Ulrich Elling is one of Austria’s leading experts on coronavirus mutations. With his team, he has developed a mass test procedure for Sars-CoV-2 and the detection of virus variants. “SARSeq” is the name of the monitoring system with which he carries out 80 percent of virus sequencing for Austria at the Vienna Institute for Molecular Biotechnology. In an interview, the molecular biologist sheds light on the future of the pandemic.
“Wiener Zeitung”: At the beginning of the pandemic, many experts believed that coronaviruses rarely mutate. Now one variant chases the other. As soon as we have Alpha under control, Delta is pushing up the number of infections. Why is Sars-CoV-2 suddenly willing to mutate?
Ulrich Elling: Sars-CoV-2 changes significantly less than other viruses with two mutations in the genome per month. In the flu, for example, there are six mutations a month. Sars-CoV-2 has an enzyme that checks that no errors occur during the replication of the RNA. In contrast to the flu, no genome sections can be mixed up incorrectly with the coronavirus because it only has one genome. The reason we still see a lot of mutations is because there are so many viruses. It’s that simple.
So are the numerous cases an experimental field for the virus?
Yes. This gives the virus a lot more opportunities to try out what is possible. If I remember the first HIV drugs in the 1990s, the patients were fine for a while, but then they got AIDS anyway. There is no resistance to the new HIV drugs because they lower the virus level in patients so much. Where no virus reproduces, the likelihood of a mutation is much lower.
Where do the mutations arise?
Mutations arise randomly in every patient. That doesn’t mean they’ll get any more infectious right away. But if a mutation gives the virus an advantage, the virus will multiply faster.
And what’s next?
Normally there is a dependency in evolution: when rabbits reproduce, the foxes reproduce and eat them too, which is why there are fewer hares and the foxes have less to eat. There is no such interaction between virus and humans. It takes 30 years from one generation of people to the next, and a few hours from one virus to the next in the patient. Viruses just want to multiply. They don’t care if people get sick in the process. But if they get too infectious, it turns into a forest fire. The viruses burn through once and only leave behind dead or immune, which leaves them dry. A successful virus doesn’t want to be too infectious so that it doesn’t burn itself into a corner. In this sense, it can evolve to adapt to people.
How do the viruses adapt?
Sars-CoV-2 has learned to reproduce not only in bats, but also in humans, and now wants to get into cells more efficiently and escape the immune system, which is increasingly doing better with alpha, beta, gamma and delta. In the very next generation – a few hours later – it can also test whether the attempted adaptation is effective. Especially when an immune system cannot fight the virus well, it coexists with that person and mutates all the time. This creates the complex variants that have prevailed up to now. This game will go on as long as we let the virus.
There are people who do not get Covid-19 because of their genetics or blood type. Does the adjustment also happen the other way round?
Of course, some may be preferred. In general, however, the virus genetically adapts to humans, but we do not to the virus. Our immune system can learn to deal with it, but we as humanity cannot react in an evolutionary way to Sars-CoV-2 in the foreseeable future. Evolution would mean that over generations, the weak would always die and only those left who were resistant to the coronavirus. We cannot allow that to happen.
The virus is so fast that it is always ahead of humans.
Exactly, and its goal is balance. It actually wants to go exactly where the influenza is: In winter it spreads with an R value of 1 (one person only infects one more, note), so that there is new food for influenza. If we let Corona there, it would be a long game. Instead, we alternate between measures and openings in order to suppress the prevailing, milder variant, while variants that are more disadvantageous for us inevitably develop. Mutations that bypass immune protection will also arise. They don’t exist yet, but they are coming.
But this perspective already frightens me. It has always been said that the vaccinations work. Do we have to reckon with corona mutations that circumvent the vaccinations with which we hope to end the pandemic?
Months pass before a variant becomes established. All the variants that we know to this day were created last autumn. Even then there were the first sequences of alpha, beta, gamma and delta. However, there was no relevant immune protection through vaccinations or surviving infections. Previous variants have therefore primarily been optimized for higher infectivity. Only now have so many people in some countries been vaccinated or recovered that the immune protective shield is effective. And so the virus only now has strong selection pressure to generate vaccination resistance in order to be able to infect the largest possible population. There is certainly still a lot to come. I expect such mutations from winter onwards. They should start reproducing now.
Will we still deal with Delta next winter?
I do not expect it. Rather, I assume that mutants are now developing into mutants. Alpha, beta, gamma and delta formed in the original Wuhan virus, which no longer exists. A very aggressive new alpha version can now emerge and displace Delta, or Delta can pick up speed and displace the others.
How does a mutation circumvent vaccination protection?
When infected, you are exposed to all coronavirus proteins. We only vaccinate with the spike protein on the surface, with which it paves its way into the cells. When a spike protein mutates at several important binding sites for human antibodies, it reduces immune protection. And if several of these positions are impaired, antibodies can no longer bind there. The virus escapes the vaccine and enters our cells.
Has herd immunity always been an illusion?
In March 2020, one person infected three others. If two were protected by a vaccination, the infection rate R would be 1 and then there would be no more exponential growth, it was said. Therefore, a 70 percent vaccination quota must be achieved in order to stop the spread. Delta is more infectious: One person infects six people, which is why we have to immunize 85 percent of people effectively so that the chain is broken. However, the vaccination works a little worse against Delta. The probability of not getting sick is 60 percent with Astra and 88 percent with the mRNA vaccinations, the protection against infection is slightly lower. That means: Even if we vaccinate 100 percent of the population, we will not get the 85 percent that we would need to break the chain of infection. The subject of herd immunity is over.
And how do we get the virus under control now?
Now it’s about individual protection. The vaccinations continue to protect very well against severe courses. Since the infection rate with Delta is twice as high as with Alpha, anyone who is not vaccinated is at great risk. Because of this, we probably need a mandatory vaccination. There are moments when you cannot leave people to their own devices with a clear conscience. It’s like in traffic: there we force them to buckle up or not to cross the street when it is red. It can be assumed that we will have a massive wave in autumn that we cannot easily narrow down. The seasonal effect is responsible for 40 percent of infections. In winter Delta and her successors will blow our minds.
That means lockdown for years?
We will not be able to afford that economically.
What’s the alternative?
There is also a human experiment going on, which I do not consider ethically acceptable, in England and Spain. Both countries have extremely high incidences among boys, but the party continues anyway. The hospitals in England are already filling up. The elderly are vaccinated, but we do not know whether they are adequately protected. Not all of the young have been vaccinated yet and they will carry the epidemic to the elderly with a delay. The question will be how many dead and long-covid patients versus how much lockdown society will accept.
Is there a point where Sars-CoV-2 no longer changes?
It has mutated when there is no virus. That must be our goal. Until then, it can continue to play and we don’t know where it’s going. With alpha, beta and gamma we thought that a change at position 501 was crucial for greater infectivity, but Delta does not have this mutation. We have to depress the virus population, and that means helping all countries to vaccinate. That is the only solution: vaccinate worldwide. All.