Six weeks ago, with little fanfare, a network of geneticists launched an obscure but potentially game-changing initiative. Their aim: to learn why people with particular DNA profiles end up dying from the coronavirus—or completely avoiding its effects. Ultimately, they want to devise ways for scientists to cook up new therapies that might alter how our nanosize genes operate as a way of reversing or accelerating the pathogen’s progress. Called the COVID-19 Host Genetics Initiative, the project now involves close to 700 scientists and researchers, worldwide, who are busily comparing DNA data from pandemic victims to literally millions of existing DNA profiles of millions of people.
To appreciate how our genes might be impacted by the onslaught of COVID-19, imagine this: that a tiny, invisible bug is hovering over the surface of a cell inside your body—say a lung cell. You don’t know it yet, but you’ve just been infected with SARS-Cov-2. Maybe it came from that jogger who whizzed past you on the sidewalk, or that tabletop you touched before rubbing your eyes. Whatever its source, there it is, circulating inside you: a fuzzy, sphere-shaped pathogen that’s less than 1/1000 the width of a human hair. Prickly, with spikes on its outside, it’s searching for a place to plug into and enter your cell. It’s a little like a key and a lock, where the key (the virus) wants to slip into the keyhole (a receptor on the cell) and then release a payload that will be up to no good.
Except that, in some people, the virus-key doesn’t fit the lock and is blocked from entering the cell. In others, it slips right in, leading to illness and sometimes to rapid deterioration and even death. One potential difference—say geneticists who are working day and night to better understand how SARS-Cov-2 invades and attacks our cells—might be because your DNA code differs from mine. Yours might inherently spurn the virus at the cellular level; mine might make me more susceptible.
So what determines who gets dangerously sick? “We know that people who are older and have underlying diseases like diabetes and heart disease are at higher risk for having a bad response to COVID-19,” explained Mark Daly, a 52-year-old geneticist and the director of the Institute for Molecular Medicine in Helsinki, Finland. Other factors include higher risk “biases” that involve ethnicity, class, vocation, geographic location, and the medical resources available at the time of treatment. And yet, according to Daly, “this doesn’t explain why relatively healthy people, including young people, are sometimes having severe and life-threatening reactions” such as very high fevers, pneumonia, and difficulty with breathing that requires oxygen and sometimes a ventilator. “Most likely this has something to do with differences in their genes.”
Daly should know. With his Paul Revere–like ponytail, circular hippie glasses, and lean, determined face, he’s a pioneer of modern genetics who was a key player during and after the Human Genome Project, the huge international effort in the 1990s and early 2000s that sequenced the first-ever human genome. And as the pandemic has been raging, Daly, a physicist, decided to help spearhead a remarkable “hive-mind” effort: the COVID-19 Host Genetics Initiative.
THE RACE FOR THE CODE
The project was announced on March 16 in a tweet posted by Daly’s cohort Andrea Ganna: “Goal: aggregate genetic and clinical information on individuals affected by COVID-19.” The response was immediate. Within days, scientists from over 150 organizations in more than 30 countries on six continents agreed to join. That’s the ideal use of “the hive mind”: a conglomeration of big brains and, in this case, their disparate data sources, to solve one huge problem. Participants have come not only from Harvard and MIT (institutions with which Daly has ongoing affiliations) and the usual institutional suspects in North America, Europe, and the wealthier Asian countries, but also from the Qatar Genome Program, Vietnam’s SARS-Cov-2 Susceptibility Program, and CLHORAZ—based in Burkina Faso.
The underlying quest: to identify which specific genes in a person’s 20,000-plus gene sequence of DNA actually impact our response to COVID-19. By cracking the inner DNA code behind severe reactions to the virus, scientists might then be able to design better treatments and even vaccines that might modify genetically induced responses to the coronavirus. Daly and his colleagues also want to concoct a DNA test that might reliably predict if a healthy person has a genetic predisposition to becoming compromised.
“This [initiative] is happening really fast,” said Ganna, who is a group leader at the Institute for Molecular Medicine—he comes from Northern Italy, where COVID-19 has been particularly harsh. “It also is completely inclusive and open. For instance, I’m helping a researcher organize a collection [of human DNA] in Kenya.” Diverse DNA is key: For too many years, genetic research has favored Caucasians, without a broader picture of how the virus affects everyone.
Each partner in the consortium has agreed to assemble applicable DNA sequencing data from COVID-19 victims who, in the past few weeks, have been tested and treated in hospitals and clinics in their regions. Then, in a process called “mining,” the geneticists compare each patient’s DNA to corresponding data collected over the past few years from data sets in lab after lab and country after country, sometimes drawing from the DNA samples of hundreds of thousands of people in a given area.