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More than 20 days after the Japan National Institute of Infectious Diseases announced the detection of a new SARS-CoV-2 variant – isolated from samples from four travelers from Amazonas, Brazil – variant P.1 has been detected in several countries other than Brazil and Japan, from the United States to Germany to the Faroe Islands, according to a World Health Organization (WHO) report.

“Now we can say that P.1 isn’t just in Manaus,” Felipe Naveca, PhD, deputy director of research at Fiocruz Amazônia, said. Medscape Medical News.

“We sorted about 100 samples in 13 cities in the state of Amazonas and in 11 of them we found P.1 circulating,” he said. He added that in December, the prevalence was 51%, and as of January 13, it has increased to 91%.

“We will increase the number of municipalities even more and sort the samples from Rondônia,” added Naveca.

The first case of infection by P.1 has occurred documented in the United States – among Minnesota residents with a history of travel to Brazil – and three cases in São Paulo were announced on January 26 by the São Paulo State Department of Health.

“As expected,” said Naveca. “When detected, the virus has been circulating for some time.”

The emergence of P.1 probably occurred between November and December 2020, and the spread of new strains appears to be fast. There’s still no data yet, but the Fiocruz Network is studying random samples from different times across the country.

Additionally, the researchers monitored the appearance of a second variant, called P.2, identified in Rio de Janeiro.

In the case of Manaus, researchers led by Naveca confirmed a trend recently announced by the Brazilian-British Center for Discovery, Diagnosis, Genomics and Epidemiology (CADDE), which includes researchers from the University of São Paulo.

Ester Sabino, MD, PhD, and her team released Preliminary results of a sample analysis of 48 tests in Manaus between 1 and 9 January. Of the 48 samples, most (85.4%) were variant P.1. The authors highlight that, despite the preliminaries, this figure is already significantly higher than the 52% of samples with variant P.1 (of 67 patients in Manaus) detected in the last 2 weeks of 2020.

Viruses like SARS-CoV-2 are changing. Of the hundreds of variants that have been detected in the first year of the pandemic, what worries scientists the most – the so-called variant of concern (VOC) – are the variants that originated in Britain, South Africa and P.1 in Brazil. .

Small differences in the viral genetic material can offer advantages, such as more infectiousness or avoidance of antibodies (either produced by previous infection or stimulated by vaccinations). In the case of the Amazonian P.1 variant, the molecular structure of the microorganism shows that it has both these advantages. Was P.1 then the cause of the chaos in the northern part of the country in Manaus?

“We don’t know whether the complicated epidemiological situation in Manaus is the cause of the P.1 line, or if the P.1 line is causing this health disorder. But if it starts to be found elsewhere and has the same effect that was observed in Manaus, overlapping with other strains, it is already a strong indicator that it is more transmissible, “Tiago Gräf, PhD, said Medscape Medical News. Gräf is a biomedical researcher at the Instituto Gonçalo Moniz, from Fiocruz, who focuses on the evolution and molecular epidemiology of viruses.

Gräf gave an example, the number of COVID-19 cases has also increased in Rio de Janeiro where, until now, the P.1 line has not been detected.

“It could be an increase in cases due to year-end parties, beaches, holidays, crowds, fatigue, euphoria with vaccines, which makes bloodlines more frequent,” he said. “We need to monitor.”

“We are trying to figure out the path the virus is taking in the state of Amazonas, but it is not yet possible,” said Naveca. He added that the pace of work of scientists in recent days has been a frenzy: “The results of the tests conducted on Sunday (January 24), we analyzed everything between [the days right after], I share with colleagues who help me with phylogenetic analysis. We’ll try to understand it better, but we still don’t have that answer. “

Focus on mutations

Presence N501Y it is this mutation that triggers fears of greater transmissibility. There is no shortcut to ascertaining whether or not a mutated strain can be transmitted. This is based on indirect evidence obtained through genomic surveillance, which identifies whether new strains are replacing old ones over time – which seems to be the case. The researchers also tried to interpret the effects of mutations cataloged by surveillance of the viral genome using computer modeling to assess whether the mutations increased the virus’ ability to interact with cells. But that wasn’t enough either.

“Soon, animal studies will begin to emerge,” explains Gräf. “After infecting mice, it needs to be seen if they produce more virus in the airways or if there are more infections in the lungs.”

P.1 is also of concern because it carries other mutations, in particular E484K, associated with reduced effects of neutralizing antibodies – which in turn can result in re-infection and a low immune response to the vaccine.

“We’ve confirmed [a P.1 reinfection]. In fact, it is one of the first samples we sequenced, “says Naveca.

In vitro studies of whether a strain can evade the immune system are relatively simple. The strains are cultured using serum from patients who have been infected with SARS-CoV-2 and, therefore, have antibodies to fight the virus. Researchers measured how many cells the new strain could infect. If it can’t infect anything, it means the patient’s antibodies are working to neutralize it. However, there are other questions that have not been answered.

Scientists still don’t know the severity of the disease caused by variant P.1, says Naveca. They also don’t know which age group is most affected. She says Medscape Medical News that he spoke with many medical colleagues, and “some report that they see younger people, others think there is no big difference between age groups. We need to increase the number of analyzes to apply statistical tests, because we have conflicting opinions, and we must be sure. “

There is also no certainty about whether this new strain will change the effectiveness of the vaccine. The WHO results on January 12 suggested the vaccine protects against the British and South African variants, but P.1 has not been studied. Samples of the new strains have been sent to Fiocruz in Rio de Janeiro to carry out a study on neutralization. According to Naveca, teams there are working in real-time in partnership with vaccine manufacturers to get results as quickly as possible.

Moderna and Pfizer have presented results showing that their vaccine protects against the British and South African variants. However, in vitro tests to measure antibody response are inconclusive.

“This in vitro testing work should be done by everyone, manufacturers and researchers,” said Sabino Medscape Medical News. “Science needs a lot of groups working to answer this question.”

“But it is logical that in vitro studies do not answer all of them. In practice, it is necessary to carry out clinical trials, following vaccinated patients, to verify that P.1 rates and transmission are the same in those who have not been vaccinated. , and monitor what happens in that region, “he said.” You may need to run tests with different vaccines to see which one responds best to this variant. “

Pharmaceutical companies are already considering possible booster doses or making adaptations to formulations. Even with the prospect of reinfection and vaccines that may not protect against some strains, there is still light at the end of the tunnel.

“Infection or a second infection in the vaccinated person is not expected to develop into severe COVID-19,” said Gräf. “Antibody immunity, even if reduced, and cellular immunity can still help, perhaps not preventing the person from becoming infected, but by reducing symptoms and the amount of virus in circulation, preventing the person from developing serious illness.”

P.2 and Other Variants

That E484K the mutation is also present in another variant from Brazil that has appeared in several states. This variant, informally called the “Rio de Janeiro” line, also has a new name: P.2.

The P.2 variant was announced in December, after being identified in Rio de Janeiro, Cabo Frio, Niterói, and Duque de Caxias, in Baixada Fluminense. It has also been identified in various states in the northern part of the country and more recently in Rio Grande do Sul. At Amazonas, the P.1 variant still dominates P.2.

“From November until now only one sample has P.2, compared to 60 from P.1,” said Naveca. However, P.2 is still a concern because of its wide geographic distribution and because it carries E484K mutations, which raise concerns about reinfection and, possibly, reducing the vaccine’s efficacy.

“P.2 has mutations that decrease the response to neutralizing antibodies, but the number of mutations is smaller and doesn’t appear to be taking the evolutionary leap that P.1 did,” Sabino said. “P.2 is not yet on the VOC list, but it turns out to have different characteristics from the others, maybe it will be on the list.”

“For now, it is still considered a strain that needs to be studied better,” he added.

That same week, two new strains of SARS-CoV-2 in southern Brazil emerged described and disclosed in two separate preprints. The new variant is not classified as a VOC, “but we need to understand it better because new variants will appear all the time,” said Naveca.

Restriction Measures

The VOC has revived the debate at the start of the pandemic about closing borders – at the national, state or city level. France is moving toward imposing restrictions, Britain is considering mandatory quarantines, Germany is studying flight cancellations, and Australia has even suspended air bubbles it has with New Zealand. Since January 26, the United States has restricted entry of non-US nationals from Brazil.

Experts still debate strategy. Some see closure as necessary. Others believe it is more important to have a good virus sequencing program to detect agile variants, as well as a strong screening program.

“I am concerned about discussing the control measures in Manaus with the situation we are in. There are patients who, if not transferred, could die. The only chance for some people is to be transferred to another location, and there is also a risk with an asymptomatic person,” he said. Naveca.

“It is best to improve genomic surveillance and tracing, limit unnecessary visits and trips, and unnecessary in person encounters,” added Gräf. “The government has to guide this.”

This article was translated and adapted from Medscape Portuguese edition.

Sabino, Naveca and Gräf have reported no relevant financial relationships.

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