Hunt Is on for Genetic Clues to Why Coronavirus Impact Varies - The Wall Street Journal

A Covid-19 patient is checked in at Javits New York Medical Station in New York... — A Covid-19 patient is checked in at Javits New York Medical Station in New York on April 5.
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Amy Dockser Marcus

The Wall Street Journal

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Amy.Marcus@wsj.com

April 7, 2020 7:43 am ET

Scientists around the world are pooling their knowledge and resources to determine whether gene variations make people more susceptible to serious Covid-19 infection, hoping to learn why some patients’ coronavirus symptoms are quite mild while others’ are severe.

Those studying the outbreak say one of the most perplexing questions is why some young and middle-aged people who have no underlying disorders, and appear to be otherwise healthy, have required serious medical intervention or died after being infected.

“Genetics is often a numbers game in order to find associations,” said Adam Auton, principal scientist at consumer DNA testing company 23andMe, which on Monday announced it had launched such a study. “The more people that are involved, the better.”

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Prior research indicates that some gene variants can render people a higher risk for infections, while others confer protection against them. Researchers discovered more than 20 years ago, for example, that a CCR5 gene variant protects against infection with HIV, the virus that causes AIDS.

Jean-Laurent Casanova of The Rockefeller University in New York said his lab has discovered gene variations that make some people more susceptible to severe influenza, fungal disease and tuberculosis.

Dr. Casanova is working with collaborators world-wide to enroll patients who were previously healthy, under the age of 50 and have no underlying medical conditions yet ended up in ICUs with what he called “life-threatening, unexplained Covid.” He said the number of such patients is likely to be small, perhaps 1% of severe cases, and that the collaborating researchers hope to recruit 1,000 to 2,000 people.

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Discovering any gene variant underlying severe Covid-19 infections would have many potential uses, Dr. Casanova said: It could pave the way for prevention or treatment of the disease, make it possible to apply existing drugs that help address a genetic deficiency, or simply inform future genetic counseling of family members.

There is hope that findings may also apply to elderly patients or those with other existing health conditions but might have been more difficult to tease apart, he said.

Mark Daly, director of the Institute for Molecular Medicine Finland in Helsinki and member of the Broad Institute of the Massachusetts Institute of Technology and Harvard University, is one of a group of geneticists around the world involved in the recently launched Covid-19 Host Genomics Initiative, which is also on the hunt for genes that might help explain why some fare better than others.

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There are already groups with existing genetic databases that are doing their own studies and have agreed to share their analyses and data with the consortium, Dr. Daly said. Some facilities have agreed to do genome sequencing for investigators who have access to patient samples but don’t have the resources for analysis, he said, and more than 80 institutions have agreed to participate.

“Genes contribute to variation in almost every human characteristic to some extent,” said Dr. Daly. Age and underlying health conditions don’t fully explain why some people have relatively mild illness or show few symptoms while others have life-threatening responses. “We are going to need to pool all the data to make genuine progress.”

The 23andMe project organizers said they believe they can move quickly because 80% of the company’s 10 million-plus customers who sent in DNA samples have given permission for them to be used for research.

The company is asking customers to participate in the study, which will be conducted monthly using online surveys. It hopes to enroll people who have tested positive and negative for the virus as well as their family members.

Dr. Auton said the surveys will try to capture data on a range of experiences with Covid-19, including whether patients had been tested and how symptoms changed over the course of the illness.

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Write to Amy Dockser Marcus at amy.marcus@wsj.com

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