Recent Research on Sheds Light on Things That Can Determine the Severity of COVID-19
As you probably know, SARS-CoV-2 has a wide range of severity levels. Some never get it despite exposure and lack of vaccination. Some people get asymptomatic cases, some get mild cases, and some get quite severe cases.
Scientists are trying to work out explanations for these things. Two recent stories summarize this work.
First, there is work on the never-COVID people. This NPR story talks about research exploring two reasons why some people never get the virus even though they are chronically exposed.
One study showed that exposure to other coronaviruses—the kinds that can cause common colds—might prime the immune system to fend-off SARS-CoV-2. It looked at the blood of about 60 health care workers at a hospital who were repeatedly exposed to the virus (before vaccines were available) but never fell ill.
Analysis of their blood showed the presence of an immune cell called a cross-reactive t-cell. Workers who did become ill did not have these cells. Since SARS-CoV-2 is a "novel" virus, it's likely that the cross-reactive t-cells developed in response to a previous infection with some other coronavirus.
Second, there is an "innate" immune mechanism called a RIG-I pathway that can detect a virus, bind to its RNA, destroy it, and trigger an immune response that keeps it from spreading to neighboring cells. It has been shown to be operational in lung cells.
Everyone has RIG-I receptors but it appears that they are more robust in certain people, for example younger people. One study found that kids have more of these receptors in their nasal cells, compared to adults. This is possibly one reason why kids are less likely to have serious infections.
The other story looks at what is going on with the unlucky people at the other end of the spectrum who have severe infections because their immune systems don't shut down the virus early on. I know two such people, one of whom came close to being put on a ventilator and another who developed long COVID because of lung damage.
Researchers have found that there are two types of immune cells—macrophages in the lungs and monocytes in the blood—that can themselves become infected with SARS-CoV-2. When this happens, the infected cells freak out (my words, not the scientists') and trigger a massive inflammatory response that can damage nearby healthy cells.
Immune cells don't usually have many of the ACE2 receptors the virus uses to infect most cells, so it was unclear how the virus was getting in. Researchers aren't sure but have found some evidence that the immune cells scoop-up virus particles that have been attacked by an antibody meant to disable the virus!
This is a dastardly process because normally antibodies can be important in phagocytosis, the process by which a macrophage engulfs and destroys an invader. So far as I can tell the studies described in the story do not explain how the virus evades destruction and instead invades the immune cell.
