You know it when you feel it: Scratchy throat, runny nose, and clogged sinuses. It’s the common cold and its relative absence may have been the only good thing about last year.
As it turns out, Covid-19 mitigation factors are good at preventing other viruses as well, like rhinovirus, the most frequent cause of the common cold. This has led some to speculate that this year, the common cold will be back with a vengeance — stronger and ready to make you miserable.
You might want to hope it does: Researchers from Yale University have found exposure to rhinovirus may actually protect against SARS-CoV-2 infection. Their results, published Tuesday in the Journal of Experimental Medicine, tell an elegantly simple (if counterintuitive) story about our body’s defense system.
Senior author Ellen Foxman, assistant professor of laboratory medicine and immunobiology at the Yale School of Medicine, tells Inverse that she and her colleagues wanted to know how quickly the body's antiviral defense turns on after a person is infected with the novel coronavirus.
“Some people can clear a virus really fast in those early days,” she explains. “Those are the people who avoid bad lung disease.”
“The people that don’t clear it in those early days, that’s when the virus can progress and become a really bad lung disease,” Foxman adds. “So we really wanted to see what happens in those early days.”
There was just one problem. “That’s a really hard thing to study in patients,” Foxman says, “because usually in those first few days, you don’t have symptoms.”
Fortunately, her hospital had been screening everyone for SARS-CoV-2 since March of 2020.
How the discovery was made — First, the study team wanted to see what the virus did in those early, pre-symptomatic days.
“Because we had so many patients, that just came up positive through routine screening [before they had symptoms], we could see what happens in their body with the virus and see what happens with their immune responses,” Foxman explains.
The researchers found that there was a delay before the body mounted any kind of immune response. In the absence of a defensive immunological response, the virus replicated exponentially.
“It [the virus] was doubling fast, like every six hours,” Foxman says.
After those few days, the immune response kicked. But it wasn’t the kind of immune response you’re probably familiar with.
The first line of defense — You’ve probably heard of antigens and T-cells: they’re part of the immune response that occurs when we get a vaccine. They can take the body days and weeks to produce.
The real first line of defense against respiratory viruses is in our airway.
The lining of our airway is covered with epithelial cells. As we go about our day, epithelial cells sit quietly alert, trying to sense any viruses that may be near.
When they detect a virus, they turn on signals that stimulate early defense molecules called interferons. Despite not being immune cells, interferons can still block the viral infection.
If only there was a way to stimulate that response earlier, the researchers thought, without letting the virus have that multi-day replication party.
How to kill a virus replication party — The researchers also grew human airway tissue in their lab and infected it with SARS-CoV-2. It mirrored the response they saw in the patients: exponential replication for the first few days and then those interferons kicked into gear.
“One virus blocks the replication of an unrelated virus.”
Previous research on rhinovirus and influenza suggested the interaction between those two viruses could ignite the response the study team was looking for. So the researchers grew the same human airway tissue and first infected with rhinovirus, the common cold. The epithelial cells sent their warning signals and interferons came ready to fight virus replication.
Then, the researchers introduced SARS-CoV-2. Because the interferons were already primed to fight the cold virus, there wasn’t the same multi-day coronavirus replication fest. The troops had been called to the battlefield before the enemy even put its pants on.
What it means — A virus priming an immune response for another virus is called viral interference Foxman says.
“One virus blocks the replication of an unrelated virus,” she says. “At first glance, it’s counterintuitive. But if the timing is right and the [SARS-CoV-2] viral load is low enough, it can happen.”
Those last two caveats are big ones:
- Viral load: If you have a cold and you’re exposed to a huge amount of coronavirus, interferons are going to be overwhelmed and will get past their defenses and deeper into the cell.
- Timing: As we’ve seen throughout the pandemic, an overactive immune response can cause more harm than good. By stimulating an interferon response after the first few days, a person’s immune system could go into overdrive and result in a cytokine storm.
What it means for the future — The good news is that with enough people vaccinated, the amount of SARS-CoV-2 floating around this fall will be pretty minimal. Hopefully, minimal enough where, if we catch that whopper of a cold we missed last year, our interferons will knock the coronavirus out without us ever being the wiser.
While it’s too soon to say how this could protect us with future coronaviruses or as vaccine immunity wanes, these findings could explain why rates of certain infections are lower when colds are more common. There’s possibly an “upper limit” when it comes to circulating respiratory viruses. Regardless, it’s better to be safe than sorry — and protect yourself from any viruses heading your way.
Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially with a doubling time of ~6hr and induced interferon stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection prior to SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2