Since the pandemic started, BRI researchers have been hard at work trying to understand COVID-19’s biggest mysteries — like why people have such different responses to the virus and how it affects people with autoimmune disease. Now, a year later, they’ve made significant progress toward answering some of these questions.

“Our research includes investigating why the immune system is overactive and how we can harness it to fight disease," says BRI President Jane Buckner, MD. "Viruses and vaccines have always been part of that, so we had the tools in place to study COVID-19. And our clinical connection with Virginia Mason Franciscan Health gave us access to frontline clinicians and their patients, so we could collect patient samples that helped us move forward with these studies very quickly.”

Dr. Buckner and BRI Principal Investigator Adam Lacy-Hulbert, PhD, recently shared some of their findings and answers to pressing questions about COVID-19 at a Town Hall Seattle event. Here are key takeaways.

Why do some people with COVID-19 have no symptoms and others get seriously ill?

BRI researchers have been working to figure this out since the pandemic began. Working with clinicians at Virginia Mason, our team studied samples from people with varying severity of COVID-19 illness.

The research team found key differences between these people’s immune systems, based on specific characteristics called immune signatures.

“We collected samples and processed them the same day they were drawn,” Dr. Buckner says. “After the first three months, we looked at 60 patients and were able to identify some immune system characteristics that really highlighted differences between patients.”

This allowed them to find clear patterns: People with certain signatures had mild disease, while people with other signatures developed severe disease. And regardless of how sick the patient was on the day the sample was taken, their immune signature could predict if they would get a lot sicker or if they would be fine.

“If a doctor knew a patient had certain features, they could keep a closer eye on those individuals or make sure that the highest risk patients get to the hospital,” Dr. Buckner says. 

Can COVID-19 put the immune system into overdrive? How does that impact treatment for the virus?

Some COVID-19 patients experience an immune response called a cytokine storm. BRI’s Jessica Hamerman, PhD, likens this response to a broken fire alarm. The alarm keeps going off and more firefighters keep coming, even when the fire is out.

“The firefighters keep coming, spraying water and doing a lot of damage to your home if the alarm never stops,” she says. “Similarly, the cytokines keep calling in immune cells that make a lot of toxic molecules that can cause tissue damage and severe problems like pneumonia. The virus isn’t making these patients sick — it’s their immune system’s response to the virus.” 

Doctors have been using therapies to treat that overactive immune system response. But BRI scientists recently found out that while one part of the immune response is out of control, another part of the immune response — which plays a key role in fighting off viruses — is turned off in some patients.

“The patients have a virus infection yet their body is turning off the immune response to the virus,” Dr. Lacy-Hulbert says. “We think this may help explain why some people are getting severe disease. We’re continuing work in this area, trying to understand how this response gets turned off in severe COVID-19.”

These findings could lead to better, more personalized treatments for COVID-19: some patients may need one therapy to calm down the overactive response, and another to ramp up the virus-fighting response.

“We now realize that there may be a need to marry those drugs with others that will go in and actually help to boost this antiviral response and potentially help to remove that virus very early on in the infection,” Dr. Lacy-Hulbert says.

Why is COVID-19 worse in older people?

Dr. Buckner cited two potential reasons that older people become more seriously ill when infected with COVID-19. First, the immune system has a harder time ramping up and slowing down as people age.

“Over time, the immune system gets worse at starting and stopping,” Dr. Buckner says.

That means the immune system might not be able to mobilize and fight off invaders quickly enough. Or, it might keep fighting even though the invader is gone, causing an overreaction and making people sicker. In addition, as people age it is harder for them to make new immune memories. 

“You aren't able to make new memories as well as you get older,” Dr. Buckner says. “This becomes most important when we try to protect people with vaccines.”

BRI is also working to better understand changes in the immune system as we age, through the Sound Life Project. This multi-year study aims to better understand what happens as the immune system ages, including which changes are healthy and which lead to disease.

Should people with autoimmune diseases get the COVID-19 vaccine?

The initial COVID-19 vaccine studies did not include people with autoimmune diseases in the populations they studied. BRI researchers have teamed up with scientists at the University of Washington and are now studying the vaccine in people with autoimmune disease. This study could reveal key information about how autoimmune disease impacts the ability to respond to the vaccine, and how well the vaccine works for people taking immunosuppressive drugs.

“We recommend that patients with autoimmune diseases talk to their physicians about this, but medical guidelines are generally recommending that they get the vaccine because it's so important to be protected from this infection,” Dr. Buckner says. “So far, we aren't seeing any evidence that there are increased risks in the autoimmune population.”

Are COVID vaccines effective against variants?

Viruses (and all living things) can experience mutations, or small “typos” in their genetic code which lead to changes in their DNA. That’s how new virus variants arise — and scientists expected this to happen. News reports say some new variants are more contagious than previous strains of COVID-19.

That said, the data available so far suggests that the vaccines we have are largely effective against these new variants.

“The best thing we can do to limit the development of new variants is for us to get vaccinated and stop the virus from getting the chance to replicate and mutate,” Dr. Buckner says.

Can studying COVID-19 help us better understand autoimmune diseases?

BRI’s team is on a mission to improve diagnosis, prevention and treatments for people with autoimmune diseases. Our work studying COVID-19 can help our autoimmune disease research in a number of ways.

"In my lab, it's been an opportunity to develop new tools that have helped us understand COVID-19,” Dr. Lacy-Hulbert says. “Now we can use those to study autoimmune disease, and we can understand things about the immune system that we weren't able to measure before."

This research has also launched countless new questions: Can understanding the overactive immune response in some COVID-19 patients tell us something about what happens in people who get autoimmunity? Can we learn more about how viruses might trigger autoimmunity?

“We’ve come so far in the past year,” Dr. Buckner says. “We've learned more about how viruses disrupt the immune response, how vaccines cause immunity. We've learned about new defense pathways against viral infection. And those findings can help us make progress against autoimmune disease, which is what really drives us at the Benaroya Research Institute.”