Published by an Anglo-Brazilian epidemiological research center, the study revealed that in only seven weeks SARS-CoV-2 lineage P.1 became the most prevalent strain of the virus in Manaus. Analysis of more than 900 samples from patients diagnosed in the period pointed to a higher viral load (patient being transported to another state as hospitals are overwhelmed in Amazonas; photo: André L. P. de Souza/Wikimedia Commons)

Published on 03/15/2021

By Karina Toledo  |  Agência FAPESP – The Brazilian variant of the novel coronavirus, known as P.1, probably emerged in Manaus, the capital of Amazonas State, in mid-November 2020, about a month before a sharp rise was reported in the number of hospitalizations for treatment of severe acute respiratory syndrome in the city. In only seven weeks, P.1 became the most prevalent SARS-CoV-2 lineage in the region, according to researchers affiliated with the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) in an article published by CADDE on its website on February 27, 2021.

The findings of the group coordinated by Ester Sabino, a professor at the University of São Paulo (USP) in Brazil, and Nuno Faria, a professor at Oxford University in the United Kingdom, were based on genomic analysis of 184 nasopharyngeal swabs from patients diagnosed with COVID-19 by Manaus laboratories between November 2020 and January 2021.

Mathematical modeling and cross-tabulation of genomic and mortality data led the CADDE researchers to conclude that P.1 may be 1.4-2.2 times more transmissible than previous lineages. They also estimated that P. 1 may be able to circumvent the immune system and cause another infection in a significant proportion of individuals already infected by SARS-CoV-2 (between 25% and 61%). 

“These numbers are an approximation based on modeling. In any event, the message from the data is that even people who have had COVID-19 should continue taking precautions,” Sabino, told Agência FAPESP. “The new strain is more transmissible and can infect individuals with antibodies against the virus. That’s what happened in Manaus, where most of the population were immune and even so there was a fresh outbreak of major proportions.”

The modeling part of the research was conducted in collaboration with Imperial College London (ICL). The study was supported by FAPESP and is currently being peer-reviewed.

The group’s analysis of over 900 samples supplied by the Manaus laboratories, including the 184 swabs they sequenced, showed that viral load increased as P.1 became more prevalent. According to Sabino, viral load is typically very high at the start of an epidemic and declines over time. The researchers are not sure whether the increase observed in the samples is due to an epidemiological factor or evidence that P.1 replicates more in the human organism than other strains. “The latter explanation seems highly probable and would tell us why transmission of the variant is faster,” Sabino said.

Another study shows that viral load in individuals infected by P.1 can be up to ten times higher. This study was conducted by researchers at FIOCRUZ Amazonia, the main unit of federal research institution Fundação Oswaldo Cruz in Brazil’s North region. It too was published on February 27.

According to the CADDE article, by February 24 P.1 had been detected in six Brazilian states, which received 92,000 passengers on flights from Manaus in November 2020. Most (about 30,000) disembarked in São Paulo, followed by other cities in Amazonas and destinations in Pará, Rondônia, Ceará and Roraima. The data, therefore, suggests multiple introductions of the variant from Amazonas to other states, the authors conclude.

Key mutations

Viral genomes in the 184 samples were sequenced using a technology called MinION, which is portable and inexpensive, facilitating analysis on a large enough scale to understand how the virus is evolving.

Based on the molecular clock, a genomic technique that measures the amount of time since species or lineages diverged, the researchers found that P.1 is a descendant of B.1.128, the lineage first detected in Manaus in March 2020. Compared with this parent strain, P.1 has 17 mutations, ten of which are in the spike protein used by the virus to bind to the ACE-2 receptor on the surface of human cells and infect its host.

The authors consider three mutations – N501Y, K417T, and E484K – most important as they are located in the spike’s docking tip, known as the receptor-binding domain (RBD). According to Sabino, these three key mutations are identical to those found in B.1.351, the more transmissible variant first detected in South Africa, while B.1.1.7, the variant of concern first detected in the UK, has only the mutation E484K in its RBD. For the authors, the data points to a process of convergent evolution in which certain mutations that gave the virus a competitive advantage emerged at the same time in different parts of the world. Natural selection enabled these lineages or variants to survive in greater quantities than their predecessors in the same regions.

The authors say they do not yet know why P.1 evolved so fast. “Various mutations that facilitate transmission of the virus appeared suddenly. That doesn’t happen very often. For example, there is only one such mutation in P.2, which is also a descendant of B.1.128,” Sabino noted. One of the possible explanations, she said, is that the virus gained time to evolve by infecting patients with compromised immune systems. 

“Until equitable allocation and access to effective vaccines are available for everyone, non-pharmacological interventions [social distancing, mask-wearing and hand hygiene] should continue to play an important role in reducing the emergence of novel variants,” the authors conclude.

 

Source: https://agencia.fapesp.br/35414