How are some able to avoid COVID-19?
Research suggests many factors are likely at play
One of the lingering mysteries of the COVID-19 pandemic is why some people get infected without getting sick and others don’t get infected at all, despite exposure.
Beyond a few known risk factors, it’s mostly dumb luck that determines how someone will fare if they are exposed to the virus that causes COVID-19, a handful of researchers said.
But they’re still trying for more scientific answers by studying people who are intentionally exposed to the virus and those who escape its effects. People like Faith Paine.
Paine, 26, of London, volunteered for a “challenge trial” – meaning researchers dribbled the virus that causes COVID-19 up her nose, intending to get her sick.
For 17 days last year, she had to stay in a single room in London’s Royal Free Hospital, unable to leave, exercise or see anyone who wasn’t encased in a hazmat suit. The food was the worst part, she said, ordered ahead for her entire stay and more appropriate for an airplane ride than a regular diet.
Between all the poking and prodding, she was allowed to go to bed only after 11:30 p.m., and was awakened by 6:30 a.m. She felt awful the whole time, but she wasn’t sure whether it was because of the lack of sleep and mediocre food, or because she had COVID-19.
She didn’t.
Like half of the 36 U.K. residents paid about $6,500 to be willingly exposed to COVID-19, she never developed an infection and never shed virus.
Dr. Andrew Catchpole, who helped lead the research, said he didn’t expect everyone to get sick. He runs regular challenge trials for infections like the flu and always aims for about 50% to 70% to fall ill, to ensure he is giving enough, but not an unsafe amount of virus.
But it didn’t take much virus to give those 18 people COVID-19, and though data is still being analyzed, they have yet to identify a clear reason why the others didn’t catch it, or why some of those who did never reported significant symptoms.
“(That’s) the great unknown – the X factor that has yet to be discovered,” said Catchpole, chief scientific officer of Open Orphan, the company that ran the study.
Infection – or lack of one – mainly has to do with a chance combination of multiple factors, he and others said.
Many ingredients are in the mix, including amount of exposure, genetics, and immunity – “all factors which we are not aware of going on in our bodies and the environment which affect all these things,” Catchpole said.
For Paine, all the poking and prodding she went through – and the fact that she was chosen for the trial out of 26,000 people who raised their hands – was a happy reminder that she’s among the healthiest of humans.
“It’s quite nice to know everything is ticking along quite nicely,” she said, and it helped take away some of her fear of getting infected with COVID-19.
It never crossed her mind to quit the study early.
“If this is the two and a half weeks I have to give up to provide research to shorten the time we all have to live with this, that’s absolutely nothing,” she said.
For someone who is vaccinated, exposure likely plays a role in whether they get sick, said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai in New York.
That’s why “social distancing” from sick people and mask wearing reduces the likelihood of getting sick.
“It’s really just a question of not getting exposed in the right amount,” Krammer said.
With infectious diseases like HIV, malaria and the stomach bug, rare individuals have a genetic gift that allows them to avoid falling ill.
And just as studying those outliers can offer insights into those diseases and potentially lead to treatments, Dr. András Spaan, a microbiologist at The Rockefeller University in New York City, hopes to learn more about COVID-19 by studying people who don’t get it.
Spaan and his colleagues have already shown that genes can make COVID-19 worse. About 10% of patients with severe COVID-19 pneumonia share a genetic fluke, they found in a paper last fall.
No one knows how many people have such natural resistance to COVID-19.
“It might be super, super rare,” Spaan said.
When Spaan and his colleagues published their first paper on the subject back in the fall, they were inundated with 7,000 emails from people all over the world offering to participate in their research.
So far, he said, the group, which now includes 150 partners, has enrolled 700 volunteers, analyzing their DNA and experiences with COVID-19.
It’s unclear whether immunity to the virus that causes COVID-19 would translate to protection against other viral illnesses, such as the flu. Spaan thinks the luck is probably specific to COVID-19 and maybe even individual variants of the virus.
And very often, there’s a price to pay for genetic resistance to disease, which is why it tends to be biologically limited, he said. Genes that confer resistance to malaria, for example, also increase risk for sickle cell disease, a lethal and extremely painful blood disorder.
Still, Spaan said, it’s crucial to study these individuals.
“By studying how human genetics works against COVID, there may be evidence for therapeutics,” he said.
The human immune system has evolved a number of layers of protection, some of which have been around since our ancestors were single-celled organisms and others that arrived more recently, said Dr. Christopher Chiu, an infectious diseases physician and immunologist at Imperial College London.
One of these layers includes antibodies, which can recognize viruses, bind and neutralize them. Some of these antibodies can be found in the nose and begin attacking viruses like SARSCOV-2, which causes COVID-19, before they have a chance to enter the body.
“(If) the virus in the droplets or aerosols that you breath in are at relatively small amounts, having the antibody right there may well block infection completely,” said Chiu, who was chief investigator of the British challenge trial for COVID-19.
But it’s hard to measure levels of antibody in the nose, so it’s unclear whether someone has enough antibodies there to protect against infection.
The immune system’s T cells can also recognize virus-infected cells and clear them before the virus can grow too much or spread around the body. Again, these are tough to measure, Chiu said.