Possible scenarios of the end of the pandemic

Vaccinations are our main hope of ending this pandemic. However, that does not mean that we will be finished withnSARS-CoV-2. There will still be many unvaccinated people, either because supplies in their country are limited, or because they refuse vaccination. In addition, vaccines do not always prevent transmission of the virus, and the length of protection after immunisation is yet to be clearly defined. These factors mean the virus may continue to mutate, in other words, to change its specific constitution. Will SARS-CoV-2 become an endemic virus with seasonal peaks? This is the most likely scenario.

Making predictions based on our experience of previous epidemics is difficult. We have existed alongside seasonal viruses, such as flu or other common coronaviruses, for a long time. However, SARS-CoV-2 is more virulent and more transmissible than common coronaviruses, but less so than SARS-CoV and MERS-CoV. The Spanish flu epidemic of 1918 also appeared in successive waves without seasonal peaks, but with much greater mortality. The H1N1 strain caused epidemics up till the 1950s, and was then succeeded by the H2N2 strain, from an animal reservoir. Furthermore, Poliomyelitis has never been eradicated, despite 2 effective vaccines, and without any animal reservoir.

It is also impossible to predict the next mutations of the virus with any precision, or to know whether its transmissibility, its virulence or its capacity for immune system escape will change. We have become familiar with spike mutations that increase the transmissibility of SARS-CoV-2, generating variants that become dominant throughout the world. These mutations are not necessarily linked to an acceleration in propagation, but sometimes possess a greater capacity for immune system escape. The effect of these mutations on other viral proteins is less well known.

However, there are other aggravating factors at work. The existence of non-immunised humans and animal reservoirs largely explain why effective vaccines are not able to completely eradicate certain viruses and halt their evolution. While it is clear that our immunity constitutes an element of selection pressure, influencing the development of SARS-CoV-2, other, more random events, may also cause it to take unexpected directions. SARS-CoV-2 has a relatively low level of mutation, but it is also capable of evolving by recombination, in other words, where two strains of coronavirus within the same host exchange fragments of their genomes. Such events may be multiplied tenfold in immunocompromised people (there are 10 million such people in the United States), who are contagious for much longer and may host more variants. In addition, SARS-CoV-2 is capable of infecting numerous animal species, providing it with additional opportunities for acquiring new properties (adaptive mutation or recombination with animal variants) which can then be reintroduced in humans. Such a scenario was responsible for 4 flu epidemics over the last century (in 1918, 1957, 1968 and 2009). The high number of humans and animals infected worldwide increases this possibility.

In the light of all these factors, what can we expect in the future? COVID-19 is likely to become a seasonal illness, but there is another possible scenario: if SARS-CoV-2 becomes endemic and co-evolves with our immune systems, it could also evolve in parallel in animals in different directions. Future generations will not be immunised against a new strain of SARS-CoV-2 deriving from animals. This is what happened at the time of the H1N1 epidemic in 2009: this strain, linked to the strain of 1918, had evolved in parallel in pigs. SARS-CoV-2 may disappear for several years and then return with new powers at its disposal.

If the first scenario turns out to be correct, then before SARS-CoV-2 becomes a seasonal virus, it is necessary that the vast majority of the population is vaccinated. The objective of the current vaccination campaigns is indeed to control the COVID-19 pandemic, not to eradicate SARS-CoV-2. They will drastically reduce the number of variants in circulation. In general, the more a virus is contagious, the greater herd immunity must be to stop transmission: 95% population immunity was necessary to stop measles, which is 3 to 5 times more contagious than the Wuhan strain. This points to us being able to control COVID-19 with a lower percentage.

So what do we need to do in the future? Repeated vaccination campaigns will be necessary in areas where there are outbreaks, as with poliomyelitis, or to compensate where there is falling immunity. Controlling the virus will undoubtedly mean vaccinating children since they are significant asymptomatic vectors. Close monitoring of reservoirs and antigenic drift will be required to identify dominant variants so as to update vaccines, as with the flu. Moderna is currently testing its vaccine which has been adapted to the Alpha (UK) variant.