July 13, 2021

Why researchers are investigating Covid-19 'outliers'

Daily Briefing

    Throughout the pandemic, many medical anomalies have occurred—including people who are 100 or more years old recovering from Covid-19. Now scientists are trying to understand whether certain genes or mutations affect susceptibility to Covid-19.

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    Researchers investigate the 'outliers'

    Over the course of the pandemic, there have been several unusual or "surprising" Covid-19 cases, the New York Times reports, often called "outliers." For instance, even as some people have tested positive for months at a time, others have remained uninfected despite sharing a home or even a bedroom with people who have fallen ill. And while some young, healthy, and vaccinated people have caught the virus, some far older, people—including one 114-year-old woman—have survived.

    Although not the norm, these medical anomalies have prompted scientists to research whether any genetic mutations provide protection for certain people against the Covid-19, the Times reports.

    Exploring genetic data as it relates to the susceptibility of chronic infections has been done before. For instance, when researchers investigated the cells of a man named Stephen Crohn—who appeared impervious to HIV infection—they discovered of a rare mutation that shielded him from infection. That discovery eventually inspired the development of an antiviral drug called maraviroc, a treatment for HIV infection that can lower the chance of HIV complications and improve quality of life. Similar patterns have followed with treatments for high cholesterol and other diseases, the Times reports.

    'I want to understand what makes someone survive.'

    Researchers hope that investigation into what accounts for Covid-19 outliers—both those who appear less susceptible and those who seem more vulnerable to infection—will help scientists develop potential new drugs, better identify promising drugs already in development, or even repurpose existing drugs that target certain specific genes.

    For instance, one study investigating two pairs of young brothers who had severe Covid-19 found genetic abnormalities involving the immune system molecule interferon. These findings, when paired with other research suggest that giving interferon to applicable patients might be an effective therapy.

    Looking forward, Mayana Zatz, director of the Human Genome Research Center at the University of São Paulo, is leading a study to understand how very old people—specifically those over 100 years old—recovered from Covid-19 unscathed.

    "To survive until 114 years old is not easy, and to survive after having had Covid-19 is even more difficult," Zatz said. "I want to understand what makes someone survive."

    In a similar, separate study in Nature, researchers assessed 50,000 patients across 25 countries and identified 13 genes that appear to play a role in infection susceptibility or illness severity. Some, including a gene involved in the response to respiratory infections, are unsurprising. Others, such as blood type, have no clear explanation. The study has since been expanded to include 125,000 Covid-19 patients.

    Hamdi Mbarek—research partnership director of the Qatar Genome Program, which participated in the research—said, "This is the biggest single genetic study in history of how people with slightly different DNA respond very differently to a virus. And because for the first time a study like this has involved genetic data from all parts of the world, that data will be more powerful in spotting the right genes to help develop treatments for severe COVID or long COVID."

    Separately, Michael Murray, a professor of genetics and director for clinical operations in the Center for Genomic Health at the Yale School of Medicine, who was not involved in the study, said that the study "lays the groundwork for better understanding of how to get at these things more quickly next time, so they can be applied at the beginning of a pandemic, rather than these insights coming at what we hope is the tail end." (Weintraub, USA Today, 7/9; Khamsi, New York Times, 7/12)

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