In just a few weeks, two variants of the coronavirus have become so familiar that you can hear their inscrutable alphanumeric names regularly spelled out on television news.
B.1.1.7, first identified in Britain, demonstrated the power to spread quickly. In South Africa, a mutant called B.1.351 can evade human antibodies, decreasing the effectiveness of some vaccines.
Scientists are also eyeing a third worrying variant that has emerged in Brazil, called P.1. Research at P.1 had been slower since its discovery in late December, leaving scientists unsure how much to worry about.
“I’m holding my breath,” said Bronwyn MacInnis, an epidemiologist at the Broad Institute.
Now, three studies offer a worrying story of the meteoric rise of P.1 in the Amazon city of Manaus. It probably surfaced there in November and then fueled a record spike in coronavirus cases. He came to dominate the city in part due to increased contagion, the survey concluded. But it also gained the ability to infect some people who had immunity from previous Covid-19 attacks. And laboratory experiments suggest that P.1 may weaken the protective effect of a Chinese vaccine now in use in Brazil.
The new studies have not yet been published in scientific journals. Its authors warn that discoveries in cells in laboratories do not always translate into the real world, and they have only just begun to understand the behavior of P.1.
“The findings apply to Manaus, but I don’t know if they apply to other places,” said Nuno Faria, a virologist at Imperial College London who helped conduct much of the new research.
But even with the mysteries that remain around P.1, experts say it is a variant to be taken seriously. “It’s okay to be concerned about P.1, and these data give us the reason,” said William Hanage, an epidemiologist at the Harvard TH Chan School of Public Health.
P.1 is now spreading to the rest of Brazil and has been found in 24 other countries. In the United States, the Centers for Disease Control and Prevention recorded six cases in five states: Alaska, Florida, Maryland, Minnesota and Oklahoma.
To reduce the risk of P.1 outbreaks and reinfections, Dr. Faria said it was important to double all the measures we have to slow the spread of the coronavirus. Masks and social distance may work against P.1. And vaccination can help to reduce its transmission and protect those who are infected from serious illnesses.
“The final message is that you need to step up all your vaccination efforts as soon as possible,” he said. “You need to be one step ahead of the virus.”
Dr. Faria and his colleagues started tracking the coronavirus when it exploded in Brazil last spring. Manaus, a city of 2 million inhabitants in the Brazilian Amazon, was hit particularly hard. At the height of spring, the cemeteries of Manaus were flooded with corpses.
But after a peak in late April, Manaus appeared to have overcome the worst of the pandemic. Some scientists thought that the fall meant that Manaus had gained herd immunity.
Dr. Faria and his colleagues looked for antibodies against the coronavirus in samples from a blood bank in Manaus in June and October. They determined that about three quarters of Manaus residents had been infected.
But towards the end of 2020, new cases began to emerge again. “In fact, there were many more cases than at the previous peak of cases, which occurred in late April,” said Faria. “And that was very intriguing for us.”
To look for variants, Dr. Faria and his colleagues launched a new genome sequencing effort in the city. Although 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 share a set of 21 mutations not seen in other viruses that circulate in Brazil. Dr. Faria sent a text message to a colleague: “I think I am seeing something very strange and I am very concerned 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 may make the variants more capable of infecting cells. Other mutations allow them to avoid antibodies from previous infections or produced by vaccines.
While Dr. Faria and his colleagues analyzed their results, researchers in Japan were making a similar discovery. Four tourists returning home from a trip to the Amazon on January 4 tested positive for the coronavirus. Genome sequencing revealed the same set of mutations that Faria and his colleagues were observing in Brazil.
Dr. Faria and his colleagues posted a description of P.1 on an online virology forum on January 12. They then investigated why P.1 was so common. His mutations may have made him more contagious, or he may have been lucky. By chance, the variant may have appeared in Manaus at a time when the city was becoming more relaxed in relation to public health measures.
It was also possible that P.1 became common because it could reinfect people. Typically, coronavirus reinfections are rare, because the antibodies produced by the body after infection are potent for months. But it was possible that P.1 carried mutations that made it more difficult for these antibodies to cling to it, allowing it to infiltrate cells and cause new infections.
The researchers tested these possibilities by tracking P.1 of their first samples in December. In early January, it represented 87% of the samples. In February, it had taken complete control.
Combining data from genomes, antibodies and medical records from Manaus, the researchers concluded that P.1 conquered the city not thanks to luck, but to biology: its mutations helped to spread. Like B.1.1.7, it can infect more people, on average, than other variants. They estimate it to be somewhere between 1.4 and 2.2 times more transmissible than other strains of coronavirus.
But it also has an advantage with mutations that allow it to escape antibodies from other coronaviruses. They estimate that out of 100 people infected in Manaus last year, somewhere between 25 and 61 of them may have been reinfected 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 dropped six times against P.1 compared to other coronaviruses. This drop could mean that at least some people would be vulnerable to new P.1 infections.
“There seems to be a growing body of evidence that suggests that most cases associated with the second wave are in fact a kind of reinfection,” said Dr. Faria.
Dr. Faria and other researchers are now looking around Brazil to observe the spread of P.1. Dr. Ester Sabino, a specialist in infectious diseases at the Faculty of Medicine of the University of São Paulo, said that one of the new outbreaks emerged in Araraquara, a Brazilian city of 223,000 inhabitants that did not have high rates in Covid-19 before the arrival of P .1 .
If people in Araraquara did not have high levels of antibodies before the arrival of P.1, she said, this suggests that the variant may be able to spread in 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 hoped it would become more common in the United States, although it had to compete with B.1.1.7, which could soon become the dominant variant in much of the country.
“At the very least, it will be one of the contestants,” said Worobey.
In their experiments, Dr. Faria and his colleagues also tested antibodies from eight people who received CoronaVac, a vaccine made in China that has been used in Brazil. They found that antibodies generated by the vaccine were less effective in stopping the P.1 variant than other types.
Dr. Faria warned that these results, derived from cells in test tubes, do not necessarily mean that vaccines will be less effective in protecting real people from P.1. Vaccines may well provide strong protection against P.1, even though the antibodies they generate are not as potent. And even if the variant does manage to infect vaccinated people, they are likely to remain protected from a severe Covid-19 attack.
For Dr. Sabino, the final importance of P.1 is the threat that variants pose when they can arise anywhere in the world.
“It’s just a matter of time and chance,” she said.