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A hot take: This has been a good week in our battle against the coronavirus.

Yes, cases are at all-time highs in the United States, with deaths seeing the long-expected upturn. However, at the same time, we’re getting some really valuable, top-quality research that is helping us understand the disease more.

To put it in war terms: we may be losing the Battle of Arizona and Florida, but we just captured the enemy’s top codemaker and he’s spilling his secrets.

We’ve already looked at the recent promising vaccine news this week. Now, let’s talk about the evolving immunity picture. In particular, I want to break down the role of T cells in our immune response to the coronavirus. This is a bit sciency, but I hope you stick with me, because the payoff is worth it.

What are T cells?

The concept of antibodies is pretty familiar to most people by now: antibodies are proteins your body makes once you’ve had a specific bacteria or virus. If the antibodies encounter that virus again, they latch on to its particles to prevent them from causing havoc and they alert the immune system that something is going on.

But there’s another way our adaptive immune system works: T cells, called that because they mature in the thymus (our immune system’s primary organ, located just below your neck). These cells, like antibodies, also learn the properties of specific infections and then stop them.

Essentially, your body has millions of naive T cells waiting to encounter the disease they’ll be dedicated to. Once they do, they adapt to fit the shape of the infecting virus or bacteria. If they see that disease again, your body creates more of the T cells of that specific disease. Then they connect to infected cells and release toxins to kill them. Goodbye, compromised cell.

A graphic on T cells from ASU's
A graphic on T cells from ASU's "Ask a Biologist" site. The grey blobs are T cells with various keys that work against different viruses. The big spiky potato blob represents an infected cell. (https://askabiologist.asu.edu/t-cell)

So why have you heard so much about antibodies and not so much about T cells? For one, we understand the antibody response better because we’ve known about it for longer. It’s also easier and much cheaper to test for antibodies than it is to test for specific T cells. As a result, antibodies get the pub.

How many infected people have SARS-CoV-2-specific T cells?

Preliminary evidence is really good: it looks like nearly everyone in the disease severity spectrum develops T cells that adapt to SARS-CoV-2, the virus that causes COVID-19.

At the top, one study looked at 10 patients who were in the internal care unit and found that all 10 already had T cells specific to SARS-CoV-2. These T-cell responses happen quickly, too: these 10 patients had been sick for 5-14 days.

And at the bottom, there are people who only had mild disease. Another study looked at eight people who were household contacts of COVID-19 cases, all of whom tested negative for antibodies later. Some had mild symptoms they thought might be COVID, others did not. But despite not having antibodies, six of the eight tested positive for having T cells specific to SARS-CoV-2.

In fact, another larger study estimated that the number of mildly-infected people who have these T cells to be about double the number of people who have detectable antibodies. If true, it looks like serological studies are undercounting how many people have some adaptive immune protection to the disease. More on this later.

How long do T cells last?

One antibody finding that got a lot of attention was that coronavirus antibody levels tend to decline relatively quickly. In particular, a Nature study found that levels of one type of SARS-CoV-2 antibody dropped by about 70% in eight weeks in both symptomatic and asymptomatic cases. Other types of SARS-CoV-2 antibodies saw smaller, 10% declines in the same study.

Still, that drop off is notable, because it means we can’t necessarily count on antibody immunity to save us in the long-term. When we look back at the original SARS (a deadly cousin to COVID-19) in 2003, we found that antibodies lasted two to three years.

T cells seem to last longer than antibodies, though. In particular, we found people who had original SARS still had SARS-specific T cells in 2020, 17 years later. That’s generally what we’ve seen in researching T cells that adapt to other diseases.

How well do those cells work?

We don’t have any direct evidence on COVID-19, but here’s our best guess based on other viruses.

We can’t exactly expose the original SARS patients to SARS again, that would be evil. But we are willing to do that with mice, and we did in 2014. Eighty percent of mice with SARS T cells survived after being exposed to the virus, compared to 0% of those who didn’t have T cells. Those who survived experienced mild illness.

This is something we saw in the flu, too: humans who have virus-specific T cells are less likely to be infected and have more mild illness when they are infected, even decades later.

One compelling hypothesis for why COVID-19 impacts the elderly so severely is that T cell counts decline as you age. A 2015 study found 60–120 million types of T cells for people under 20, which dropped to 8–57 million in individuals over 70. Perhaps the loss of diversity in T cells makes it harder for the elderly to generate enough to fight the disease? It’s just a guess, but a reasonable one.

Can people get T cell protection without getting the virus?

It looks like it.

Remember how we learned that some people who get COVID-19 have SARS-CoV-2 specific T cells but not antibodies? Well, here’s another twist: some people have SARS-CoV-2 specific T cells but no history with the disease at all. That’s right — they have no positive test, no symptoms, no reported contact with a COVID-19 case, no original SARS, no nothing; but they still have T cells that would likely protect them from the disease to some degree.

That’s the finding of a Nature study released Wednesday. In 19 of the 37 people studied with no known link to the virus and negative tests, they found SARS-CoV-2 specific T cells. That’s more than half! It’s a big surprise.

What’s going on here? Well, one hypothesis is that these people had been previously infected with the mild coronaviruses that cause the common cold, and the T cells were created as a result of that. But the authors of the study seem to find that unlikely, because the specific shape of the T cells they find don’t match the common-cold coronaviruses that we know about.

Instead, they wonder if there’s been a very mild coronavirus or coronaviruses floating around before that are more similar to SARS-CoV-2, perhaps also of animal origin. It’s very possible that we wouldn’t know about such a thing if it weren’t killing people like COVID-19 is, but people who got that low-key virus would have some form of T cell protection against the coronavirus we are battling now.

If that were true, it would explain the seemingly random nature of patient outcomes — if you were lucky enough to catch the minor virus before, now you’re much more likely to be asymptomatic or mildly so. It might explain why some regions are harder hit than others; one place might have a higher percentage of people who caught the silent virus than another.

What’s left to find out?

So, so much.

For one, we don’t really know how representative that sample of 37 people is. That study is from Singapore. How many people in the U.S. have SARS-CoV-2-specific T cells? We need to find out.

We also don’t really know how protective T cells are against SARS-CoV-2, or even coronaviruses like it, in humans. Flu is a different kind of disease than COVID-19, and mice are pretty different than humans. We’ll be watching these people who have T cells to see if they can be infected, and if they are, what kind of disease severity they have. I think it’s reasonable to expect moderate but not total protection, but the answer could still be “no protection whatsoever.” We just don’t know yet.

There’s significantly more work to be done in terms of understanding individual variation in T cell responses — in particular, genetics seems to play a role. Can we know more about who is high-risk besides the usual calculus of age and preexisting conditions?

We also need to find out what kind of T cell response we get from our various vaccine candidates. If antibodies are relatively short-lived — and remember, it was only one type of them that showed huge declines — then we should also consider whether or not these vaccine candidates trigger T cell creation as a key factor in what vaccine we give people.

Still, this is a really promising field of research. It’s also really positive: any support our immune system gets from T cell protection above and beyond what we get from antibodies could make a big difference in how the pandemic plays out.

You may not have known about T cells before now, especially if it’s been a long time since your high-school biology class. But if you’re looking for reasons to be optimistic about COVID-19, T cells are one of the best things we’ve got going.