It has been several months since a coronavirus called SARS-CoV-2 arrived to change our lives. Although scientists do not tire of saying that we saw it coming, the truth is that deep down this situation has caught us as unprepared as the rest of society. Overnight questions rained down on us about what is happening to us and what should we do next. And, unfortunately, no one was prepared to answer them.
It is true that now, thanks to research, we know much more than at the beginning. Among other things that the virus is transmitted by aerosols, how long the incubation period lasts, that we generate immunity after infection, and we even know how long the virus lasts on a coin (4 hours). But one of the most important questions still remains without a definitive answer: why do some people pass the infection without knowing it while others get sick and die?
We tend to simplify by assuming that risk factors predict the severity of COVID-19, assuming that severe cases are only those with cardiovascular or respiratory diseases, diabetes, immunodeficiency, advanced age … And yes, of course, all this aggravates. But the real question is: why do these medical conditions make COVID-19 more serious? We still do not have it completely clear.
To top it all, there are those other cases that we hear every day of people who die with no known prior pathologies. Those “were very healthy and yet COVID19 killed them” or “some young people and children also become seriously ill.” The fact that we continually hear exceptions shows – let’s face it with humility – that we still do not fully understand the true reason for the greater or lesser severity of COVID-19.
How our defenses work has a lot to do with how we get sick
One of the keys to understanding why COVID-19 causes seriousness in certain cases is knowing how our defense mechanisms react to infection. The first thing that happens when the SARS-CoV-2 virus enters our body is that it activates emergency defense mechanisms. It is what we usually call innate immunity. It is made up of reflex acts such as coughing, molecules and “off-road” cells that are quickly recruited and that are capable of acting against all kinds of aggressions to our body. It would be something like calling 112 in an emergency: a quick response to an immediate and poorly defined danger.
Once the problem has been identified, our second response mechanism, acquired immunity, acts. At that moment, our body knows the aggressor and generates a more appropriate response. It would be something like recognizing that the danger is a fire and calling the fire department. Until then, we all react more or less the same. But what happens from this moment on is what makes the coronavirus sick more or less seriously.
To follow the fire metaphor, how to put out a fire depends on many things. How big is the fire? What material is burning exactly? How many firefighters do we have available? Biologically, this means that the body has to decide how to mobilize against infection.
In this sense, the most important signals (our firefighters) are a group of molecules called cytokines that are responsible for organizing defenses in proportion to the severity of the problem. As in any alarm situation, the activity of emergency units can cause a bit of chaos. Who has not ever been affected by a street blocked by a fire engine or a loud siren in the middle of the night? But generally we all understand that it is something necessary to put out a fire.
In our body, chaos would be generated by inflammation . And we all understand that the symptoms of inflammation, although bothersome, usually mean that our defenses are at work. In healthy people before infection, this inflammation is usually quickly controlled with efficient management of the infection. But in some people too many defensive resources are mobilized and inflammation becomes a problem as well. When our firefighters, cytokines, get out of control, they can cause even greater chaos than infection alone and disrupt many other bodily functions.
In short, that poor management of the infection is the cause that the symptoms of COVID-19 are worse. That is why some people with saturated immune systems or inflammatory processes prior to the disease can become more seriously ill and die.
What can we do to control inflammation?
Let’s not blame the firefighters, sorry, the cytokines. After all, they only do their job to the best of their ability. To deal with the problem, what is needed is better control of inflammation. To do this, some scientists are exploring ways to inhibit cytokines, but this is a partial solution. Because we all need our firefighters during a fire.
An alternative solution is to control what controls cytokines, that is, cells. Which in our metaphor would be the citizens who call the emergency room. When cells are stressed by infection, they call up cytokines, and the more stressed they are, the more insistently they call them, causing that uncontrolled inflammation. That is why one possibility to treat COVID-19 is to reduce the stress of the cells.
There are many drugs already approved that reduce cellular stress, which brings us closer to a drug that improves the hopes of recovery of seriously ill patients with COVID-19.
Predict gravity
But there is even more: people who already have diseases that cause stress to cells and are infected by the coronavirus have a greater chance of getting sick and dying. This conclusion may sound hopeless, but scientists tend to put a good face on bad weather. And it has occurred to us to use it to detect this stress in people in the initial stages of infection and predict whether they will develop severe symptoms or pass the infection asymptomatically or with mild symptoms.
Knowing if the patient suffers from cellular stress we would kill two birds with one stone: we would detect gravity before it happened and we would treat it in time. But let’s not get ahead of ourselves. Because there is still a lot of research to be done, and the scientific method requires patience. That is why scientists tend to delay when they ask us: and the remedy, by when?
Iván Durán, Professor in Cell Biology, Genetics and Physiology, Universidad de Málaga
This article was originally published on The Conversation. Read the original.
