Why our immune system might be better at fighting COVID-19 than we think

You may have seen the headlines this week implying that antibodies the immune system creates to fight off the coronavirus decline rapidly after infection, jeopardizing the hope for long-term immunity from the virus. 

But the issue is both more complicated than it may seem and more hopeful. 

The preprint study, which has not undergone peer review, found the number of people with detectable antibodies in their blood in England fell from six per cent of the population at the end of June to just 4.4 per cent by mid-September.

The researchers concluded there was “decreasing population immunity” and “increasing risk of reinfection” and that the community study of 365,000 patients clearly showed detectable antibodies were in decline.

But while the study and its discouraging conclusion made headlines around the world, experts say there’s a lot more to consider before we can definitively say coronavirus antibodies don’t last long enough to protect us. 

Drop in antibodies after infection is expected

One key factor to keep in mind is that it’s not uncommon for immunity to drop after an infection, said Alyson Kelvin, an assistant professor at Dalhousie University and virologist at the Canadian Center for Vaccinology evaluating Canadian vaccines with the VIDO-InterVac lab in Saskatoon.

“Simply showing that antibodies decline after an infection does not simply mean we are no longer protected,” she said. “Our immune system is more complicated than that — which is a good thing.” 

A drop in detectable antibodies is actually expected after an infection and that high levels of antibodies remaining after an illness has passed could actually be a bad thing, Kelvin said.

“Typically, we would associate high levels of an activated immune response when there is no threat with more of an autoimmune disease,” she said. 

“So we do want to see somewhat of a decline to know that our bodies are in check after we’ve cleared the virus.”

The other important factor is that the immune system can actually remember how to make new antibodies when needed to fight off future infections, by storing types of protective white blood cells in the body called B cells. 

Kelvin said just because there aren’t detectable antibodies in the blood doesn’t mean we don’t have reservoirs of these immune memory cells stored in other parts of our body like in our bone marrow.

“That’s usually where your memory B cells would kind of hide out, waiting for another exposure,” Kelvin said. “Because you’re not going to have these circulating antibodies when you’re not being exposed, you kind of need to put them away for when you need them.” 

Conflicting studies cause confusion

Another study, published this week in the journal Science and peer reviewed, may have added to the confusion over immunity to the coronavirus. 

It looked at antibody responses in the plasma samples of more than 30,000 COVID-19 patients in New York City’s Mount Sinai Health System between March and October. 

It came to a much different conclusion than the preprint study: that more than 90 per cent of patients produced moderate to high levels of antibodies that were both powerful enough to neutralize the virus and lasted for many months after infection. 

WATCH | COVID-19 antibodies may disappear quickly, study finds:

A new study out of the U.K. has found COVID-19 antibodies can disappear quickly from people who’ve had the virus, which experts say makes herd immunity unlikely without a vaccine. 3:33

One difference in the two studies is that the preprint looked at patients ranging from asymptomatic to severe, while the published study focused on hospitalized patients who were primarily symptomatic. 

“There seems to be some type of split where milder cases after infection don’t have this notable increase in antibody responses for long periods of time,” Kelvin said. “That might be more evident in people who have more severe infection.” 

Researchers in the New York study concluded that the antibodies they found were likely produced by “long-lived plasma cells in the bone marrow,” something that backs up the idea that dormant immune memory B cells could be hiding there.

“This study suggests that the majority of those people infected with SARS-CoV-2 [the coronavirus that causes COVID-19] will produce protective antibodies, which will likely protect from reinfection,” Kelvin said. 

“This would support the notion that we will be able to produce a vaccine that is safe and leads to a protective immune response.” 

How our immune system responds to the coronavirus 

After an exposure to a virus from either an infection or a vaccination, the body goes through what’s called an “expansion phase” where these memory immune cells produce antibodies in response to it — something Kelvin likens to climbing a mountain. 

Once the body believes it has cleared the infection and reached the top of the mountain,  those antibodies then start to decline during what is known as the “contraction phase,” the start of the descent down the mountain.  

As you get to the bottom of the mountain, the body moves into a “memory phase,” where the most effective antibodies get stored until the next exposure — like the experience you might have to better climb the mountain next time.

At that point, B cells are not thought to be detectable in the bloodstream, instead going into immune reservoirs in the body such as bone marrow, which means they could be missed by researchers only focusing on antibodies in the blood.

“We don’t yet know what level of these antibodies is actually needed to prevent infection,” said Dr. Lynora Saxinger, an infectious disease specialist and associate professor of microbiology and immunology at the University of Alberta. 

“But there are lots of examples of low antibody levels getting boosted up quickly when you are re-exposed to an infectious agent due to B cell memory pumping out antibodies on re-exposure.” 

Another tool our body uses to help fight infection are T cells, a different type of white blood cell stored in the body that can also attack the virus the next time they encounter it but are a separate arm of the immune system. 

A recent paper published in the journal Cell found that a balance of both T cells and B cells produced in the body could lead to a better outcome after infection from the coronavirus, and Kelvin said understanding more about T cell immunity could be helpful for vaccine development. 

One positive note is that memory B cells, which have the capacity to protect against future infections, have already been detected in both symptomatic and asymptomatic COVID-19 patients, as pointed out in another study published in the journal Nature this week. 

Kelvin said COVID-19 patients who develop severe disease or die after being infected with the virus may have a lower ability to generate antibodies because it is possibly targeting and destroying those B cells. 

“These results would support the idea that ‘herd immunity’ through natural infection will not lead to long-lasting immunity,” she said. “Which will instead keep our vulnerable populations at risk of death.”  

Other coronaviruses, such as SARS and MERS, can also provide hints as to how long the dormant antibodies might stick around waiting to protect us from infection down the road. 

“In both SARS and MERS, for years after antibodies were no longer detectable, immune memory cells geared for specific responses to both viruses could still be found in recovered patients,” said Dr. David Naylor, co-chair of the federal government’s Immunity Task Force.

“Bottom line: It seems really likely based on millions of people infected, the duration of the epidemic and the still very small percentage of reinfections that there is pretty durable immunity to SARS-CoV-2 after an initial infection.” 

Vaccines safest way of achieving immunity

It’s important to keep in mind that research showing declining antibodies over time does not necessarily mean there is somehow less of a chance that we’ll be able to develop safe and effective vaccines in the coming months. 

“There’s still lots to learn about durability of immunity,” Naylor said.

No one expects any of the vaccine candidates to grant “indefinite immunity,” and they may work more like an annual flu shot, he said.

“The immediate issue is whether vaccines will achieve and maintain enough overall immunity to keep spread under control so we can get on with our lives.” 

Regardless, Kelvin says that immunity gained from vaccines is safer than achieving it through rampant infections, a concept also known as herd immunity. 

“More work is needed to understand how long immunity lasts,” she said, adding that while a vaccine might not offer long-lasting protection either, it doesn’t come with the same risk of death faced by patients with COVID-19.

“So having a safe and effective vaccine would be the best way of controlling outbreaks.”

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