A new corona wave is rolling over Germany. This is due to the omicron subvariants BA.4 and BA.5. Now there are first indications that these could not only be more contagious, but also more pathogenic: Because they may trigger more severe disease courses than BA.2.
High number of infections, but predominantly mild courses – Omikron almost seemed to herald the end of the pandemic. But new omicron sublines keep popping up that are even more contagious. After BA.2 was dominant in the past few months, the proportion of BA.4 and especially BA.5 is now increasing sharply.
According to the current weekly report from the Robert Koch Institute, the proportion of BA.4 and BA.5 in particular in the infection process is doubling weekly in Germany: 4.2 percent of all infections can already be traced back to BA.4 and almost 24 percent to BA.5 . The share of BA.2, on the other hand, has now fallen to 70 percent – a few weeks earlier the share was still over 90 percent. So this shows that the new variants are significantly more contagious than BA.2. According to the RKI report, there are still no indications that they also cause more severe illnesses and more deaths.
But the physician Jan Hartmann sees it differently. “There is increasing evidence that [the] intrinsic severity of BA.4 /.5 is moving towards delta again,” he wrote on Twitter. One reason for the less severe course of the BA.1 variant, for example, is with high probability that the virus had changed its preferred entry route into the cell, he continues.
Instead of “endomal fusion”, the focus would again be on the entry route of the virus into the cell using the enzymes ACE2 and TMPRSS2. This is very likely to lead, among other things, to a stronger lung attack, writes Hartmann. “It’s like a viral yo-yo,” said Stuart Turville, an associate professor at the University of New South Wales, commenting on this renewed change in how the virus enters the cell.
A much-discussed preprint study from Japan, which was published at the end of May, also indicates that BA.4 and BA.5 could possibly lead to more severe courses. Accordingly, infection experiments with hamsters showed that BA.4 and BA.5 are more pathogenic than BA.2. This means that they trigger a more severe course of the disease than BA.2.
Another result of the study is also worrying: According to this, a previous infection with BA.1 or BA.2 is of little use against these two new sublines. “Neutralization experiments showed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5,” it says. People who have been infected with BA.1 and BA.2 are therefore significantly less protected from infection with BA.4 or BA.5.
An American preprint study, which was also published at the end of May, points to another consequence of these modified subvariants. “The fact that the novel omicron subvariants carry additional mutations in their spike proteins raises concerns that they may further evade neutralizing antibodies, further compromising the efficacy of our Covid-19 vaccines and therapeutic monoclonal agents,” it says .
Systematic analyzes have shown that BA.4/5, which already dominate in the USA and South Africa, are significantly more resistant to sera from vaccinated and boosted people than BA.2, for example, and are therefore more likely to lead to breakthrough infections. Those who are vaccinated and boosted therefore have even less resistance to the new sublines than they have to BA.2.
Friedemann Weber from the Institute of Virology at the University of Giessen also confirms that BA.4 and BA.5 should not be underestimated given the current rapidly increasing number of cases in Germany. “According to previous data, these two variants, which are now becoming dominant, are unfortunately very contagious and possibly also more pathogenic,” he told FOCUS Online. “It is therefore quite possible that the current increase will continue for a while and also lead to an increase in deaths – as can be observed in Portugal,” Weber continues. Despite the high vaccination rate, Portugal in particular has experienced a sharp increase in infections in recent weeks.
Still, Weber does not expect BA.5 to escalate the situation to pre-vaccination levels: “Thanks to vaccinations and also because of previous infections, we have a certain population immunity and are therefore far removed from the magnitudes that existed in winter 2020/21,” he explains.
Weber therefore does not believe that, given the increasing number of infections in Germany, the health system could be overloaded this summer. “However, there could definitely be restrictions due to staff shortages or local outbreaks,” he restricts.
The Frankfurt virologist Sandra Ciesek also admits that BA.5 in particular could be potentially more dangerous because of the mutations at the key points of the spike protein, as this enables it to infect lung cells better. “I think it’s possible that BA.5 could be a little more pathogenic again, but that hasn’t been finally clarified,” says Ciesek in the latest NDR podcast.
However, due to the change in immunity in the population due to vaccinations and infections that have gone through, it is difficult to compare whether the subline actually makes people sicker than Alpha or Delta. And even if BA.5 should cause more serious diseases again, the virus could still cause less damage than it did two years ago, when there were no vaccinations, antiviral drugs and monoclonal antibodies, according to the virologist. The increase in deaths in Portugal could possibly be related to the fact that many older patients whose booster was a long time ago have not yet received another one, the podcast continues.
Virologist Ulrike Protzer from the Technical University of Munich gives the all-clear despite the worrying situation that BA.5 has caused in Portugal with rising hospitalization rates and deaths. “If I have a lot of infections, I will always have patients who come to the hospital and I will always have more severe courses,” she told Bayerischer Rundfunk. This effect is to be expected when new variants such as BA.5, which are even more contagious, appear.
Whether these omicron sublines are actually more pathogenic and make us more seriously ill cannot yet be said, says Protzer. However, the new variant reminds us that we need a sensible infection protection law in autumn with clear key figures as to when measures have to be introduced and when not, according to the expert.
However, she does not see the danger of nationwide lockdowns and even school closures. “It will not happen again that we come back to a situation like the one we had at the beginning of the pandemic, because the immune system is well prepared across the board,” says the virologist.
