A powerful immune reaction called a cytokine storm is claiming the
lives of some coronavirus patients. Credit: ingimage

You’ve probably heard that your best defenses against the coronavirus
are washing your hands, practicing social distancing, and having a
healthy immune system. It’s that last part—the part you can’t really
control for sure—that may have you crossing your fingers.

A dysfunctional immune system, experts say, is one reason that
COVID-19 has proven more deadly in older adults and people with
certain pre-existing conditions. But it is not always that the immune
system is weak. Sometimes the body’s immune response is powerful but
so out-of-control that it ends up killing COVID-19 patients. What
exactly is going on?

Immunologist Pilar Alcaide, the Kenneth and JoAnn G. Wellner Professor
at Tufts University School of Medicine, says that because the
coronavirus is so new, we don’t fully understand how it works yet. But
researchers can draw on what they already know about the body’s
response to viral infections.

Here, she talks about aging and immunity, why obesity can make
COVID-19 more lethal, and a dangerous immune reaction called a
cytokine storm that is claiming the lives of some coronavirus
patients.

Tufts Now: How does the immune system normally respond to a virus?

Pilar Alcaide: The first immune response is very rapid. You have
immune cells that sense the virus as a strange agent, and they start
making a lot of things called cytokines to stop the virus. Some of
these cytokines kill cells in order to keep the virus from
replicating. One cytokine is IL-1beta—which, by the way, was
discovered at Tufts by Charles Dinarello—and that’s the cytokine that
turns your temperature up. A lot of viruses die at high temperatures,
so your body gives you a fever.

This first response is called innate immunity. If you think of it like
an army, it is your first line of defense. If the virus passes that,
that first line has previously coordinated with the second line of
defense—the adaptive immunity.

The adaptive immunity is a more specific response to this particular
invader to try to clear it. B cells generate antibodies, and T cells
help B cells make antibodies and can kill viruses themselves. If
everything goes well, you will kill the virus and you will develop
some immunity to it.

We know that older adults are more likely to die from the coronavirus,
in part because of their immune systems. What’s going on?

People who study aging know this phenomenon as immunosenescence. As
you get older, both the innate and the adaptive immune cells are not
as efficient at mounting a response to an infection.

In the innate immune cells, pathways that make cytokines don’t work
properly. It takes them longer to make the cytokines and by that time
the pathogen may have already invaded other cells. At the same time,
the innate immune cells don’t communicate as well with the adaptive
immune cells to mount that second line of defense.

Another important thing is that the immune cells are all derived from
stem cells in the bone marrow. And as you age, your bone marrow has a
smaller pool of those cells to draw on. That impacts how many immune
cells you produce.

Some people with COVID-19 develop a dangerous immune response called a
cytokine storm. What is that?

An effective immune system needs effector immune cells to fight the
initial infection, but you also need suppressor immune cells to turn
off those defenses. That’s what keeps people from having a constant
fever of 105 degrees; your fever starts high and then goes down
because your immune system is modulating, depending on how much of the
virus you still have. You have to have a balance of those effector and
suppressor cells, and older adults don’t always have that balance.

In a cytokine storm, your immune system thinks it needs to make more
and more of those cytokines, even though they are not sufficient to
stop the virus. It is a non-stop feedback loop. The virus is telling
your immune system, “You can kill me. Activate more and more and
more.”

Then, if the brakes stop working because the suppressor cells are not
getting their message across, any vulnerable organ can be damaged. At
that point, the virus may be not only in the upper respiratory tract
but in the lungs or heart. So then you have a flood of immune cells
going to those places.

Some of those immune cells are called cytotoxic T cells, because they
release toxic compounds meant to kill a virus. But if they release
them in a place where they shouldn’t be, then they damage the organs.
And that’s what some people are dying from. If you cannot turn off
your immune system, your own immune system can end up killing you.

The coronavirus appears to be more dangerous for people who have heart
or lung disease, which makes sense, but also for people who are obese
or have diabetes. How does having those conditions affect your immune
response to a virus?

Obesity and diabetes are strongly associated with a dysfunctional
immune system. If you look at the fat of a person with obesity or Type
2 diabetes, you will find a reservoir of T cells that make tons of
these cytokines. So that’s why they are at increased risk—most have
higher levels of proinflammatory cytokines.

The fact that they already have a high baseline means that they may
not have the suppressive function to turn off that inflammation if
they need to. So if they get an extra hit, it will be harder to stop.
They are already one level closer to this cytokine storm.

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Provided by Tufts University