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Since the end of December, the number of covid-19 cases increased significantly in Manaus, Brazil. This rapid increase surprised some scientists, namely the Portuguese Nuno Faria, who had already published an article in the journal. Sciences where it was estimated that 76% of the population of Manaus had been exposed to the SARS-CoV-2 coronavirus in October. The scientist says that what is happening in this area of Brazil is “worrying” and his team puts this Wednesday in the publication The lancet various hypotheses about what may be happening in Manaus. A new variant of the virus aided by mutations known as Nelly me Erik here it can play a decisive role.
When the number of cases was increasing rapidly in Manaus, the team of Nuno Faria, a virologist at Imperial College London, detected a new variant in Manaus, P.1. The scientist tells the PUBLIC that, as of January 10 of this year, he shared the data with the World Health Organization (WHO), the Pan American Health Organization (PAHO), the Oswaldo Cruz Foundation (Fiocruz) and the Ministry of Health. Manaus Health.
Almost 40 cases associated with this variant have already been identified and more than 20 are from Manaus, according to the portal. SARS-CoV-2 lineages. Besides Brazil, at least seven other countries have reported this lineage. So far, there is no indication that it has been detected in Portugal. It is also not sure yet if it will be even more transmissible than other variants in circulation, but it is already suspected that it is.
According to data from Nuno Faria, in Manaus, for now, the frequency of the variant in December was 52.2% and in January 85.4%. Thus, in January it is already dominant: of the 48 genomes sequenced this month, 41 were from P.1; three from P.2 (another variant) and four from other variants. In total, to have these data for December and January, 142 virus samples from cases in Manaus were sequenced, 76 of which were from P.1 (December 35 and January 41). Still, between March and November 2020, it was absent in 26 genome samples collected in that area.
Escape the immune system and reinfections.
The mutations found in this variant also provide important clues. “This strain has 17 unique mutations”, emphasizes Nuno Faria. Ten of them are found in the peak protein, essential for the invasion and multiplication process of the virus in the host.
Also present in the new variants detected in South Africa and the United Kingdom, P.1 has the N501Y mutation (known as “Nelly”For some scientists), which apparently increases the strength of the connection between the spike protein and the receptor in cells, which will facilitate their entry there. Since this genetic alteration is also found in other variants that will no longer be transmissible, Kristian Andersen (from the US Scripp Research Institute) told the journal. Sciences who does not work alone: ”The Nelly you can be innocent, except maybe if you’re in bad company. “The variant found in the UK is suggested to be between 40% and 70% more transmissible. The South African variant has also been observed to be associated with a greater transmission potential.
In the P.1 spike protein, the E484K mutation (also found in the South African strain), known as Erik. Several studies suggest that this mutation is associated with an escape from the immune system, which may even facilitate reinfection.
In Brazil, at least three cases of reinfection have already been detected in which the second infection was linked to a viral variant with E484K, says Nuno Faria. “But, to know exactly the role of E484K, we would need to do longitudinal studies with genetic sequencing of both the virus that caused the first infection and the virus that caused the second infection, which is not easy in an emergency and a pandemic. context “, he explains. And can P.1 have an impact on vaccines? Nuno Faria emphasizes that, so far, it is unknown.” Several studies are being carried out in the coming weeks. I think we will soon have a more definitive answer ”.
Coronavirus SARS-CoV-2
NIAID
One of the questions on the table is whether this variant is influencing the increase in cases in the state of Amazonas, where Manaus is located. “Very possibly this new variant is strongly associated with the increase in cases in Amazonas”, considers the Portuguese researcher. As for what worries him the most, Nuno Faria says: “The context is worrying.”
In December I published a study in Sciences with the first estimates of seroprevalence in Manaus and São Paulo. “We estimate that 76% of the population of Manaus was exposed to SARS-CoV-2 until October 2020,” he summarizes. The virologist points out that, although these estimates were obtained through blood donor data, other serological studies in the Amazon region have already suggested that between 60 and 70% of the populations were infected by this coronavirus. But in late December and in recent weeks, a rapid increase in cases began to be observed in Manaus. “The number of cases was even higher than in the first wave, peaking at the end of April, and there are several reports of people becoming infected in both the first wave and this second wave,” he says.
Therefore, one of the hypotheses was that we would be facing a new lineage that would be transmitted faster or better. “When we sequenced samples from December and January, that’s exactly what we found: a new strain with a constellation of mutations previously associated with immune escape (E484K) and faster transmission (N501Y).”
The four possible explanations
In this Wednesday’s article in The lancet, it is highlighted that the estimated attack rate (or incidence) in Manaus would be above the theoretical threshold of group immunity (67%). Even so, an “abrupt increase in the number of admissions for covid-19 in hospitals in Manaus during January 2021 is unexpected and worrying,” it read. Since the April peak, covid-19 hospitalizations in Manaus remained stable and “quite low” between May and November, despite the relaxation of control measures during that period.
For this reason, along with other researchers, Nuno Faria presents four possible and “non-exclusive” explanations for the resurgence of covid-19 cases in Manaus. First, the attack rate may have been overestimated during the first wave of the pandemic, and the population may have remained below the group immunity threshold until early December. In this scenario, it is suggested that the resurgence can be explained by a “great mix between infected and susceptible individuals” during December. It is also noteworthy that even a lower limit of herd immunity could have been important in preventing a major outbreak.
In the second explanation, it is suggested that immunity against infection may have already started to decline in December due to a general decline in immune protection against SARS-CoV-2 after the first infection. But although the observed decrease in some antibodies may reflect a loss of immune protection, other factors, such as T-cell responses, are also involved in immunity.
It should be noted that a study with British health professionals has already shown that reinfection is rare up to six months after the first infection. The first infections in Manaus occurred between seven and eight months before this resurgence. “It is longer than the period covered by the UK study, but still suggests that loss of immunity alone does not fully explain the recent resurgence,” he said. It is also believed that people’s behavior does not explain the resurgence, because their mobility has declined since mid-November.
In a third point, it is indicated that SARS-CoV-2 strains can escape the immunity generated in response to previous infections. There, reference is made to the variants detected in Brazil (P.1), South Africa and the United Kingdom, which are “unusually divergent and each has a unique constellation of mutations of potential biological importance.” There is already a case of reinfection associated with P.1 in Manaus. Another new variant in Brazil, P.2, which also has the E484K mutation, has already been detected in two people reinfected in Brazil.
Nuno Faria
DR
In the fourth and final explanation, it is noted that the lines in circulation in the second wave may be inherently more transmissible than the pre-existing variants in Manaus. As the impact of P.1 on transmissibility is not yet known, it is suggested that more research is needed.
After the possible explanations, there is a warning: “The new strains of SARS-CoV-2 can cause a resurgence of cases in the places where they circulate if they have a higher transmissibility compared to pre-existing strains and if they are associated with antigens.”
Therefore, it is requested that it is necessary to rapidly investigate the characteristics of the new variants at the genetic, immunological, clinical and epidemiological levels. Genomic and serological surveillance also remains a priority, as does the determination of the efficacy of covid-19 vaccines against P.1 and other variants with the potential to escape the immune system. Genotyping viruses from vaccinated and COVID-19 patients who have not been protected by vaccination can help to understand whether there are strains more frequently associated with reinfection. Nuno Faria stresses that this “should happen at a very low rate with effective vaccines.”
Finally, it is recommended that the results of these studies be shared rapidly wherever variants emerge and spread. The team itself shares its data in site from the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology and guarantees: “We will continue to share data on genetic sequencing and results from Manaus through open access data platforms, such as GISAID and Virological”.
As for the measures to control the P.1 variant, Nuno Faria says that they should be the same as those already used to control SARS-CoV-2, such as effective masks, social distancing and hand washing. The scientist adds that these measures “will be reinforced with vaccination to immunize people at risk and, ultimately, protect entire populations.”
