THE Brazilian variant of the new coronavirus – known as P.1. or variant of Manaus – it probably emerged in the Amazon capital in mid-November 2020, about a month before the number of hospitalizations for severe acute respiratory syndrome in the city made a leap. In just seven weeks, P.1. became the most prevalent strain of SARS-CoV-2 in the region, report researchers from the Brazil-UK Center for Discovery, Diagnosis, Genomics and Epidemiology of Arbovirus ( CADDE ) in an article published on its website on Friday, the 27th of February.
The conclusions of the group coordinated by Ester Sabino , from USP, and Nuno Faria, from Oxford University (United Kingdom), are based on the genomic analysis of 184 samples of nasopharyngeal secretion from patients diagnosed with covid-19, in a laboratory in Manaus, between November 2020 and January 2021.
Through mathematical modeling, crossing genomic and mortality data, the CADDE team calculates that P.1. between 1.4 and 2.2 times more transmissible than the strains that preceded it. Scientists further estimate that in part of individuals already infected with SARS-CoV-2 – somewhere between 25% and 61% – the new variant is able to circumvent the immune system and cause a new infection. The modeling work was done in collaboration with researchers at Imperial College London (United Kingdom).
“These numbers are an approximation, as it is a model. Anyway, the message that the data sends is: even those who already had COVID-19 need to continue to be cautious. The new variant is more transmissible and can infect even those who already have antibodies against the new coronavirus. This is what happened in Manaus. Most of the population already had immunity and even then there was a major epidemic ”, says Sabino to the São Paulo State Foundation for Research Support (Fapesp)
The research was supported by Fapesp and is in the process of peer review.
Analyzes made by the group on more than 900 samples collected in the same laboratory in Manaus, including 184 that were sequenced, indicate that the viral load present in the patients’ secretion increased with the P.1 variant. became more prevalent.
According to Sabino, it is common at the beginning of an epidemic that the viral load of those infected is higher and decreases over time. For this reason, the researchers are not sure if the increase observed in the analyzed samples can be explained by a merely epidemiological factor or if, in fact, it indicates that P.1. it can replicate more in the human organism than the previous lineage. “This second option seems very likely and would explain why the transmission of the new variant is faster”, comments the researcher.
Another study also released on Friday (27) by researchers from the Oswaldo Cruz Foundation (Fiocruz) Amazônia indicates that in individuals infected with P.1. the viral load in the body can be up to ten times higher.
In the CADDE article, the researchers report that, until February 24, 2021, variant P.1. it had already been detected in six Brazilian states, which, in all, received 92 thousand air passengers from Manaus in November 2020. Of these, the majority had São Paulo as their destination (just over 30 thousand). Then came other cities in Amazonas, Pará, Rondônia, Ceará and Roraima. According to the authors, therefore, it is likely that there have been multiple introductions of the new variant in these states.
The sequencing of the viral genome of the 184 samples was done with a technology known as MinION, which, because it is portable and inexpensive, makes it possible to carry out studies that help to understand the process of evolution of the virus.
By a genomic technique called the molecular clock, the researchers concluded that P.1. descends from variant B.1.128, which was first identified in Manaus in March 2020. When compared to the parent strain, variant P.1. it has 17 mutations, ten in the Spike protein – used by the virus to connect with the ACE-2 protein on the surface of human cells to make infection possible.
Three mutations are considered most important – the N501Y, the K417T and the E484K – as they are located at the tip of the Spike protein, in a region known as RBD (acronym in English for Receptor Binding Domain). It is there that the connection between the virus and the human cell occurs.
According to Sabino, these three key mutations are identical to those found in the most transmissible variant reported in South Africa (B.1.351). The variant of concern discovered in the United Kingdom (B.1.1.7.) Shows only the E484K mutation in the RBD region. For the authors, the data indicate that there was a process of convergent evolution, that is, certain mutations that confer an advantage to the virus appeared in parallel in strains from different geographic regions. By natural selection, these variants have been standing out from the strains previously prevalent in these locations.
In the case of P.1., The authors report, there was a period of rapid molecular evolution and it is not yet known why. “Suddenly, several mutations appeared that facilitate the transmission of the virus, something unusual. To give you an idea, the variant P.2., Which also descends from B.1.128, presents only one mutation of this type ”, says Sabino.
One of the possible explanations for the phenomenon, according to the researcher, is that the virus had more time to evolve when infecting a patient with a compromised immune system.
“Until effective vaccines are available to all, non – pharmacological interventions [social distancing, mask use and hand hygiene] continue to be necessary and important to reduce the emergence of new variants,” note the researchers of CADDE .