What to expect in the near future

In early 2021, the good news finally came before the Kovid-19 pandemic. The first vaccines are available and their expansion will begin worldwide, giving us hope that at the end of the tunnel we will see the light … Unfortunately, the joy is short-lived, and finally a disturbing transformation has emerged. 2020 “English” (variant of anxiety, B.1.1.7), later named alpha. Its increased transparency raised fears of an acceleration of the pandemic.

The historical variant (Wuhan) that locked our lives through the night had a root reproduction number of 3 or R0 (each infected person can infect an average of three). Unprecedented attempts by the population (detention, etc.) have brought this number down to less than 1, indicating that each patient is less contaminated than another person, which is promising for a decrease in the number of new cases.

Unfortunately, the alpha has 50% more transmissibility than the historical breed, reaching a base breeding number of 5. Then the delta appears (found in India), with the estimated base breeding number greater than 5. Each new variant, due in large part to its transmissibility, replaces its predecessor.

While 2020 is the epidemiological year of SARS-CoV-2, 2021 is undoubtedly the year of its evolution.

The emergence of variations, a common phenomenon and taken into account

Like all living things, viruses are constantly evolving. They adapt to their environment to maximize their campaign. But wherever vertebrate species take years, viruses like SARS-CoV-2 are infinitely faster – for example millions of times faster than our cells. This is a rapid but simple and predictable biological evolution that the whole world has observed for over a year.

This phenomenon has been widely reported in other viruses, such as influenza (flu) viruses. This is not without barriers to the control of these viruses, for which vaccines must be constantly updated.

In order to receive our responses to these phenomena, it is important to remember that recognizing new variations in a particular area does not mean that they have appeared there or that they are only roaming there. The example of Omicron is particularly glowing. Located in South Africa, it was also found in Hong Kong (confirmed November 15), Botswana (confirmed November 24) and after searching for it, health officials realized it had already spread around the world.

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The world fears three scenarios: increased transmissibility, infection-associated malignancy and / or immunosuppression

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Therefore the closure of air links will have a very limited impact on its spread… but on the other hand it may push many officials to no longer disclose this kind of information in order to avoid experiencing financial consequences. However, during an epidemic, rapid sharing of information is the best tool for preparing and adapting existing tools, especially vaccines and diagnoses.

Another important point is that it is important to classify the variants correctly: the transmissibility, virality, and efficacy of natural or vaccine immunity against different groups of the population is crucial in receiving multiple segmented responses (limitations, barrier procedures, vaccine, clinical preparation, etc.). And refers to the coordination of ministries).

Since the emergence of variants, the world has feared three scenarios: increased transmissibility, malignancy associated with infection and / or immune avoidance. So far, variations have been observed mainly with increased transmissibility.

Omicron case

In late November 2021, the invention of the Omicron variant triggered a global alert, as first data suggest that this highly contagious variant may cause more re-infections than others. If this really happens, it means that in addition to the high prevalence in immunocompromised individuals, those who have been previously infected or vaccinated are also at risk of re-infection.

With a very severe transmission and immunization escape, the epidemic is restarted – with its auxiliary limitations. However, this mutation does not appear to be associated with any specific clinical severity and, at present, it is still the 5th wave associated with the delta variant, leading to hospital satiety. The level of compliance with barrier policies and the progress of booster vaccine coverage have a major impact.

On the other hand, in the short term, a very strong spread of Omicron in an immunocompromised population exhibiting risk factors can cause harm to the health system.

Although previous variants have provided relatively “close” effects (a few other mutations), this variant is particularly different and has more than thirty mutations compared to the delta for spike protein alone. A surprise

The actual population impact on virus emergence

Although the evolutionary history of this variant is still unknown, many hypotheses related to the environment in which the virus was discovered seem plausible.

First of all, “gradual” evolution is possible. The observed mutations accumulate on a regular basis without being detected for months because they do not cause major epidemiological changes – in transmissibility, malignant or immunocompromised. In other words, a specific combination on a virus indicates a real turn for our immune system (ability to detect it, etc.) only after specific mutations have been reached.

This scenario is particularly prevalent in low-vaccination populations, where the virus can spread and travel through the most complex “adaptive landscapes” without slowing down – until the popular Omicron variant. These “landscapes” are combinations of thousands of mutations that the virus contains, each of which has an impact on epidemiological features that are difficult to predict. Knowing that the virus has about 30,000 base pairs, it corresponds to more than 8.1017 possible combinations … However, these combinations produce viruses with many identical features or are not viable, but the field of possibilities is vast.

Another possibility that has come to the fore many times is the implications of chronic infection in immunocompromised individuals.

In fact, some people with Kovid infection, especially those with an immune system defect (e.g. HIV, cancer, transplantation, etc.), may be infected for a relatively long time (several weeks to several months). However, if the virus develops when it is transmitted from one person to another, it can also develop in infected people. Therefore, patients with clinical forms identified by chronic infections may allow mutations to accumulate and thus produce a new mutation that is different from those that “internally” spread to the general population. And who are “locally” able to develop specific symptoms tailored to their own condition, particularly the ability to escape from the immune system.

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The more immunized the population is from the spreading virus, the more the variant that offers the competitive advantage will spread.

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It is very complex to test, but this hypothesis is biologically possible. We know that the intra-host evolution of HIV is very important and affects the diversity and epidemiology of viruses in the population.

Finally, the last possibility is an increase in selective stresses that are subject to the virus. In fact, the more immunized a population is from a contagious virus (either naturally or through a vaccine), the more likely it is that a variant (such as a greater transmission or immunosuppression) will exhibit competitive advantage.

Thus the most dangerous zone is at the intermediate level of immunity of the population: it exerts selective stress on the virus, which potentially promotes more dangerous mutations, but does not adequately inhibit its transmission to limit the virus. The emergence of new variations.

It is important to note that these explanations are not unique: each of these three evolutionary mechanisms contributes more or less to the emergence of each variant.

What does this mean for the current epidemic

New variants are likely to be identified in the coming months and they are likely to escape with significant immunity. Some mutations (receptor binding domain or RBD, 484K, K417N and L452R) have already been tracked in this regard. But even if vaccines reduce their effectiveness against infection, it is likely to continue to provide protection against more severe forms.

What is certainly clear is that the virus must be transmitted in order to thrive (and bring about variation). Of these, very different vaccination rates between different parts of the world leave significant space. Original vaccination strategies should be tailored to the different conditions of countries with limited or unstable resources.

It is high time to understand that this pandemic is playing on a planetary level and that the virus will never meet the boundaries that it cannot adequately penetrate.

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