Researchers knew that these so-called cytokine storms were damaging, but they didn’t know why the SARS-CoV-2 virus seemed to be so good at setting them off.
The study revealed that the SARS-CoV-2 virus can infect certain kinds of immune cells called monocytes and macrophages.
Monocytes and macrophages are white blood cells, and they are frontline workers of the immune system. Their job is to circulate in the blood and tissues, to find and destroy pathogens. They do this by eating — or really, surrounding and absorbing — threats like viruses to keep them from being able to infect other cells.
Once a bad actor is absorbed, these cells have what can best be described as a cellular garbage disposal, called an endosome, that normally shuts the infectious agent down.
In the case of the SARS-CoV-2 virus, however, that doesn’t happen. The virus gets out of the endosome and escapes into the body of the cell, where it starts making copies of itself.
“The viruses not only get taken up, but once they get taken up, the virus starts replicating, so that was surprising,” said Dr. Judith Lieberman, a pediatric immunologist at Boston Children’s Hospital, who led the research.
A virus starting to make copies of itself in the body is never a good thing, but when this happens to these protector cells, it sets off a next-level set of alarms.
A fiery death
These alarms, in turn, summon agents called inflammasomes that, in essence, respond by burning it all down. They help the infected cell die by pyroptosis, or “fiery death.”
Pyroptosis is a newly recognized phenomenon. It happens in other diseases, too, like sepsis.
“When cells die by pyroptosis, they release all kinds of inflammatory proteins that cause fever and summon more immune cells to the site,” Lieberman said. It sets off a cascade of crisis signals that’s very difficult to stop.
“We don’t have any way of treating that once it gets started. It’s just sort of it’s like a little fire. It spreads and explodes and no fire extinguisher is capable of putting it out,” she said.
“I think it’s really elegant,” said Donna Farber, a professor of microbiology and immunology at Columbia University, describing the study. “They actually put some pieces together that hadn’t been put together before.” She was not involved in the research.
In comparing the blood cells of healthy people to those of both people who came hospital with Covid-19 and the blood of people who had pneumonia from other causes, researchers found this process seems to happen more often with Covid-19.
“All the patients we studied had signs of respiratory distress and pneumonia. The ones who had [SARS-CoV-2] had many more of these inflammasomes and dying cells,” Lieberman said. “So it’s likely that [SARS-CoV-2] is particularly good at inducing it, but we don’t know why.”
Lieberman said that the study also helps to explain why people who are older or have underlying health problems like obesity or diabetes have higher risks for severe outcomes with Covid-19. Those conditions are already associated with some level of inflammation in the body.
“They’re much, much more likely to start these inflammatory fires,” she said. “They have sort of a low slow burn going on…