Prof. Dr. Richard Neher. (Photo: Matthew Lee / Biozentrum, University of Basel)
Prof. Dr. Richard Neher of the Biozentrum at the University of Basel is using his Nextstrain platform to investigate which variants of the SARS-CoV-2 virus are currently circulating worldwide. The possibilities for future mutations are extremely diverse. Three variants of Omikron alone are circulating at the moment.
There is more and more talk about Omicron being the beginning of the end and the beginning of an endemic situation. What exactly does this mean?
When the pandemic becomes endemic, it means that a certain balance is established between the virus and us humans as hosts. The virus would circulate continuously worldwide, probably in waves in which the sometimes increasing, sometimes decreasing immunity of the population and the infections by the virus balance each other out. Endemic does not necessarily mean mild the poliovirus for example caused a severe disease and was endemic.
So it is not really possible to speak of an end then?
Of an end of the pandemic probably already. But the virus is not gone then. Rather, the virus will remain permanent and circulate recurrently, probably seasonally.
Are we already in such an endemic situation or is it imminent??
Our road to endemicity is bumpy.
The transition from pandemic to endemic cannot really be sharply demarcated. In other words, our road to endemicity is bumpy. The omicron wave is very steep, an equilibrium has not yet been reached. But we’re getting more and more to a point where almost everyone has some immunity- either by vaccination or infection. This reduces the burden of disease that the virus can cause. At the moment, however, the ups and downs are still too fast and the number of immunnaives is still too large to be able to speak of an endemic situation.
If this development occurs as it has, it is SARS-CoV-2 then to the population as the flu virus is?
There are similarities to the flu virus or other cold viruses, some of which are also coronaviruses. Our vaccination protection is weakening, on the one hand because the virus is changing, and on the other hand because of falling antibody levels. Even infections that pass through once do not offer permanent protection and re-infections with these viruses are not rare. How often we will be re-infected with SARS-CoV-2 in the future is not yet clear.
How severe is the course of the omicron wave compared to a flu wave?
The severity of future waves cannot be estimated at this time. It could be worse or less severe than the typical flu wave. This will determine how the "new normal" will look like looks like in the end.
Currently, re-infections are seen after a very short period of time. That’s why boosters are recommended after just three months in some countries. Could it be that in the future we have to get vaccinated every three months?
- Research group Prof. Dr. Richard Neher
I do not assume this. At the moment it looks more like we have a rather seasonal pattern, as with other cold viruses. In summer the virus circulates less and in winter we have smaller or bigger waves. Accordingly, there would then be a more typical time for booster vaccination in the fall.
For the entire population or only certain groups of people?
This refresher will be especially important for vulnerable groups like the elderly and people with pre-existing conditions. They benefit the most. Especially in view of the fact that the protection against the spread of the virus is obviously limited in time, the self-protection for these groups is even more important.
What would an endemic situation mean for our future life, apart from vaccination??
This depends on how strong these waves will be. The masks will possibly remain with us seasonally. Possibly, in the medium term, the spread of Corona and other viruses can be reduced by improved ventilation systems or other preventive measures.
What is different in the coronavirus than in the viruses whose spread you have studied so far??
- Research group Prof. Dr. Richard Neher
With no other virus have we seen this erratic evolution in such a short time so far.
With no other virus have we seen this kind of rapid evolution in such a short period of time. Variants like Omikron or Alpha have changed in many places without us observing precursors. Omicron shows 30 to 40 mutations in the spike protein, and Alpha also had ca. 10 mutations. Especially when a virus like SARS-CoV-2 is studied so closely, it is absolutely surprising when a variant with so many mutations appears out of nowhere.
Do we know more about the origin of Omikron??
What we do know is that there are three variants of Omikron currently circulating. Thus, in addition to the dominant variant, there are two sister variants that share about half of the Omikron mutation and have many additional mutations. So we have the main variant BA.1, a sister variant BA.2, which is relatively rapidly spreading and dominant in Scandinavia, India, and the Philippines, and finally a sister variant BA.3 with low spread. This alone makes the origin of Omikron even more mysterious. We cannot explain this atypical evolution until today.
Could there be another wave of Omicron with one of the two sister variants?
The variants are so similar in relevant regions of the spike protein that cross-immunity between these variants is highly likely. However, BA.2 to spread more quickly, and it could be that BA.2 continues to increase, becomes dominant, and causes a second peak. Or simply prolong the omicron wave a little bit.
What does this say about the future evolution of the virus?
It shows once again how versatile the virus is and that we must be prepared for further surprises.
From a purely virological point of view, isn’t Omicron a kind of "stroke of luck"?, with which an infestation could be risked?
Possible long-term consequences of the infection are also unknown. Vaccination is definitely preferable to Omikron.
Let’s say, if we had to choose, Omikron would be better suited for such a contamination than, for example, Delta. But that doesn’t mean all infections are mild. Also possible long-term consequences of the infection are unknown. Vaccination is definitely preferable to Omikron. It also looks like infection with Omikron does not protect well against infection by Delta or other variants- at least if there was no immunity to Delta prior to infection. So the omicron wave does not necessarily protect us from further waves in the future.
Could variants emerge that lead us back to point zero again?
This is very unlikely. Our immune system recognizes and fights the virus not only with antibodies, but also with its T-cells. And this T-cell immunity is much more difficult for the virus to evade, because our T-cells, unlike antibodies, recognize the virus on many different parts. In addition, different people’s T cells recognize the virus at different sites. Escaping a person’s T-cell response therefore gives the virus little advantage in spreading. Therefore, T-cell escape mutations spread very slowly, if at all, at the population level. With antibodies, this is different: here, most people recognize more or less the same spots on the surface of the spike protein. Mutations at these spike protein sites allow the virus to escape the antibodies of many people, and so these mutations spread.
Does this mean that we as a whole make it particularly difficult for the virus through different immune responses?
As for the T-cells for sure. And antibodies will also accumulate more diversity over time. Future variants will hopefully not spread as fast as Omikron does now. Evolution is always particularly fast when there is a consistent selection pressure in one direction. So once everyone has been vaccinated or infected with different variants, an immune escape variant can only reinfect a portion of the population.
Can future variants be predicted?
Omikron certainly surprised me and other scientists. But in the future, after we’ve learned more about the evolution of the virus and it’s a little more leisurely, this may be possible. We make such predictions for the flu as well.
What then are scenarios for future variants?
For example, a variation like Omikron could evolve, an old variation could be revived, or a completely new variation could evolve. Also possible would be the development of hybrids, i.e. the emergence of new variants through the recombination of old variants, something we already know from coronaviruses.
What would it mean?
It is possible, for example, that Delta will come back. Delta is a highly contagious variant that may have an advantage over Omikron again after some time, when immunity has waned. Unfortunately, deltaofter leads to severe expirations. Or we see a new variant with unknown properties. So we need to continue to closely monitor the development and emergence of new variants so that we can detect new variants early and understand their characteristics and not slip into a new wave unprepared. What these waves will look like, and when exactly they will come, cannot be predicted at the moment.
Richard Neher developed Nextstrain (nextstrain.org) in 2015 with his colleague Trevor Bedford of the Fred Hutchinson Cancer Research Center. The idea goes back to the research of flu viruses. The two researchers wanted to find out to what extent the evolution of viruses can be predicted. This is an important aspect, especially for influenza, because a new vaccine has to be developed every year.
Prediction is therefore of great importance. Nextstrain can be used to analyze the evolution and spread of various viruses, be it Corona, influenza, dengue, Zika or Ebola. Epidemiologists, virologists and public health experts worldwide are using this tool to see how pathogens are changing and spreading in near real time.