How sick
will the coronavirus make you? The answer may be in your genes
COVID-19,
caused by the new pandemic coronavirus, is strangely—and tragically—selective.
Only some infected people get sick, and although most of the critically ill are
elderly or have complicating problems such as heart disease, some killed by the
disease are previously healthy and even relatively young. Researchers are now
gearing up to scour the patients’ genomes for DNA variations that explain this
mystery. The findings could be used to identify those most at risk of serious
illness and those who might be protected, and they might also guide the search
for new treatments.
The
projects range from ongoing studies with DNA for many thousands of
participants, some now getting infected with the coronavirus, to new efforts
that are collecting DNA from COVID-19 patients in hard-hit places such as
Italy. The goal is to compare the DNA of people who have serious cases of
COVID-19 (which stands for coronavirus disease 2019)—but no underlying disease
like diabetes, heart or lung disease—with those with mild or no disease. “We
see huge differences in clinical outcomes and across countries. How much of
that is explained by genetic susceptibility is a very open question,” says
geneticist Andrea Ganna of the University of Helsinki’s Institute for Molecular
Medicine Finland (FIMM).
It’s
hard to predict what will pop out from these gene hunts, some researchers say.
But there are obvious suspects, such as the gene coding for the cell surface
protein angiotensin-converting enzyme 2 (ACE2), which the coronavirus uses to
enter airway cells. Variations in the ACE2
gene that alter the receptor could make it easier or harder for the virus to
get into cells, says immunologist Philip Murphy of the National Institute of
Allergy and Infectious Diseases, whose lab identified a relatively common
mutation in another human cell surface protein, CCR5, that makes some people
highly resistant to HIV.
Ganna
heads up a major effort to pool COVID-19 patients’ genetic data from around the
world. The idea “came quite spontaneously” about 2 weeks ago when “everyone was
sitting at their computers watching this crisis,” says Ganna, who is also
affiliated with the Broad Institute, a U.S. genomic powerhouse.
He
and FIMM Director Mark Daly quickly created a website for their project, the COVID-19
Host Genetics Initiative, and reached out to colleagues who run large biobank
studies that follow thousands of volunteers for years to look for links between
their DNA and health. At least a dozen biobanks, mostly in Europe and the
United States, have expressed interest in contributing COVID-19 data from
participants who agreed to this. Among them are FinnGen, which has DNA samples
and health data for 5% of the 5 million–person Finnish population, and the
50,000-participant biobank at the Icahn School of Medicine at Mount Sinai.
The
UK Biobank, one of world’s largest with DNA data for
500,000 participants, also plans to add COVID-19 health data from
participants to its data set, the project tweeted
this month. And the Icelandic company deCODE Genetics, which is helping
test much of the nation’s population to see who is infected with the new
coronavirus, has received government permission to add these data and any
subsequent COVID-19 symptoms to its database, which contains genome and health
data on half of Iceland’s 364,000 inhabitants, says its CEO Kári Stefánsson.
“We will do our best to contribute to figuring this out,” Stefánsson says.
Another
effort to identify protective or susceptibility DNA variants is the Personal Genome Project led by
Harvard University’s George Church, which recruits people willing to share
their full genome, tissue samples, and health data for research. Earlier this
month, it sent questionnaires to its thousands of participants, asking about
their COVID-19 status. More than 600 in the United States responded within 48
hours. “It seems that most people want to do their part,” says Church, whose
group isn’t yet part of Ganna’s collaboration.
Other
researchers working with Ganna’s initiative are recruiting COVID-19 patients
directly within hospitals for such genomics studies. Italian geneticist
Alessandra Renieri of the University of Siena expects at least 11 hospitals in
the nation to give ethics approval for her team to collect DNA samples from
willing patients. “It is my opinion that [host] genetic differences are a key
factor … for susceptibility to severe acute pneumonia,” Renieri says.
Pediatrics
researcher Jean-Laurent Casanova at the Rockefeller University, who specializes
in identifying rare genes that can make healthy young people susceptible to certain
serious diseases, is drawing on a network of pediatricians around the world to
look for the relatively few young people who develop COVID-19 serious enough to
get admitted to intensive care. “We study exclusively patients who were
previously healthy” and under 50, as their serious COVID-19 illness is more
likely to have a genetic basis, he explains.
In
addition to genetic variants of the ACE2 receptor, scientists want to see
whether differences in the human leukocyte antigen genes, which influence the immune
system’s response to viruses and bacteria, affect disease severity. And some
investigators want
to follow up a finding, which a Chinese team reported
in a preprint: that people with type O blood may be protected from the
virus. “We’re trying to figure out if those findings are robust,” says Stanford
University human geneticist Manuel Rivas, who is contributing to Ganna’s
initiative.
The
catastrophic spread of the coronavirus should soon increase the number of
COVID-19 patients available to these gene hunts. And that could speed findings.
Ganna expects the first susceptibility genes could be identified within a
couple of months.
With reporting by Elizabeth Pennisi.
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