9 May 2021

Countries That Let the Virus Run Rampant Are a Danger To Everyone

By Marian Blasberg, Rafaela von Bredow, Veronika Hackenbroch, Kunal Purohit und Christoph Schult

COVID-19 patients in the emergency department of a New Delhi hospital: India has reported 315,000 new infections in a single day, more than ever before. 

No one knows if Mumtaz Shaikh will survive. He’s 48 years old, not the typical age of someone who dies from COVID-19. But SARS-CoV-2 is raging in India like never before – including in the megacity of Mumbai. The clothing seller is among the many who have been infected.

Shaikh is one of thousands of COVID-19 patients across India whose lives are in danger. It’s almost impossible for them to find help because SARS-CoV-2 has swept across the country with such force that the already underfunded health care system is on the verge of collapse. When Shaikh was admitted a week ago Thursday for respiratory distress, the hospital had run out of oxygen to put him on a ventilator.

The hospital called at 2 a.m. Shaikh’s wife Shahnaz and a cousin, Sidrah Patel, who had gone to the hospital with her, couldn’t believe it. They were told to find oxygen for Shaikh themselves, but it was in short supply everywhere. Only three days earlier, 11 people died in another Mumbai suburb, reportedly because doctors could no longer ventilate them. The two women called around. "After over an hour, someone suggested a local politician,” Patel says. "He then agreed to lend us an oxygen cylinder.”

When they brought the cylinder to the clinic in the morning, the doctors said they were now out of an antiviral drug, as well. Without it, Shaikh wouldn't have a chance.

His wife and cousin set out to find it. Shady dealers offered them two doses of the drug at astronomical prices. They had to borrow money from friends, and the next night they were directed to go to a school about 42 kilometers (26 miles) away, but by the time they arrived, the line was so long that they couldn’t get any more.

In the end, they found what they were looking for on the black market and the drug was only twice the normal price. But a week has passed and Mumtaz Shaikh still isn’t doing any better. His condition has actually worsened. By Thursday night, his oxygen saturation had dropped to 60 percent.

The same day, India reported a sad world record: around 315,000 new coronavirus infections in a single day. The United States didn’t even reach that level when it hit its peak of infections in January. Within 24 hours, more than 2,100 people died from COVID-19. In New Delhi, the highest court reprimanded the government for the shortage of medical oxygen. There is also a lack of ventilators and hospital beds. Sick people and their relatives are lining up in front of the hospitals and pharmacies. The crematoria are running extra shifts to keep up with demand.

And the curve in India continues to rise rapidly, with 1.6 million new infections in the past week. There is no end in sight either, in a country where only 1.3 percent of the population has been fully vaccinated.

Indian Prime Minister Narendra Modi, who is drawing the ire of many Indians for underestimating the pandemic and not foreseeing the coming disaster, said last week that his country had been "hit by a storm” with the virus.

"There is virtually no one left in India who doesn't know someone who is infected with COVID, some severely,” says Gautam Menon, a professor of biology and physics at Ashoka University in Sonipat, which is located near the capital city of New Delhi. "Our model projections for the next few weeks suggest that cases will continue to increase." The situation may only start to improve in mid to late May, he says. "What the state of our country will be then is anyone's guess."

What has the Indians – and the world – terrified is a viral mutant that is spreading rapidly through the country. Its scientific name is B.1.617. The new virus has already been detected 21 times in Germany. In Britain, the number of people infected with B.1.617 rose from 77 to 132 within a week.

It is potentially made dangerous by its mix of two mutations – although it still unclear whether and how exactly they affect the infection process. The two genetic alterations, E484Q and L452R, could make it easier for the virus to dock and enter the cells in the nose and throat of its hosts. That would make the pathogen more contagious.

They could also enable the virus to partially escape the immune defenses of its hosts. Alex Sigal, who heads an offshoot of the Berlin-based Max Planck Institute for Infection Biology in Durban, South Africa, believes the two mutations "would almost certainly cooperate” to increase escape from the host’s defenses.

He is referring to the antibodies the body forms when people are infected with SARS-CoV-2 that would normally mark the virus in the event of a reinfection so that immune cells can destroy it. But the mutation changes the signal, making it impossible for important antibodies to recognize the pathogen. Variants that succeed in this are known as escape mutants.

And that’s the horror scenario: that B.1.617 could actually escape the immunity built up by vaccines in the bodies of vaccinated people. If that happened, we would be dealing with a new pandemic and we would be right back at square one.

B.1.1.7, the British variant, is showing the havoc a more contagious virus variant can wreak. And the P.1 variant in Brazil shows that a mutant capable of tricking the immune system can infect people who already had COVID. In the second wave, scientists suspect that up to 61 percent of all the coronavirus cases there stemmed from such re-infections in the city of Manaus. More than 380,000 Brazilians have died as a result of COVID-19 so far.

Unfortunately, a scenario the British epidemic expert Jeremy Farrar predicted in an interview with DER SPIEGEL at the end of last year, appears to be coming to pass. He said at the time it was "inevitable that these new variants will spread and soon become dominant around the world.” He added, "It could get worse if the virus continues to change.”

"We need to vaccinate the whole world – for all our self-protection"

Farrar, who is the director of the Wellcome Trust, one of the world’s largest foundations funding medical research, now fears the virus will continue to mutate. "We can’t predict which variants will emerge, but we know they will come,” he says.

What is currently happening in India and Brazil is a kind of field experiment – a gigantic and tragic one. "If you're trying to figure out the best way to breed new variants that knock out immune protection," Farrar says, "you would let the pandemic expand and let the virus infect such large populations." The only way to prevent this is to contain the spread of the virus and build immunity worldwide through vaccination. "We need to vaccinate the whole world, for scientific, public health and economic reasons as well as for moral reasons – and for all our self-protection."

In India and Brazil, politicians and officials have violated an iron rule of pandemic management: "Hit hard and early " to contain the pathogen. Those who wait to see if things will really get as bad as the virologists and epidemiologists have predicted have already lost the battle.

The Indian mutant was first discovered in January in an analysis of three samples from the state of Maharashtra. More cases quickly followed. In late March, virologist Shahid Jameel expressed suspicion "there may be a separate lineage developing in India.”

Jameel had planned to report in detail to DER SPIEGEL his assessment of the danger posed by the mutant, then SARS-CoV-2 struck in his own family. With several COVID victims in his circle of friends and acquaintances, he asked to be excused, noticeably shaken.

It’s still unclear to what extent B.1.617 is fueling India’s outbreak. "India isn’t sequencing enough right now,” says Menon, the biologist, "more data is urgently required." But, he adds, "we know from the state of Maharashtra that the variant had a share of 20 percent in March that has now risen to 60 percent.” In Delhi and Punjab state, the UK variant is implicated in the rise of cases, with another indigenous variant seeming to be more prevalent in South India.

In any case, virologists know only theoretically what a mutation’s effect is, both biologically and infection-wise. Laboratory experiments are required to determine whether a mutant virus can really escape the immune defenses – or render vaccines virtually ineffective, as researchers have recently demonstrated can occur with the South African mutant B.1.351 and AstraZeneca’s vaccine. An experiment in the country comparing people who had been vaccinated and people had been injected with a placebo showed that those who had received vaccines displayed only slightly fewer cases of infection with the variant.

This raises several questions: Is the Indian double mutant actually more contagious? And does it lead to more severe disease? Can it dodge immune defenses the way P.1 from Brazil does?

Gautum says the variant is spreading "much more rapidly” than the original virus. Doctors are also seeing entire families getting infected all the time. And there are increasing reports of new symptoms, including conjunctivitis and diarrhea with fever. But is the double mutant making people sicker? Menon says we don’t know that yet. The science magazine Nature headlined its article on Wednesday about the India situation with, "India’s massive COVID surge puzzles scientists.”
Bild vergrößern

The graves of the coronavirus dead in São Paulo: Brazil has been hit by a vicious variant of the coronavirus. Foto: Miguel Schincariol / afp

Menon says there is limited evidence, mainly anecdotal at this point, that people are getting reinfected by the new variant, which could indicate an escape mutant. There have been reports of cases even in vaccinated people, he says, but that is to be expected in a large outbreak like this.

"Without doing the experiments, we can't be sure,” says Max Planck researcher Sigal. But "some reduction” in the effectiveness is to be expected, he says, and AstraZeneca’s vaccine is more vulnerable since it induces lower levels of neutralizing antibodies in those vaccinated with it.

If a new mutant emerges, it has the potential to change the situation globally within a matter of weeks. "The new variants are changing the course of the pandemic,” Farrar says.

In Germany, measures that would have successfully lowered the infection rate six months ago are now failing to contain the British variant, B.1.1.7. In Britain, almost as many people have died from COVID-19 since Christmas, when the variant began to run rampant, as died in the rest of 2020.

And Brazil provides a good example of what an escape mutant can do.

Felipe Gomes Naveca, who heads the research department at the Fiocruz Institute in Manaus, still remembers sitting in his lab in January sequencing a sample from a patient who had contracted COVID-19 for the second time. Naveca was amazed. His finding coincided with what colleagues from Japan had found in four Japanese tourists who had returned from the Amazon: P.1., a new virus mutant.

P.1 has a total of 17 mutations, 10 of which affect the spike protein with which the virus attaches to the host cell. These include the E484K mutation, which partly helps it evade the immune system.

This helps to explain how the country has now been hit a second time.

Last spring, Manaus became the first large city in Brazil to see its hospitals collapse under the pressure of the coronavirus. The first wave was so powerful that researchers at London’s Imperial College suspected in September that herd immunity may already have been reached there. But a short time later, the number of cases rose again suddenly. In January, Naveca says, the curve was almost vertical. Patients were lying in the corridors of hospitals. They were young people – and this was largely the result of P.1.

Studies suggest that the mutant is much more contagious than the original coronavirus. Naveca says the viral load is up to 10 times higher compared to other variants. In addition, the mutations in the modified pathogen make it easier for it to dock onto human cells and partially evade the immune defense system. The good news is that the first laboratory experiments have shown that the effectiveness of the vaccines is only slightly weakened.

Within the span of only a few weeks, P.1 dominated infection patterns in a dozen Brazilian states. Scenes like the ones coming out of Manaus were repeated in the megacities of Rio de Janeiro and São Paulo.

Miguel Nicolelis, a Brazilian doctor and professor at Duke University recently went so far as to describe his homeland as being on its way to becoming a "biological Fukushima.” Like many of his colleagues, he fears that with the virus circulating unrestrained within the population, it could mutate into a new and even deadlier variant that could undo the world’s efforts to control SARS-Cov-2 overnight.

Brazilian President Jair Bolsonaro has done everything possible since the beginning of the pandemic to ensure that Brazil becomes a breeding ground for super mutants – almost as if he is an ally of the virus. He played COVID-19 down like it was a harmless flu and encouraged people to go on with their daily lives to keep the economy going.

He disparaged mask-wearers as "faggots” and invested millions in a malaria drug called chloroquine, which he touted as a miracle cure even though, in some cases, it increased the mortality rate. And when the rest of the world began stockpiling vaccines, he claimed that the best protection from COVID-19 was to contract the disease and recover from it. During the coming weeks, an investigative committee in the Brazilian Senate will determine how much responsibility the Bolsonaro government bears for the deadly disaster.

P.1 has long since ceased to be just a Brazilian problem – the mutant has been detected in numerous other countries. In Germany, its share in overall infections has been constant at around 0.1 percent for several weeks now. But it is starting to spread elsewhere, especially in Canada where the vaccination campaign has been slow and, like Germany, B.1.1.7 is still dominant.

The virus found ideal conditions at the Whistler ski resort in western Canada, in the cramped communal housing for the mostly young and international seasonal ski-industry workers. P.1 quickly spread from there to nearby Vancouver, where the pathogen infected more than 20 players with the Vancouver Canucks hockey team, some of whom, even though young and in very good physical condition, unexpectedly became quite ill.

Now, P.1 is spreading further and further to the east in Canada. "A few weeks ago, we only had a handful of cases in the state of Alberta, now we have over 180,” reports Matthias Götte, a professor of medical biology and immunology at the University of Alberta at Edmonton, which is located about 800 kilometers from Vancouver. Schools have been closed again there since Thursday. "Of course, we don’t know what is going to happen now,” says Götte. "But the illnesses with the Vancouver Canucks have shown people here how dangerous P.1 can be.”

Is there a chance that P.1 will eventually gain a real foothold in Germany? Or will B.1.617, the Indian variant, replace B.1.1.7 in our country -- perhaps after coming in through the UK? These are completely open questions.

"The variant belongs to the group of lines that we currently have under observation,” an official from the Robert Koch Institute, Germany’s center for disease control, wrote to DER SPIEGEL in response to a request for comment. "In our assessment, there is currently no corresponding evidence to warrant classifying it as 'worrying’.”

Given the rapidly rising number of infections and the virus mutation, German has largely banned travel to the country from India. "To prevent jeopardizing our vaccination campaign, travel to India must be significantly restricted,” German Health Minister Jens Spahn of the conservative Christian Democratic Union tweeted earlier this month.

The German government declared India a virus variant area on Monday, a move that Berlin initially shied away from. One reason for that reserve, DER SPIEGEL has learned from sources, is that passenger planes have increasingly been transporting goods in the cargo holds since the beginning of the pandemic. Given the India is one of the main producing countries for vaccine components, a transport ban would also hamper supplies for vaccine production.

"We now know more about the virus variants than we did five months ago when B.1.1.7 was discovered,” says Jeff Barrett, director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute in Cambridge, England. "But it’s still difficult to make predictions.”

It is quite conceivable that, as more and more people are vaccinated, the South African variant, B.1.351, which currently has a share of 0.7 percent of infections, will spread here. Jörg Timm, director of the Institute of Virology at the University Hospital of Düsseldorf, believes that this scenario is possible.

Any country that allows the virus to run rampant is breeding the next super mutant.

"The variant that will prevail in the end depends on many factors,” he says. "I’m sure chance plays a role in that, too.” Right now, B.1.351 is the most widespread of the variants of concern in Germany. "If the selection pressure increases due to vaccination, it would initially have an advantage, simply because it is already here,” says Timm.

Every country that allows the virus to run rampant is breeding the next super mutant or the one after that – and at some point there may be a mutant against which no vaccine can help. Jeremy Farrar says that there may be "only a low chance, perhaps less than 10 percent,” that a dreaded variant like that would emerge that would take us back to zero. "But 10 percent is far too big a risk to take.”

Clearly, the better option would be to go as far as possible to eliminate that risk. "We can reduce the 10 percent to 1 percent or less if we push back the infection and build immunity worldwide," Farrar says. His message is as clear as it is simple: Lockdowns to reduce transmission – and non-stop vaccination campaigns.

No comments: