That omicron is less virulent than the previous variants we’re probably all heard over the past month. But are we sure of such information? On what do we base ourselves to confirm this?
The virulence of an infectious agent is understood as a measure of pathogenicity. We understand that something is pathogenic when it can cause an illness or a harmful effect. For the infectious agent to be a pathogen, two elements are needed: the infectious agent and its host.
The power of a new variant
The intrinsic virulence of SARS-CoV-2 depends on its potential to replicate in the cells that infect it, to evade our immune response and to induce a type of abnormal response caused by covid-19.
Among the intrinsic virulence elements of the virus, we find two types of proteins: the structural one, present in the viral particle, and the non-structural one, which is produced only during the virus replication process in the infected cell.
This process involves a very effective interaction and manipulation of proteins and cellular processes by viral proteins. For example, protein S, which interaction with the ACE2 receptor or the PLpro protease, which cuts and serves to mature different viral proteins, as well as cuts and inactivates some key cellular proteins. Also ORF3b and Nsp14which is involved in the inhibition of defense mediated by autophagy, the paralysis of the production of cellular proteins or the response mediated by interferon.
The list of virulence factors is long and will involve the elements of the virus that alter the normal functioning of the cell and of the infected organism associated with the disease.
The other side of the coin: our immunity
The various layers of immunity we have against infections act like an army trying to reduce the impact of viral weapons.
The three main hosts we have are innate immunity, humoral immunity (mediated by specific antibodies), and cellular immunity (mediated by T cells).
At the beginning of the pandemic we only had innate immunity to protect us from any virus. If overwhelmed, the other two may come into action, but they need training time to specialize in combating SARS-CoV-2. At that point, they were not ready and could not avoid covid-19.
Both vaccination and infection function as a training course for this defense. In this way, the generation of antibodies and specific T cells against the virus is selected and improved. To the extent that preparation is improved, the immune arsenal allows our three armies to have the necessary training to defy the enemy with guarantees to be able to control it and prevent it from harming us.
Depending on whether we are immunized or not, the damage caused by the virus can vary and therefore its virulence will change in us as well, as it, as we said, depends not only on the virus but also on the host.
In other words, the virus can still have very powerful weapons, but our immune preparation can cause it less damage.
Less virulent, but not much
In recent weeks, it has been repeatedly heard that the omicron variant is “weaker” than the previous variants. But that does not mean that it has lost all its virulence, or even a good portion of it.
According to a last study (a prepress not peer-reviewed), performed in animal models, the virulence was slightly reduced. Also another research (also prepress) confirmed that much of its virulence and the severity caused by it only reduced the risk of hospitalization and death by 27% compared to the delta variant.
In fact, we can observe a higher percentage of people in ICUs who have not been vaccinated or who do not have prior specific immunity to the virus, and even die, compared to vaccinated people with the same characteristics. In other words, it is in them that the intrinsic virulence of omicron is revealed.
How is it different from previous variants?
In each of the variants that appeared from SARS-CoV-2, the virus introduced mutations that allowed it to displace the previous variant due to its efficiency in infection and spread.
Alpha has obtained improvements in transmissibility against the original Wuhan virus. Delta, in turn, gained the upper hand thanks to improved infectivity and partial ability to evade some of the neutralizing antibodies.
Now omicron has managed to maintain and even improve its transmittance and evade the neutralizing capacity of specific antibodies against previous variants. It did so by introducing most of its changes to the surface protein.
But none of these variants appear to offer an improvement in the intrinsic properties of the virus to evade innate immunity and have only achieved gain a small ability to overcome cellular defenses.
In short, the intrinsic virulence elements of the virus that could be altered by mutations in the different variants were not sufficient for the virus to lose much of its virulence as shown by omicron in non-immunized humans.
Much of the virulence of the various variants is conditioned by our preparation against the virus. It is therefore expected that the long-awaited loss of virulence will be largely determined by us and our ability to develop immunity, after infection and after vaccination, and that this will be the determining key to overcoming the pandemic.