look to the extremes Beating Covid and other future viruses may lie in examining the people who are highly resistant, and also the highly susceptible, to find the genes that matter most.
Even as the project began, Zhang already had a culprit in mind. In the 1960s, scientists discovered that our cells have an inbuilt alarm system to alert the rest of the body when it's being attacked by a new virus. "When a virus enters a cell, the infected cell makes proteins called 'type one interferons', which it releases outside the cell," explains Zhang. "All the surrounding cells receive that signal, and they devote everything to preparing to fight that virus. If the infection is serious, then cells will make enough type one interferon that it's released into the bloodstream, and so the entire body knows that it's under attack."
But sometimes genetic flaws mean that this system malfunctions. In 2015, Rockefeller scientists identified mutations in young, otherwise healthy people which led to them developing severe pneumonia from influenza. The mutations meant that the interferon response was non-existent. "If the alarm is silenced, then the virus can spread and proliferate much faster within the body," says Zhang.
It appears this also plays a role in making some people unexpectedly vulnerable to Covid-19. A series of scientific papers published in September 2020 compared 987 outliers – Covid-19 patients who developed severe pneumonia who were either younger than 50, or older than 50 and without any co-morbidities – to asymptomatic patients. Around 3.5% had a major gene mutation which made it impossible for them to generate an interferon response.
