Why Are Some People Seemingly Immune to Covid-19? Scientists May Now Have an Answer

Researchers tracked the immune responses of 16 people intentionally exposed to SARS-CoV-2 and pinpointed a gene that seems to help resist the virus before it can take hold

A female doctor in a mask and visor gives a nasal swab to a male patient.
A new study sheds light on the timeline of the human immune response when confronted with SARS-CoV-2 and other infectious diseases. Ergin Yalcin via Getty Images

More than four years after Covid-19 was declared a pandemic that has since totaled more than 775 million cumulative cases worldwide, scientists are shedding light on the specific immune responses that have made some people seemingly resistant to catching the virus.

New research emerging from the United Kingdom, conducted as part of the Covid-19 Human Challenge Study and the Human Cell Atlas project, has found that a combination of robust nasal cell defense and high activity of a particular gene work together to ward off the virus in some individuals before it can take hold.

The research, published last week in the journal Nature, provides clarity on the timeline of the human body’s immune response to SARS-CoV-2 and other infectious diseases.

“These findings shed new light on the crucial early events that either allow the virus to take hold or rapidly clear it before symptoms develop,” Marko Nikolić, the study’s senior author and an honorary consultant in respiratory medicine at University College London (UCL), says in a statement. “We now have a much greater understanding of the full range of immune responses, which could provide a basis for developing potential treatments and vaccines that mimic these natural protective responses.”

Conducted in 2021, the study began with the researchers spraying a low dosage of the original SARS-CoV-2 variant up the noses of 36 healthy adult volunteers who were both unvaccinated and had never had the virus before.

From this group, researchers collected 16 volunteers’ nasal and blood samples on multiple occasions—before exposure and several times in the following 28 days—to track the spread of the virus and the participants’ immune responses. Sequencing these samples, the team produced a data set containing more than 600,000 individual cells and their behaviors before, during and after exposure.

The volunteers’ responses fell into three distinct categories. Six people became ill and displayed symptoms; three people briefly tested positive for Covid-19 but were asymptomatic, known as a transient infection; and seven people consistently tested negative and displayed no symptoms, but built up an immune response to the virus—what the team called an abortive infection.

In these latter two groups, participants showed high baseline activity of a gene called HLA-DQA2, which helps to efficiently alert the immune system to potential threats.

“These cells will take a little bit of the virus and show it to immune cells and say: ‘This is foreign: You need to go and sort it out,’” Kaylee Worlock, a molecular biologist and post-doctoral research fellow at UCL, tells the Guardian’s Hannah Devlin.

Another common trait among people in the two latter groups related to the production of interferon, or proteins that help bolster the body’s immune system. For these volunteers, interferon was produced in the blood before it appeared in the upper nasal region.

The people with transient and abortive responses developed a quick immune response—built up within about one day—inside their noses. Meanwhile, those who tested positive for Covid-19 took an average of five days to build up a nasal immune response.

Notably, the participants were not immune to getting Covid-19—some later caught the virus in the community, after the research concluded. And now, several other variants of SARS-CoV-2 are circulating—not just the original variant that was tested. But scientists say the research offers important clues to immune resistance.

“This study serves as a unique resource of previously uninfected SARS-CoV-2 participants due to its carefully controlled design and real understanding of ‘time zero’ for when the infection took place in order to measure the immune responses that follow,” José Ordovas-Montanes, an immunologist at the Harvard Stem Cell Institute who was not involved in the research, tells New Scientist’s Sonali Roy.

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