LONDON – The SARS-CoV-2 variant of concern that caused a wave of infection in Manaus, Brazil, in December and January has been found to be both more transmissible and to evade immunity conferred by prior natural infection with the virus.
A combined Brazil/U.K. genome sequencing and epidemiological study found the variant, called P.1., is between 1.4 and 2.2 times more transmissible than earlier lineages, and can evade 25% to 61% of the protective immunity elicited by previous infection.
It is not clear as yet if there is any impact on COVID-19 vaccines, with the researchers concluding, “Studies to evaluate real world vaccine efficacy in response to P.1. are urgently needed.”
Attention was drawn to P.1. after a huge jump in cases at the turn of the year in Manaus, the largest city in the Amazon region of Brazil. That was despite the fact that data from a survey in October indicated there was a seroprevalence of SARS-CoV-2 antibodies in the local population of 76%, following the first wave of infection that started in March 2020.
The question was, “Why are you seeing resurgence, despite high seroprevalence?” said Nuno Faria, reader in viral evolution at the U.K. Medical Research Center for global infectious diseases analysis at Imperial College London, who also is affiliated with the Institute of Tropical Medicine at the University of São Paulo, Brazil. “We set up genomic surveillance in Manaus and identified P.1.,” he said.
The research, published as a preprint on Biorxiv, provides clear evidence that P.1. has “altered epidemiological characteristics,” Faria told attendees of a press briefing. But he added, “Our findings from Manaus should not be generalized to other epidemiological contexts and/or other variants of concern.”
In total, P.1. has 17 mutations, of which 10 are in the spike protein by which the virus enters human cells, and which is the target of approved COVID-19 vaccines.
The key mutations in P.1. also occur in other variants of concern that have emerged independently elsewhere in the world. Faria pointed to N501Y, a mutation which occurs in both B.1.1.7, first identified in the U.K., and B1.351, first sequenced in South Africa. This mutation in the spike protein is thought to increase viral binding to the ACE2 receptor in the human host.
Another mutation common to P.1. and B1.351 is E484K, also thought to be important in viral binding to ACE2, and which has been shown to significantly reduce the neutralizing power of convalescent serum. In addition, P.1. and B1.351 also share the K417T/N mutation.
While there is “a similar constellation of mutations” in the variants, Faria said it is difficult to compare the relative risk each variant poses, because they are circulating in different backgrounds. However, it could be significant that P.1. in Manaus and the B1.351 variant in South Africa both emerged in settings where there was a high community level of seroprevalence of antibodies from the first wave of COVID-19 infections.
If the October seroprevalence study had not been done, it is likely no attention would have been paid to the resurgence in Manaus, said Ester Sabino, associate professor in the department for infectious diseases at the University of São Paulo. “We would have just said, it’s a second wave,” she noted.
In addition to immune evasion and increased transmissibility, there is some indication of an increased risk of death from P.1. infection. However, the researchers noted that was seen in the context of an overburdened health care system in Manaus, with a shortage of oxygen, for example.
The Brazil/U.K. research collaboration originally was set up in 2016 to track Zika virus. The team turned their attention to SARS-CoV-2 when the epidemic took off last year, and latterly to Manaus when it was so badly hit for a second time in December and January.
Role of genomic surveillance
The genome sequences indicate P.1. emerged around Nov. 6, 2020, and then spread rapidly, to account for 87% of cases in Manaus within seven weeks. It then spread to multiple other states in Brazil and has now been reported in 25 other countries.
The research points to the importance of genomic surveillance in controlling the COVID-19 epidemic, said Sharon Peacock, director of the U.K. program that to date has sequenced 315,000 viral samples.
Manufacturers looking to adapt vaccines in case of viral escape need that information, Peacock said. “This study shows sequencing is so important and we need to get it rolled out across the world,” she said. “It’s a global disease, and we need a global view. The key is to get as much sequence data as we can, so we understand how to modify vaccines.”
There also is some way to go in understanding how variants of concern square up against each other, and if they occur in same community, which outcompetes which. “We need to do surveillance; we will learn about the relative fitness of lineages over time,” said Peacock.
At the same time, there is now a collection of mutations that all appear to do the same things in terms of viral fitness, possibly indicating convergent evolution. “There may be a point where the virus is optimized in immune evasion and transmissibility, but we don’t know what will happen after that.” Peacock said. “We need to keep sequencing and keep an eye on it.”
On a positive note, convergent evolution means variants of concern now have similar or shared mutations, meaning vaccines manufacturers may be able to address more than one variant with a single vaccine modification, Peacock noted.