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Genomic, Epidemiological Analysis Traces SARS-CoV-2 P.1 Lineage Emergence in Brazil

NEW YORK — The P.1 lineage of SARS-CoV-2 likely arose in Manaus, Brazil, in mid-November 2020, according to a new genomic and epidemiological study. It further found that the viral variant may be more transmissible and previous SARS-CoV-2 infection may provide reduced protection against it.

Brazil has been particularly hard hit by the COVID-19 pandemic with 13.6 million reported cases and nearly 360,000 deaths, according to the Johns Hopkins Coronavirus Resource Center. One study suggested that more than 70 percent of the Manaus population was infected with SARS-CoV-2 within seven months of the virus's arrival there.

Despite that high level of infection, the city experienced another wave of SARS-CoV-2 infections in late 2020 and early 2021. As they reported in Science on Wednesday, researchers led by the University of São Paulo's Ester Sabino sequenced and analyzed samples from this resurgence in Manaus to trace it back to the emergence of a novel variant of concern, dubbed P.1.

"Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness," the researchers wrote in their paper.

Sabino and her colleagues sequenced SARS-CoV-2 isolates from 184 samples from people seeking COVID-19 testing in Manaus between November and December 2020.

Through this they uncovered the novel SARS-CoV-2 viral lineage P.1, which harbors 17 amino acid changes, including 10 affecting the spike protein. Eight of those lineage-defining changes are under diversifying positive selection and three — N501Y, K417T, and E484K — are in the spike protein receptor binding domain. The same three residues are altered in the B.1.351 variant of concern and the N501Y change is present in the B.1.1.7 variant, pointing to possible convergent molecular adaptation, they noted.

A phylogenetic analysis found that P.1 and another lineage named P.2 descended from the B.1.1.28 lineage that was first uncovered in Brazil in March 2020. Further molecular clock analysis traced the emergence of P.1 to mid-November 2020. Its emergence was preceded by a period of faster molecular evolution, which the researchers pointed out was also observed in the emergence of the B.1.1.7 lineage and hypothesized to have occurred in a patient who was immunocompromised or chronically infected.

In addition, this timeframe of when they estimated P.1 to have emerged is about three to four weeks before Manaus experienced a confirmed rise in COVID-19 cases.

Using modeling, the researchers further explored whether the new wave of infections was due to increased severity or transmissibility of P.1 or to declining prior immunity among patients. Their analysis pointed to differences between the epidemiological characteristics of P.1 and other SARS-CoV-2 lineages, suggesting the viral resurgence in Manaus is not solely due to waning immunity.

In particular, they estimated that P.1 is between 1.7 times and 2.4 times more transmissible than non-P.1 strains and can evade between 21 percent to 46 percent of immunity elicited by infections with non-P.1 strains.

The researchers also uncovered an increase in mortality following the emergence of the P.1 variant, but said that they could not disentangle whether P.1 is more deadly or if the effect was due to stress on the healthcare system in Manaus, or both.

Sabino and her colleagues noted in their paper that the P.1 lineage is spreading quickly across Brazil and has been found in three dozen other countries. They added that viral genomic surveillance strategies are often inadequate and that more data is needed to study their effect.

"Sustainable genomic surveillance efforts to track variant frequency coupled with analytical tools to quantify lineage dynamics and anonymized epidemiological surveillance data could enable enhanced real-time surveillance of variants of concern worldwide," they wrote, adding that studies examining "real-world vaccine efficacy in response to P.1 are urgently needed."