The student didn’t really stand out among the nearly 700 cases of the coronavirus recorded by the public health department in Berlin’s Steglitz-Zehlendorf district during the week before Christmas. The young woman was home for the holidays to visit her family, having traveled back to Germany from the university where she is studying in the United Kingdom. It appeared to be an everyday case of the coronavirus in the affluent southern part of Berlin.
Indeed, it wasn’t all that surprising she had caught the virus, given that infection numbers were skyrocketing in Britain at that point.
But the student also infected her entire family, five people, which is pretty uncommon.
Just as her infection was discovered, British Prime Minister Boris Johnson had begun sounding the alarm: B.1.1.7, the new and far more contagious variant of the virus, was spreading in southeast England, he warned. The response came quickly: Flights to and from Britain were cancelled and the Eurotunnel was closed to traffic. By then, though, the mutated virus had long since begun spreading across Europe.
It was by coincidence that an employee at the Steglitz-Zehlendorf public health department had experienced the ebola pandemic in West Africa and had also earned a doctorate in virology. Shortly before Christmas, she made a call to the laboratory at the Robert Koch-Institute (RKI), Germany’s center for disease control, and asked to have the genome sequence of the student’s positive viral sample decoded.
The result arrived on Jan. 7. The student was found to be carrying the new B.1.1.7 variant of the virus.
Then, last week, the first case of B.1.351, a mutant of the coronavirus from South Africa, was detected in the southern German state of Baden-Württemberg. It’s also thought to be much more contagious than previous variants. It had been brought into the state by a family that had arrived back from South Africa in mid-December.
The family had quarantined themselves as required under coronavirus regulations, and five days later they received a negative result after getting tested. But family members developed symptoms of the disease a week later. By then, six people from three different households had been infected.
In the neighboring state of Bavaria, there are also now three confirmed cases of coronavirus mutants and one suspected case. One patient who had become infected with the British variant was brought to a Munich hospital for treatment around the New Year has since passed away.
"The new variant of the virus has arrived in Germany," says Clemens Wendtner, chief physician at the München Klinik hospital in Munich’s Schwabing district. It must be a feeling of déjà-vu for the physician, who also treated the very first known German COVID-19 patients last February. "The next few weeks will be decisive,” Wendtner says. "It's possible that the pandemic will take on a whole new momentum.”
Three different new mutants of the novel coronavirus have begun spreading at break-neck speed around the world. They have two things in common: a very specific mutation – and they are far more effective at infecting people than previous versions, with the new variants likely up to 56 percent more infectious. There are also worries that they could prove less susceptible to some vaccines and that people who have already had COVID-19 could get infected again.
The cases that have been imported into the country so far demonstrate that it’s likely impossible to seal Germany off from the new variants. It’s probably just a matter of time before the super viruses begin spreading in Germany and Europe. And it’s quite possible that this has already happened.
For a long time, it seemed as if the world knew its enemy – a coronavirus that could be compared with its ancestor SARS and other coronaviruses like MERS. In small steps, we became more familiar with how the disease spreads and what we can do to best protect ourselves. We got to know the virus right down to the last molecule – so well that researchers were able to develop vaccines in record time, promising to help humanity out of the permanent lockdown.
We would, it seemed, bring SARS-CoV-2 under control in 2021.
Now, though, the virus is mutating – unfortunately in a direction that is likely to lead to many more victims.
There’s nothing particularly special about mutations, mutating is what viruses do. Mutations are often just copying errors in the genome. If they prove harmful to the virus, it perishes. If they help the virus, then it continues to multiply, further establishing itself in a population. And if they help the virus to very easily infect vast numbers of people, then they can quickly lead to exponential growth.
That’s exactly what is happening right now. The virus from Wuhan ravaged the world like a smoldering fire, but the pandemic now more closely resembles a sea of flames raging across the globe.
German Chancellor Angela Merkel, who, as a physicist, has an in-depth understanding of numerical models, is deeply concerned about the current developments. In recent days, she has been calling ministers, scientists and experts she trusts, asking for suggestions about what to do if the new virus mutants also spread in Germany.
She doesn’t share the hope of some that the current lockdown can drive the numbers down any time soon. "Germany is facing eight to 10 very tough weeks,” Merkel said last Tuesday. The next day, during a meeting of her cabinet, Merkel discussed what would have happened had France not barred people from entering the country from Ireland. She said it might have become necessary for Germany to set up controls at the border with France.
Experts at the German Health Ministry are also concerned. "We are taking the emerging variants of the novel SARS-CoV-2 coronavirus very seriously,” a source in the ministry says. "The developments show that we now have to be even more vigilant.” The source said it is expected that more cases will emerge in Germany and that outbreaks will occur due to the new variant. "Initial studies suggest that this variant is even more easily transmissible and has an increased reproduction number."
RKI President Lothar Wieler came to a similar conclusion on Thursday. Responding to the new mutants, he warned: "There’s a possibility that the situation could get worse.
Europeans are especially worried about the mutant discovered in Britain because it is close, because there is so much contact between the island and the Continent.
But the B.1.351 variant discovered in South Africa and the B.1.1.248 mutant found in Brazil and Japan are no less harmful than their British cousin. On the contrary. They contain another mutation in their genetic material – E484K – which could prove to be very dangerous. It’s likely that it weakens the human immune response – and could even render some of the newly developed vaccines less effective. Pharmaceutical companies are currently testing the efficacy of their vaccines against the new mutants.
The mutation N501Y that is common to the new variants is located at a central position of the pathogen: on the spikes that are the source of the coronavirus’ name. SARS-CoV-2 uses the spike protein’s receptor binding domain to latch on to the host cell and invade it. Scientists believe the mutation makes it easier for the virus to latch on to host cells.
Once the new variants have infected the host, the disease proceeds just as it has in previous variants: They aren’t more lethal than the original coronaviruses. That, though, is hardly reassuring: Because the mutants are able to infect so many more people, they are capable of causing more fatalities than would a mutant that made people sicker but which was less contagious.
Adam Kucharski, a mathematician at the London School of Hygiene and Tropical Medicine has calculated the cruel logic of exponential growth: "An increase in something that grows exponentially," Kucharski explains, talking about the transmisson of the virus, "can have far more effect than the same proportional increase in something that just scales an outcome," like the severity of the illness the virus causes.
And physician Eric Topol of the Scripps Research Translational Institute in California wrote on Twitter: "If we wanted to get serious vs. B.1.1.7 … vaccinate 24/7 like it’s an emergency. Because it is.”
In places where the mutants begin spreading rapidly, they quickly displace their less contagious relatives, and right now the new variants are raging across Britain, South Africa and Brazil. In Ireland, the infection curve was pointing almost straight up. "Last year, there were dozens of different SARS-CoV-2 variants circulating here at the same time," reports bioinformatician and geneticist Tulio de Oliveira, who heads one of South Africa's largest sequencing labs at the University of KwaZulu-Natal in Durban. "Now, we're seeing that up to 90 percent of infections are with the new variant,” he says.
The crucial question is this: Can the mutants still be stopped – and if so, how? "There is a real risk that the more transmissible B.1.1.7 will overtake the existing variants and cause another wave before widespread vaccination," says Kevin Esvelt, director of the Sculpting Evolution group at the Massachusetts Institute of Technology.
The variant from Britain has long since taken root in Denmark, too. "It's really a game changer”, says Tyra Grove Krause, head of department at Denmark’s Staten Serum Institut. "It’s a whole different situation.”
Be it in Switzerland, the Netherlands or the United States – wherever viral genomes are now being sequenced, researchers are coming across traces of the English mutant. The B.1.351 variant from South Africa has already spread into neighboring Botswana, but the first cases have also been detected in Britain – as if one mutant were now competing against the other.
A variant of the coronavirus from Brazil also popped up in Japan in early January. Evidence is also mounting that the Brazilian and South African mutants can infect people who have already had COVID-19.
That would mean that there is either no immunity to the new variants, or that such immunity is weak. Future research will have to determine whether that is the case. No one knows yet what the implications of the mutations are.
What we do know, though, is that the combination of the one common mutation together with certain other changes in the genome has produced variants that are highly contagious. Is this the coronavirus of the future? Will each variant now mutate in ways to make it more contagious, creating deadly perfection?
"I think that the virus is just finding its optimal configuration”, says Cillian De Gascun, director of the National Virus Reference Laboratory at University College Dublin. That the same mutation occurred in all the variants independently of each other suggests "that this is a configuration that the virus likes,” says De Gascun. "And there's no reason to believe that it won't become more efficient over time.”
Experiments are now underway at major biomedical laboratories in South Africa, as well as at vaccine manufacturers, to determine whether the biggest worry of all is justified: that the vaccines will be less effective against the various new variants. Those experiments include exposing the virus to the blood serum of vaccinated patients.
If the virus survives, then humanity has a big problem.
"What we’re dealing with now is a new pandemic," says epidemiologist Kucharski. It could turn out that what we have learned so far and the methods that have been used to combat the disease are no longer valid. Against that backdrop, the researcher recommends that new variants be treated "as a new threat, not thinking, 'well, we've already got lots of COVID cases, so this is just a bit more of the same problem'."
But how is it that such malignant new variants of the virus emerged so suddenly and simultaneously? As epidemiologist Emma Hodcroft from the Institute of Social and Preventive Medicine at the University of Bern explains, the common mutation has already occurred several times in the various coronavirus variants whose genetic material was examined last year – and remained inconspicuous.
"It is likely," the British-American scientist explains, "that it is a combination of different mutations plus N501Y that really changes the virus and makes it more transmissible."
In the year since the virus was discovered, a race has been on between SARS-CoV-2 and the human immune system. The virus, initially unrecognizable to the body’s defenses, infects cells, thus triggering a response from the immune system, which learns about the enemy – its receptor binding domain, for example – and develops antibodies that bind to the virus and take it out of commission. When SARS-CoV-2 attacks humans again, they already have antibodies. The virus is intercepted and no longer has a chance.
But it turns out that an incidental change in the genetic material provides a considerable advantage to the intruder: The mutation alters the point of recognition for human antibodies, thus making the virus more difficult for the immune system to detect. This means that the human body is forced to start almost from scratch when building up a defense.
Many virologists don’t believe it to be a coincidence that these kinds of mutations have arisen in parts of the world that had problems controlling the first wave of the virus – areas like the Eastern Cape of South Africa and Manaus in Brazil, places with poor health care and considerable poverty. "In areas where lots of people have already been infected, the original coronavirus may not have been able to reinfect them," explains Hodcroft, who calls herself a "virus hunter" on Twitter. "In those areas the virus has a lot to gain with a mutation that enables it to do so.”
In Germany, where the first wave was mild, SARS-CoV-2 would be less likely to mutate in that way. But in other places, viral evolution took place in fast-forward.
Given the speed, Tulio de Oliveira, the genetics professor from South Africa, believes that similar mutants have evolved in other places. "I wouldn’t be surprised if this kind of variants keep emerging in countries that haven’t gotten the pandemic under control for a long time,” he says. "Places like the U.S., for example, or Russia, but also Spain or Italy."
Meanwhile, mutants that are perfectly adapted to the host can also arise when a pathogen is able to persist and multiply for a long time in the body of a patient whose immune system is compromised – as a result of chemotherapy or radiation therapy, for example. "And so the virus has a really long time to figure out how to co-exist with the human immune system," explains Emma Hodcroft. "It's got all the tipps and tricks for living within humans." The mutants that survive and continue to reproduce are those that are particularly adept at deceiving the immune system.
If you had asked her a few months ago how likely it was that dangerous SARS-CoV-2 mutants would be created in this way and spread through the population, Hodcraft says, she would have replied that, "this probably isn't one of our biggest concerns" right now. "But when we have so many people infected, we allow the virus to get into these unique, weird scenarios. We are providing it with a playground.”
De Oliveira’s discovery of the South African variant earned him a bottle of wine, but he’s not exactly proud of it. He’s still fond of sharing how he got it because the anecdote casts light on what is so important to him and all scientists working in the fight against the disease right now: It illustrates how tremendously well they work together, across time zones and countries.
De Oliveira, a Brazilian-South African researcher, was alerted to the variant by clinicians and hospital workers in the Eastern Cape province. "They noticed that the second wave was coming much faster than the first,” he reports. "It struck them as being odd.” They contacted him and sent samples, which de Oliveira and his team then sequenced. They got the results on Dec. 1.
"We were shocked,” says de Oliveira. He’s sitting in his office in the modern laboratory building in Durban. With his bright, short-sleeved shirt and ponytail, he looks more like a surfer than a genetics professor. "In all 11 samples, which came from the same source, we found the same virus, and that was unusual,” he says. More importantly, the find was different from the previously known variants: Oliveira and his team were able to identify 23 mutations, including N501Y and E484K.
Oliveira felt it was time to sound the alarm. He informed his boss and then immediately contacted the World Health Organization (WHO).
He won the bottle of wine because when he asked Stellenbosch university virologist Susan Engelbrecht if she could test her samples from early December for the mutation, he also made a bet with her that it would be found in more than half the samples. She thought it was out of the question given that Stellenbosch is located a full 700 kilometers away from the local outbreak that had taken place in Eastern Cape. "She then texted me in the middle of the night: 'Oh God, I lost my bet.’”
But de Oliveira won’t get the bottle of wine until the virus is contained, because South Africa has not only cleared beaches and banned parties in the lockdown, but also banned alcohol.
Oliveira then contacted Andrew Rambaut, a colleague in Edinburgh, Scotland, on Dec. 1, and asked him to take a look at his strange findings. A few days later, de Oliveira received an email from Rambaut. In it, Rambaut reported a similar disturbing finding in the UK. They had also detected the presence of the N501Y mutation, but in a different variant of the virus. On Dec. 19, Rambaut published a paper about the new English variant of COVID-19. Rambaut would later tweet that de Oliveira had given him the idea to look for N501Y.
The damage that a more contagious variant can do – in this case B.1.1.7 – is on full display in Britain at the moment. "What I hope is that we've given a warning to the rest of the world that this is a serious problem”, says Jeffrey Barrett from the Wellcome Sanger Institute in Cambridge, where the genetic material of several thousand positive virus samples is sequenced and analyzed every week.
The third report from Public Health England, which Barrett worked on, shows how quickly B.1.1.7 has spread in Britain. The first known time the variant was detected was in a sample dating back to Sept. 20. Around mid-November, its share of COVID-19 infections increased significantly. Just before Christmas, around 60 percent of all new coronavirus cases in London were attributable to B.1.1.7, thus ending the holidays for Barrett.
Despite the immediate imposition of a strict lockdown, the number of infections still skyrocketed, with Johns Hopkins University reporting over 60,000 new infections a day on multiple occasions. The share of the B.1.1.7 variant in London and the southeast of England has now risen significantly again and is in the process of spreading across the entire country.
"We saw it probably as quickly as any country could have seen it”, says Barrett. But B.1.1.7 was already too widespread. "So it was impossible to slow down.” The situation in the country has taken a very dramatic turn. Doctors are even speaking of war-like conditions in some of the hopelessly overcrowded hospitals.
In Britain, it has become abundantly clear that a half-hearted lockdown was not enough to combat the new mutant. In November, at a time when there were some restrictions, but schools remained open and many people continued to go to work as normal, B.1.1.7 was able to spread deeper into the population.
Only now, with a strict lockdown in place, have case numbers started to fall, but much more slowly than with the old variants.
"I know people are exhausted, everyone in the world is exhausted,” says Barrett. "But I would recommend Germany to try to introduce restrictions or strengthen restrictions to bring case numbers down as much as feasibly possible.”
Merkel's Chancellery also believes that it is urgently necessary to keep tough measures in place or even to intensify them – for as long as it takes to reduce the 7-day incidence rate back down to 50 cases per 100,000 people so that health officials can resume tracking individual cases and breaking infection chains through quarantine measures.
But will people continue to accept corona restrictions once numbers sink again? And more importantly: Will Germany's governors, many of whom have continually been slow to recognize the threat and who ultimately have the power over implementing many of them, go along with even stricter measures?
Even in spring, tendencies emerged that Merkel viewed with mistrust. In April, the chancellor railed against the growing tendency among state leaders to focus their attentions on reopening the economy rather than on controlling the virus. Now, she is concerned that, with numbers slowly falling, she won't be able to resist public pressure to begin loosening one measure after the next, thus triggering a disastrous domino effect. That, she fears, would quickly drive numbers up again.
Already, in fact, some states are no longer adhering to the measures agreed to in the Jan. 5 meeting between Merkel and the state governors. In North Rhine-Westphalia, for example, Governor Armin Laschet, who was elected chairman of the center-right Christian Democratic Union (CDU) party on Sunday, never fulfilled his pledge to strictly implement all of the measures. In the state's rules, measures limiting social contacts only apply to public spaces and not to private living quarters. In homes, only parties were forbidden.
In the city-state of Bremen, meanwhile, state leader Andreas Bovenschulte unilaterally introduced a program to test schoolchildren in an effort to keep schools open. In Hesse, measures for limiting contacts in private living spaces are merely recommendations and not rules. And Lower Saxony even reopened elementary schools on Monday.
States under the leadership of the center-left Social Democratic Party (SPD) have been particularly skeptical of Merkel's warning. The chancellor, according to a source in one SPD-run state capital, is apparently trying to prepare the populace for an extension of the lockdown until Easter.
To see what can happen if coronavirus measures are loosened as the new mutant is spreading, all you have to do is look at Ireland, where case numbers rocketed upward after Christmas. The few sequencing results from Ireland show that while less than 10 percent of positive tests at Christmas were caused by B.1.1.7, that share had risen to 45 percent by the middle of January.
Patrick Mallon is a professor of microbial diseases in the University College Dublin School of Medicine and a consultant in infectious diseases at St Vincent’s University Hospital in Dublin. He looks tired, having just finished treating patients. For our Zoom interview, he takes off his mask. "My normal work is supposed to be 50 percent working in clinical infectious diseases and the other 50 percent, I am supposed to be working in research. At the moment, it's very difficult for me to do anything other than clinical work."
Four of the hospital’s wards are fully committed to care for COVID-19 patients at the moment. "And we are admitting probably between another half and one full ward per day,” says Mallon. Doctors are trying to get enough people discharged from hospitals. "But unfortunately, the people that are coming are very sick and require long hospital admissions. So it's a very worrying set of numbers.”
For a long time, it looked as though Ireland would get through the pandemic relatively unscathed. But the country also never tried to push case numbers down to zero in the way that both Australia and New Zealand did, instead hoping to be able to manage the pandemic to the degree possible. But then, corona measures were loosened in December, triggering the current calamity.
On Dec. 23, B.1.1.7 was detected for the first time in Ireland. "It was right before Christmas and we didn't feel the variant was a concern at that point in time," recalls National Virus Reference Laboratory Director De Gascun. "But at that stage, in many respects, I sense that the damage was done."
Many in Ireland celebrated Christmas with their families, driving across the country to do so. "It was the perfect storm," says Mary Horgan, physician, expert in infectious diseases and president of the Royal College of Physicians of Ireland.
Mallon believes that it was a mistake to allow case numbers to simmer at a low level rather than try to stamp out the virus. "I think that what we're experiencing is the inevitable outcome of that strategy,” he says. "I think that this is a lesson that governments around Europe should learn. What is happening in Ireland shows just how vulnerable countries are that are trying to live with the virus – and that it's becoming increasingly more difficult to do that dealing with the new variant of the virus. What's happened in Ireland really just shows you how unpredictable this virus is.”
In Germany, Federal Health Minister Jens Spahn already finds himself confronted with accusations that he acted too late. Carsten Schneider, deputy floor leader for the SPD in parliament, referred to it on Wednesday as a "race against time for human life."
Last Monday, Spahn introduced two draft regulations designed to impede the spread of the new virus variants. The first one requires travelers from countries where the mutants are circulating to present a negative coronavirus test before being allowed to enter Germany. Airlines are to demand the tests during check-in. In general, those returning from risk areas will have to prove within 48 hours that they are not infected with SARS-CoV-2. "Trips abroad to risk areas are inconsistent with the pandemic situation," Spahn said.
With the second regulation, Spahn wants to ensure that Germany finally begins systematically searching for mutations in the virus genome. The goal is "the rapid detection of virus variants whose mutations represent a particular threat," he said – those that spread more quickly, trigger more severe symptoms or do not respond as well to vaccination or previous infection.
Specifically, the regulation would require laboratories and hospitals to sequence 5 percent of all PCR tests and send the results to RKI. Once the number of new infections is pushed below 140,000 in two weeks, up to 10 percent of the tests could be sequenced.
With laboratories already complaining about a lack of capacity, the regulation comes with a monetary incentive: For each test sequenced and reported to RKI, laboratories will receive 200 euros. The federal government in Berlin has earmarked a budget of 200 million euros for the program.
Thus far, RKI says it only has data from the sequencing of 3,000 virus genomes – far less than Denmark and the UK. In the future, RKI is to receive anonymized results that include the patient's age, gender, the first three numbers of their postal code and the date on which the sample was taken.
Christian Drosten, head virologist at Berlin's Charité University Hospital and the leading German expert on the coronavirus, supports "establishing a direct link between routine laboratory testing and RKI." That, he says, "is surely the most efficient way to collect a relatively large number of sequences in a short time while integrating the important reporting data." Without that information, sequencing would be a lot less valuable, Drosten told DER SPIEGEL.
But he also calls on diagnostic laboratories to avoid "depending entirely on the sequencing." It takes quite a lot of time, he notes, particularly given that such analyses are generally only performed every few days after gathering a number of samples.
Drosten has a pragmatic alternative in mind: the implementation of a mutation PCR. Essentially, the idea is a PCR test that only identifies the N501Y mutation. "If that test comes back positive," the virologist says, "then we can start testing for other mutations."
It is a strategy for slowly closing in on the culprit. Is it from South Africa, England or Brazil? The diagnosis is then to be reported to the sender as quickly as possible "so that contact tracing can begin without delay."
Public health departments also have to gear up for the new mutants as quickly as possible, and RKI has revised its recommendations to help make that happen. Should there be indications or a suspicion that a new infection has been caused by a new variant, contact tracing for that case should be prioritized. The top priority is that of "preventing infection chains from the new mutant," says an RKI spokeswoman.
Thus far, contacts have been allowed to cut short their quarantine period if they could present a negative test after 10 days. But that will now change. According to the new RKI recommendations: "In cases in which the infection is proven to have come from a new variant of SARS-CoV-2, as initially isolated in England and South Africa, no reduction of the 14-day quarantine should be allowed."
Merkel's cabinet is also examining new measures: Do border controls have to be reintroduced to protect against the mutants? Should the federal government withdraw the right of states to draw up their own measures, a move that would require parliamentary approval? Should there be a nationwide requirement that FFP2 masks be worn as is currently the case in Bavaria, or would that give people a false sense of security? Is a regulation necessary to force employers to allow more of their staff to work from home? Should the number of passengers in buses and subways be limited, or should public transportation systems be shut down entirely?
That last question was apparently submitted to the Transport Ministry, but officials there voiced concern that such a step could interrupt supply lines. The chancellor also ultimately voiced her opposition to the measure.
Denmark could offer a blueprint for dealing with the mutants. The country had already been shaken by another new virus variant that had appeared in minks, but which could be passed to humans. Then, in mid-December, the country discovered its first cases of the British mutant B.1.1.7. The government reacted quickly and decisively.
"We found out very quickly that only some of the cases had epidemiological links to the U.K., so there were signs of community transmission already at this early stage,” says Tyra Grove Krause of Denmark’s Staten Serum Institut. Since then, the fight against B.1.1.7 has had top priority. "In this month, we're going to genome sequence every single positive sample,” says Krause.
The new variant climbed from representing 0.3 percent of all samples sequenced in November to 2.9 percent in early January. The number may seem low, but Krause is far from comforted. The mutant's share of total cases is growing exponentially. "We expect that B.1.1.7 will be the dominant variant in Denmark when we reach mid-February."
Denmark has been in lockdown since Dec. 11 and case numbers are dropping. The reproduction number, which refers to the average number of people to whom an infected person passes the virus, is now at 0.9. But Krause doesn't find that particularly reassuring either. "We think this is like the calm before the storm. We need to have a reproduction number below 0.7 if we want to avoid exponential growth in February and March."
Ultimately, it will be a race against time. Vaccinations have begun in Denmark, as well, and once the weather begins warming up in summer, there is hope that infection numbers will drop again. Until then, though, all efforts will be focused on delaying the spread of the new variant to the degree possible, says Krause. "So, the strategy now is to really get the case numbers down throughout January so that we have a low case count when this new variant starts to take over.”
It isn't easy, Krause says, to explain to the population why it is so important right now to maintain the lockdown even as case numbers are sinking. "But what can you do? The threat is just around the corner."