There are many big numbers associated with the coronavirus pandemic: tens of thousands have lost their lives, and millions have filed for unemployment. But there's also much smaller story playing out — inside the cells of those who contract the virus.
This microscopic, unpredictable story is what makes the coronavirus so deadly, and developing a treatment so challenging, experts say.
Unlike bacteria or fungi, viruses cannot live on their own — they require host cells to function. When viruses use human cells as hosts, they “completely take over all of the metabolic pathways of the cell to replicate itself,” explained David Leib, chair of microbiology and immunology at Dartmouth College.
“It would be as if somebody walked into a car factory and snapped his fingers and said suddenly, ‘You're making Twinkies!’ ” he said.
The coronavirus can attack the first cells it encounters in our nose or throat.
“It takes the virus roughly 10 minutes to get inside that cell and then to begin its replication cycle,” Leib said.
Then, he said, it takes eight to 10 hours to produce hundreds of copies of itself that go on to infect other cells in our bodies.
But while the virus is replicating and spreading, people are not necessarily aware. The World Health Organization says it can take between one and 14 days for a person to notice symptoms; the average is five days. And some people who are infected never develop symptoms.
Leib said it’s this period of time, when you do not feel sick but the virus is replicating, that makes coronavirus so dangerous and so hard to stop.
“You are a walking bottle of virus,” he said. “Any of your respiratory droplets would be quite infectious during that time, despite the fact that you feel well enough to go out and go to the store.”
After the virus breaks into your cells, some patients develop symptoms. However, many of the symptoms, including fever and aches, are actually a product of your immune system fighting off the virus rather than the virus itself.
“Many people have mild illness and after a week or so they feel a lot better,” said Shira Doron, an infectious disease doctor and epidemiologist at Tufts Medical Center.
For most people, Doron said, that mild illness seems to be it. The person’s immune system is able to see that the virus is hijacking cells and stop it.
But a small percentage of people have a second phase of the illness. They seem to be getting better until their symptoms begin escalating. The Centers for Disease Control and Prevention warns that “clinicians should be aware of the potential for some patients to rapidly deteriorate one week after illness onset.”
For many of these coronavirus cases — in which symptoms become severe — the body’s response to the virus may actually be more damaging than the virus itself.
“We actually, occasionally, find that people who are really, really sick from COVID-19, don't even have a positive test at that point,” Doron said. “It's not the virus really anymore that's causing the symptoms. It's the immune response to that invasion. We call it the cytokine storm.”
Cytokines are proteins that act like an alarm in the immune system, sending out signals and calling in reinforcements to fight an invader. In a cytokine storm, although the fight might need just one military unit, the alarm keeps going off and a massive army shows up.
“This immune overreaction is causing collateral damage. It's like friendly fire,” explained Leib. “It's just like any other urgent situation — an overreaction can be just as damaging as not reacting at all.”
Too many cells are recruited to fight off the invader, and the cells fail to respond effectively.
"The cells become exhausted very quickly,” said Galit Alter, a professor of medicine at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard. “They’re getting stimulated so hard by all these cytokines that the cells at some point almost poop out. And they are not able to completely participate in that antiviral response.”
In the lungs, this can look like a lot of inflammation — there is fluid accumulation where there is supposed to be air. That makes it very challenging for oxygen to transfer into the blood.
Unlike humans, Leib said, bats — which experts think are the source of COVID-19 — don’t get cytokine storm. "This lack of cytokine storm in bats may explain why they don't get sick, but we do,” he said.
Leib said one of the challenges of combating COVID-19 in humans is the fact that viruses hijack our cells.
“This is really the crux of the reason why it has been so hard to develop antiviral drugs, because almost any drug that will stop viruses dead in [their] tracks will also stop our cells dead in their tracks,” he said.
Doron, Alter and Leib emphasized how much there is still to learn about the virus. But Leib believes our best hope for fighting it is a vaccine that trains the immune system to recognize and eliminate the coronavirus before it can take hold — and before the immune system can call in that army.
