churned out a flood of cytokine proteins. Lucas, Iwasaki, and others found four immune signatures that appeared to correlate with later outcomes. That paper appeared in Nature in July.

Swiftly, the scientific questions mushroomed. In mid-March, the Yale hospital treated a woman with COVID-19 who was in her second trimester of pregnancy. The woman lost her fetusand a private tragedy became interwoven with urgent questions about whether the virus could infect the placenta and pose a danger to a pregnancy. A collaborator of Iwasaki's secured permission to collect the placenta, and late one night, Lu-Culligan retrieved it. Until that moment, the only placentas Lu-Culligan had seen belonged to mice. This is big and bloody, she says, and as she stared at it under a biosafety hood, I'm thinking, I don't know what I'm doing here.

In that case, the virus had indeed infected the placenta, and Lu-Culligan began to collaborate with Yale obstetricians to recruit women delivering at the hospital who were positive for the virus to study their placentas, too. That paper is nearing completion.

Meanwhile, Iwasaki began to investigate sex differences and found the male immune system is more likely to spark a harmful inflammatory response to the virus, whereas in women, T cells that fight it off are activated more robustly. These distinctions, she reported in an August paper in Nature, might help explain why men who are infected tend to fare worse than women.

Iwasaki's juggling act impresses her colleagues. She's made it seem so effortless, even though I know it's probably not effortless at all, says Angela Rasmussen, a virologist at Columbia University's Mailman School of Public Health. Iwasaki's husband, Ruslan Medzhitov, is also a well-known Yale immunologist (they discuss COVID-19 while walking their dog), and the pair has two daughters, ages 11 and 13. Iwasaki fears the pandemic is widening the gender gap in science as women face disproportionate pressure to support their children when schools are closed. Her husband drives their daughters to in-person school each morning, but with COVID-19 cases climbing, she wonders how much longer schools will be open.

Solutions to a COVID-19fueled gender gap in science are elusive, she says, other than to really have a different mindset about evaluating progress in science during this time. Iwasaki has long advocated for female and minority scientists on Twitter, where she has 80,000 followers. In one post, she minced no words in advising female scientists who worry about pregnancy torpedoing a job interview: If they don't welcome you with open arms and offer child care options, they don't deserve you.

Her advocacy goes beyond rhetoric. Lu-Culligan met Iwasaki at a luncheon for women in science at Yale, while struggling with bullying and harassment in another lab. Iwasaki said, We have to get you out of there, Lu-Culligan recalls. A few months later, the young scientist abandoned more than 2 years of graduate work to start over with Iwasakilater learning that she wasn't the first person her new mentor had rescued from a miserable experience elsewhere.

Some 8 months into the pandemic, lab life has settled downsomewhat. Iwasaki's latest passion is long-haulers who can't shake symptoms like fatigue and brain fog. Volunteers find her via word of mouth. The project faces hurdles, though: Iwasaki is hunting for a facility to draw blood from her volunteers, who are still symptomatic and potentially contagious. With many competing studies, such space is at a premium and she hasn't yet been able to secure any. She's also racing to apply for grants to fund the project.

We really want to get to the bottom of what's going on, she says impatiently. Until thenalong with so many other researchersshe'll be in overdrive.

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How an immunologist pivoted to tackle COVID-19 - Science