New identification of genetic basis of COVID-19 susceptibility will aid treatment

Date:
June 6, 2020
Source:
European Society of Human Genetics
Summary:
Italian researchers have been able to identify the genetic basis of
susceptibility to Covid-19 infection, and also to the possibility
of contracting a more severe form of the disease. This has important
implications for treatment and drug development.



FULL STORY ==========================================================================
The clinical presentation of Covid-19 varies from patient to patient
and understanding individual genetic susceptibility to the disease is
therefore vital to prognosis, prevention, and the development of new treatments. For the first time, Italian scientists have been able to
identify the genetic and molecular basis of this susceptibility to
infection as well as to the possibility of contracting a more severe
form of the disease. The research will be presented to the 53rd annual conference of the European Society of Human Genetics, being held entirely on-line due to the Covid-19 pandemic, today [Saturday].


========================================================================== Professor Alessandra Renieri, Director of the Medical Genetics Unit
at the University Hospital of Siena, Italy, will describe her team's
GEN-COVID project to collect genomic samples from Covid patients across
the whole of Italy in order to try to identify the genetic bases of
the high level of clinical variability they showed. Using whole exome sequencing (WES) to study the first data from 130 Covid patients from
Siena and other Tuscan institutions, they were able to uncover a number
of common susceptibility genes that were linked to a favourable or
unfavourable outcome of infection. "We believe that variations in these
genes may determine disease progression," says Prof Renieri. "To our
knowledge, this is the first report on the results of WES in Covid-19." Searching for common genes in affected patients against a control group
did not give statistically significant results with the exception of
a few genes. So the researchers decided to treat each patient as an
independent case, following the example of autism spectrum disorder. "In
this way we were able to identify for each patient an average of three pathogenic (disease-causing) mutations involved in susceptibility to
Covid infection," says Prof Renieri. "This result was not unexpected,
since we already knew from studies of twins that Covid-19 has a strong
genetic basis." Although presentation of Covid is different in each individual, this does not rule out the possibility of the same treatment
being effective in many cases.

"The model we are proposing includes common genes and our results point to
some of them. For example, ACE2 remains one of the major targets. All our
Covid patients have an intact ACE2 protein, and the biological pathway involving this gene remains a major focus for drug development," says
Prof Renieri. ACE2 is an enzyme attached to the outer surface of several organs, including the lungs, that lowers blood pressure. It serves as
an entry point for some coronaviruses, including Covid-19.

These results will have significant implications for health and
healthcare policy. Understanding the genetic profile of patients may
allow the repurposing of existing medicines for specific therapeutic
approaches against Covid-19 as well as speeding the development of new antiviral drugs. Being able to identify patients susceptible to severe pneumonia and their responsiveness to specific drugs will allow rapid
public health treatment interventions. And future research will be aided,
too, by the development of a Covid Biobank accessible to academic and
industry partners.

The researchers will now analyze a further 2000 samples from other
Italian regions, specifically from 35 Italian Hospitals belonging to
the GEN-COVID project.

"Our data, although preliminary, are promising, and now we plan to
validate them in a wider population," says Prof Renieri. "Going beyond
our specific results, the outcome of our study underlines the need
for a new method to fully assess the basis of one of the more complex
genetic traits, with an environmental causation (the virus), but a high
rate of heritability. We need to develop new mathematical models using artificial intelligence in order to be able to understand the complexity
of this trait, which is derived from a combination of common and rare
genetic factors.

"We have developed this approach in collaboration with the Siena
Artificial Intelligence Lab, and now intend to compare it with classical genome-wide association studies in the context of the Covid-19 Host
Genetics Initiative, which brings together the human genetics community
to generate, share, and analyse data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes. As a research community,
we need to do everything we can to help public health interventions move forward at this time." Chair of the ESHG conference, Professor Joris
Veltman, Dean of the Biosciences Institute at Newcastle University,
Newcastle upon Tyne, UK, said: "We are very excited to have this
work on the genetics of COVID19 susceptibility presented as one of our late-breaking abstract talks at the ESHG. Our Italian colleagues present
the first insight into the role of genetic susceptibility influencing
the severity of the response to a COVID19 infection. It needs to be
expanded to encompass much larger populations, but it is impressive to
see the speed at which research on this virus has proceeded in just a
few months' time."

========================================================================== Story Source: Materials provided by
European_Society_of_Human_Genetics. Note: Content may be edited for
style and length.


==========================================================================


Link to news story: https://www.sciencedaily.com/releases/2020/06/200605182332.htm

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