by Samantha Ancona Esselmann, Ph.D., product scientist at 23andMe
From an early age, I knew my great-grandmother had superpowers. “Mimi,” we called her.
She was born in the late 1800s, earned a graduate degree from Berkeley in 1919, sipped a glass (or two) of sherry every evening, and charmed us with her wit until the very end. And, like her mother “Nanan” before her, Mimi lived to be over 100.
During the course of her remarkable life that straddled three different centuries and two millennia, she survived tuberculosis (which killed her father), the 1906 San Francisco earthquake, the 1918 Flu, retro-peristalsis (the reversal of intestinal smooth muscle movement), and two C-sections before the discovery of penicillin.
In her late 90s — coincidentally, during the late 1990s — she recovered from a broken hip, sepsis, and flu that would have felled a woman half her age. Well into her hundreds, she still walked every day, required no prescription medications, and ate ice cream every night.
I thought she was invincible
When she died at 103 shortly after a bad fall, it wasn’t an infection that killed her. It was organ failure. Her own body simply turned off the switch.
I think about Mimi — and her immune system — a lot. Apart from the obvious privilege that comes with being a white, middle-class woman in California, she lived a charmed life.
And while Mimi’s immune system never faced this coronavirus, I wonder if some people are just born better equipped to fight infection than others? After all, each of us has that family member who “gets sick a lot” and that one relative who is “never sick” (lookin’ at you, Mom).
We don’t know much yet about what factors can influence our immune systems’ responses to COVID-19. Research shows there are clear genetic differences in susceptibility to other infectious diseases — with much of that variation found in genes involved in the immune system. But our environment likely plays a big role in how well our immune systems function, too. Good news for me because I probably only inherited around 12.5% of Mimi’s DNA.
The more I learn about the complexity of the human immune system, the more I realize it may not have been a particularly “strong” immune response that saved Mimi. It might’ve just been the “right” response. After all, an overzealous immune reaction — like anaphylactic shock — can kill a person.
And an overzealous immune reaction seems to be contributing to COVID-19 deaths.
COVID-19 vs. the Immune System
When a person is infected with SARS-CoV-2 (aka novel coronavirus), the virus invades cells lining the patient’s respiratory tract and hijacks their cellular machinery to make more coronavirus, which goes on to infect more and more cells.
Next, the body’s immune system starts to take notice. But in some patients, the immune system gets carried away and they become sicker from their body’s own inflammatory response than from the virus itself.
Widespread inflammation of the lungs — triggered by a wave of inflammatory molecules in your body called cytokines — can lead to a condition called Acute Respiratory Distress Syndrome, or ARDS. In ARDS, the barrier between the blood and the lungs’ delicate air sacs breaks down and the lungs fill with fluid. This breakdown impairs the lungs’ ability to oxygenate the blood and clear carbon dioxide, which can lead to organ failure.
The drugs being deployed in hospitals to fight COVID-19 are not just experimental antiviral drugs like remdesivir.  Some of them are drugs that dampen the body’s immune response, in the hopes that they will give the patients a chance to take a deep breath (literally and figuratively) and get back to the business of fighting the virus.
During recent infectious diseases division grand rounds at UCSF, Dr. Michael Matthay, an ARDS expert and professor at UCSF’s Pulmonary Medicine department, speculated that once a patient has arrived in the ICU and developed ARDS, antiviral therapy may “not be effective.” Some experts think it may be more effective to intervene with antiviral drugs during earlier stages of the disease when symptoms are not yet severe. Or, perhaps an immune overreaction only affects certain patients, while others with severe symptoms could still benefit from antiviral treatment.
So what can make some peoples’ immune response to COVID-19 different from others?
Sex and the Immune System
We’re beginning to see clear sex differences in the rate of COVID-19 infection and mortality: not only are men more susceptible to infection by SARS-CoV2, but they are also more likely to die from the disease. In a recent European surveillance report from the World Health Organization, about two-thirds of COVID-19 deaths that week were men.
Some of these differences could be environmental. In many parts of the world, for example, men smoke more than women (which reduces lung health) and men are more likely to have preexisting chronic health conditions, such as heart disease, or high blood pressure.
But biological sex is known to play a differential role in the immune system. Women are much more susceptible to autoimmune diseases in which their own immune systems turn against them and attack healthy tissue such as rheumatoid arthritis, multiple sclerosis, and lupus.
At the same time, women often have a more robust immune response to pathogens like viruses and bacteria — a pattern that may be repeated with SARS-CoV-2.
Some researchers are speculating that women may have a stronger immune response to SARS-CoV-2 in the early stages of a viral infection than men. 
Compared to SARS (the classic kind), COVID-19 viral replication seems to peak earlier and at higher levels during the course of the disease, meaning an early and robust immune response could be the difference between life and death. 
A delayed immune response can be doubly dangerous. After the virus has a chance to wreak havoc in the lungs, an overzealous immune reaction can set off a widespread inflammatory response that causes further damage, accelerating progression to ARDS.
But sex is not the only variable that influences our body’s ability to fight infection.
Age and the Immune System
You’ve probably heard by now that mortality from COVID-19 is much higher among older people.  (Though it’s important to note that all age groups are susceptible to severe infection and young people can die from it too.)
Apart from being more likely to have chronic “comorbid” conditions such as heart disease, type II diabetes, or high blood pressure, older people are more likely to have dysregulated immune systems. 
Fewer precision-guided missiles. More carpet bombs.
While we may never be able to stop or reverse the aging of our immune systems — and genetics likely play a role that’s outside of our control — there are certain things we can do to slow it down and keep it in a “goldilocks zone” for as long as possible. 
Exercise. Get enough sleep. Avoid stress (where possible). And eat a healthy diet.
Not too hot. Not too cold. Just right.