Within a few weeks, two variants of the coronavirus became so well-known that you often hear their unfathomable alphanumeric names pronounced on television news.
B.1.1.7, first identified in Britain, showed the power to spread rapidly and rapidly. In South Africa, a mutant called B.1.351 can evade human antibodies and blunt the effectiveness of some vaccines.
Scientists also mentioned a third about the variant that originated in Brazil, P.1. Research has been slower on P.1 since it was discovered at the end of December, and scientists are uncertain how much to worry about.
“I held my breath,” said Bronwyn MacInnis, an epidemiologist at the Broad Institute.
Three studies now provide a sobering history of the meteoric rise of P.1 in the Amazon city of Manaus. It probably originated there in November and then fueled a record increase in cases of coronavirus. It dominated the city, in part due to increased contagion, the research found.
But it also gained the ability to infect some people who had immunity to the previous attacks of Covid-19. And laboratory experiments suggest that P.1 may weaken the protective effect of a Chinese vaccine now used in Brazil.
The new studies have yet to be published in scientific journals. Their authors warn that findings about cells in laboratories do not always translate into the real world, and that they have only begun to understand P.1’s behavior.
“The findings apply to Manaus, but I do not know if they apply elsewhere,” said Nuno Faria, a virologist at Imperial College London, who led much of the new research.
But even with the riddles remaining around P.1, experts have said it is a variant to take seriously. “It’s right to worry about P.1, and this data gives us the reason why,” said William Hanage, an epidemiologist at the Harvard TH Chan School of Public Health.
P.1 now spreads over the rest of Brazil and is found in 24 other countries. In the United States, the Centers for Disease Control and Prevention reported six cases in five states: Alaska, Florida, Maryland, Minnesota, and Oklahoma.
To reduce the risks of P.1 outbreaks and re-infections, dr. Faria said it is important to double each size to slow down the spread of the coronavirus. Masks and social distance can work at P.1. And vaccination can help reduce its transmission and protect those who become infected from serious diseases.
“The ultimate message is that you need to increase all vaccination efforts as quickly as possible,” he said. “You have to be one step ahead of the virus.”
Dr Faria and his colleagues started tracking the coronavirus when it exploded in Brazil last year. Manaus, a city of two million in the Brazilian Amazon, was particularly hard hit. During his spring, Manaus’ cemeteries were overwhelmed by the corpses of the dead.
But after a peak at the end of April, Manaus seemed to have overcome the worst pandemic. Some scientists thought that the decline meant that Manaus gained herd immunity.
Dr Faria and his colleagues searched for coronavirus antibodies in samples from a Manaus blood bank in June and October. They found that about three-quarters of the inhabitants of Manaus were infected.
But by the end of 2020, new business began to increase again. “There were actually a lot more cases than in the previous peak of cases, which was the end of April,” Dr Faria said. “And it was very mysterious to us.”
To look for variants, dr. Faria and his colleagues begin a new attempt at sequencing genomes in the city. While B.1.1.7 arrived in other parts of Brazil, they did not find it in Manaus. Instead, they found a variant that no one had seen before.
Many variants in their samples shared a set of 21 mutations not seen in other viruses circulating in Brazil. Dr Faria sent a text message to a colleague: “I think I’m really watching something strange, and I’m quite worried about it.”
Some mutations in particular worried him, because scientists had already found them in B.1.1.7 or B.1.351. Experiments have suggested that some of the mutations would better enable the variants to infect cells. With other mutations, they can evade antibodies from previous infections or through vaccines.
While dr. Faria and his colleagues analyzing their results, researchers in Japan made a similar discovery. Four tourists who returned on January 4 from a trip to the Amazon were positive for the coronavirus. Genome sequencing revealed the same set of mutations that Dr. Faria and his colleagues saw in Brazil.
On January 12, Dr. Faria and his colleagues posted a description of P.1 on an online virology forum. They then investigated why P.1 was so common. Its mutations may have made it more contagious, or it was lucky. With a mere chance, the variant would possibly have appeared in Manaus, just as the city becomes more relaxed about public health measures.
It was also possible that P.1 became common because it could re-infect humans. Normally, coronavirus re-infections are rare because the antibodies that the body produces after infection are strong for months. But it was possible that P.1 had mutations that could make the antibodies harder on it, allowing it to slip into cells and cause new infections.
The researchers tested these possibilities by detecting P.1 from the earliest samples in December. At the beginning of January, it made up 87 percent of the samples. By February, it had completely taken over.
By combining the data of genomes, antibodies and medical records in Manaus, the researchers concluded that P.1 conquered the city, not thanks to luck, but also through biology: the mutations helped spread it. Like B.1.1.7, it can infect more people on average than other variants can do. They estimate that it is somewhere between 1.4 and 2.2 times more transmissible than other lines of coronaviruses.
But it also gets a lead of mutations that cause the antibodies of other coronaviruses to escape. They estimate that in 100 people infected in Manaus last year, somewhere between 25 and 61 of them may have been re-infected by P.1.
The researchers found support for this conclusion in an experiment in which they mixed P.1 viruses with antibodies from Brazilians who had Covid-19 last year. They found that the effectiveness of their antibodies decreased sixfold compared to P.1 compared to other coronaviruses. That drop could mean that at least some people would be vulnerable to new infections from P.1.
“There seems to be an increasing body of evidence to suggest that most cases associated with the second wave are indeed types of reinfections,” Dr Faria said.
Dr Faria and other researchers are now looking at Brazil to observe the distribution of P.1. Dr. Ester Sabino, an expert in infectious diseases at the University of São Paulo School of Medicine, said that one of the new outbreaks in Araraquara, a Brazilian city of 223,000 people, has arisen that does not have a high dose of Covid -19 before P.1. arrived.
If people in Araraquara did not have a high level of antibodies before the arrival of P.1, she said, suggesting that the variant could possibly spread to places without the extreme history of Manaus. “It can happen anywhere else,” she said.
Michael Worobey, a virologist at the University of Arizona who was not involved in the research, said it was time to pay attention to P.1 in the United States. He expected it to become more common in the United States, although it would have to compete with B.1.1.7, which would soon become the predominant variant in much of the country.
“At least it’s going to be one of the candidates,” said Dr. Worobey said.
In their experiments, dr. Faria and his colleagues also tested antibodies from eight people who received CoronaVac, a vaccine manufactured in China and Brazil. They found that the vaccine-generated antibody bodies were less effective at stopping the P.1 variant than other species.
Dr Faria warns that these results, derived from cells in test tubes, do not necessarily mean that vaccines will be less effective in protecting real people against P.1. Vaccines can protect very well against P.1, even if the antibodies they generate are not as strong. And even if the variant succeeds in infecting vaccines, they are likely to be protected from a severe attack on Covid-19.
For dr. Sabino is the utmost importance of P.1 the threat that variants pose when they can emerge anywhere in the world.
“It’s just a matter of time and chance,” she said.