Two and a half years after the onset of the coronavirus pandemic, there is growing evidence that allergies that were once thought to put patients at risk for severe COVID-19 instead protect against the disease. Children with allergies are significantly less likely to become infected with COVID-19 for reasons that may be related to the virus, according to a long-term study funded by the National Institutes of Health published earlier this month.
“Historically, people with asthma and allergies have been susceptible to poor outcomes due to viral infections,” said Max Seybold, a pediatrician and genomics researcher at the National Jewish Health Hospital in Denver who led the study. “There was a real fear that this was a risk group.
Asthma, atopic dermatitis – the most common form of eczema – and food allergies are poorly grouped together as “allergic diseases”, in part because they tend to develop together. “It’s not like everyone with atopic dermatitis has food allergies [or] “There is asthma,” says Seybold.
The immune system mainly uses another type of inflammation, type 1, to fight viral infections. But for people with allergic disorders, a viral infection can cause both inflammatory alarm bells. “They have this kind of inflamed condition of their airways with two types of inflammation going on at the same time,” says Seybold, which could lead to a more serious illness.
Beginning in the spring of 2020, a team of researchers from numerous American institutes is recruiting children and teenagers from 12 different cities in the United States who have already participated in allergy or asthma research, as well as their key caregivers. Every two weeks between May 2020 and February 2021, 5,600 participants were tested for COVID, with additional tests for anyone who fell ill.
Thus, the study authors followed not only symptomatic or serious cases of COVID, which remain rare in children, but also asymptomatic. From these data, they calculated the risk of overall infection, along with the risks of serious illness. Estimating the overall infection rate is rare in COVID studies because collecting data on asymptomatic infections is so expensive. “It was a great undertaking to register a band and get samples from them regularly for a long time,” says Seybold.
In the survey, a quarter of all households and about 14 percent of all participants caught COVID.
[Related: CDC estimates 58 percent of Americans have been infected with COVID so far]
This infection rate suggests that COVID is more widespread than previously thought. “We found that 75 percent of infections in children are asymptomatic,” said Seybold. “If you compare our data with the CDC data for the same period of time, we are much more likely to get an infection in children. And these children had a high viral load, even when asymptomatic, suggesting they could spread the disease.
Allergic diseases affected the risk of COVID, but not in the way researchers would have expected. People with food allergies are 50 percent less likely to become infected with COVID, and transmission in the household is much lower when someone has had an allergy. Atopic dermatitis does not affect the risk. Nor is asthma – unless it is specifically asthma caused by allergic reactions.
Asked why, Seybold said, “The first thing I would say is, ‘We don’t know.’ ”
But the team has a guess. Proteins that cause type 2 inflammation can alter cell function, especially in the skin, airways and other membranes. Inflammation of type 2 can alter the expression of thousands of genes, says Seybold. “It’s a very powerful mechanism. If you affect many things, you can change some aspects of biology that affect something else, such as the risk of SARS-CoV-2.
In particular, previous work by Seibold and co-authors showed that people who had high levels of type 2 inflammation also had less protein called ACE2 in their airway cells. ACE2 appears to be the exact receptor to which SARS-CoV-2 attaches when it infects cells. This suggests that people with allergic disorders are less vulnerable at the cellular level to the virus.
“It’s not a reliable story,” Seybold said. “Why are asthmatics, for example, not protected?”
The answer to this question can be found in another study from 2019, which found that children with food allergies have much stronger signatures of type 2 inflammation than those with allergic skin diseases. “I think individuals with food allergies have the most extreme levels of type 2 inflammation and therefore the greatest effect on their receptor,” Seybold said before warning: “It’s all speculation.”
He summarizes the hypothesis as follows: Inflammation reduces ACE2 receptors in people with allergies. This in turn should reduce the risk of infection. But it has not been proven. “We have A to B and we have B to C, but it’s a little different than going from A to B to C,” says Seibold.
The team is currently studying participants’ cells by RNA sequencing. This may indicate whether participants known to be at low risk of COVID actually had severe inflammation and reduced ACE2 as predicted in other studies.
The results are consistent with other studies on allergies and SARS-CoV-2. A study published in March found that when lung cells were exposed to another key marker of inflammation type 2, they cleared the SARS-CoV-2 virus faster. And people with allergic diseases are about 25 percent less likely to be infected, according to an observational study in the United Kingdom published in late 2021.
Jasmine Akdis, editor of the magazine alergy and the director of the Swiss Institute for Allergy and Asthma Research, wrote in an email: “Although the publications are controversial, I think the existing allergy prevents the serious development of COVID.
However, Seibold does not want to draw broader conclusions about the link between infections and allergies. “I’m not sure there’s a strong conceptual link between this particular virus and the course of allergic diseases,” he said. “Potentially, two independent things happen – just things happen sometimes.”