Wednesday, March 03, 2021

Imperial College London: Preprint - Genomics and Epidemiology of a Novel SARS-CoV-2 Lineage in Manaus, Brazil

Amazonas State, Brazil - Credit Wikip 


Brazil's northwestern Amazonas state saw some of the highest COVID attack rates on the planet last spring, and by late 2020 seroprevalence studies conducted in Manaus - the capital and largest city in Amazonas - indicated 3/4ths of the population had already been infected with the virus and were presumably immune.

While arguably not enough to convey community immunity, reports of a new and devastating outbreak in Amazonas state beginning last December (see Brazil: Amazonas Transfers 235 COVID Cases To Other States Amid Critical Oxygen Shortage) were unexpected. 

In late January, in The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence, we looked at the possible causes of this unusual wave of new infections in Amazonas. The authors stated that while it is possible that previous infection rates were overestimated, it was more likely that some combination of these other factors were at work:

A) preexisting immunity has waned over time;

B) the new P.1 variant is evades prior immunity from earlier variants (see Brazil MOH Confirms Reinfection With COVID Variant P.1 In Amazonas);

C) the new P.1 variant is vastly more transmissible than earlier variants

Also in January, we saw a technical report from FIOCRUZ (Fundação Oswaldo Cruz) that provided the latest genomic sequencing data from Amazonas state, and found that the P.1 variant has rapidly overtaken all other variants in the region, jumping from 51% of all sequenced samples in December to 91% by the first half of January.

A more robust COVID variant - particularly one capable of evading prior immunity - would be a serious setback, as it could potentially reinvigorate the pandemic, just as vaccines and acquired immunity were starting to make inroads. 

Yesterday Imperial College London, in concert with researchers at the University of São Paulo (and others), published a new report (yet to be peer-reviewed) on the genomics and epidemiology of the P.1 lineage in Manaus, Brazil. 

They found this emerging variant to be more transmissible, and quite adept at evading prior acquired immunity in a large segment of the community, both of which helped to create the massive second wave in Amazonas. 

We've excerpts from a press release by Imperial College London, and a link to the the lengthy (44-page) preprint article.  You'll want to follow the link to read the full report, including the Q&A section at the end. 

More transmissible and evasive SARS-CoV-2 variant growing rapidly in Brazil
by Andrew Scheuber, Dr Sabine L. van Elsland 02 March 2021
The P.1 lineage of the SARS-CoV-2 variant first observed in Brazil has driven a second wave of infections even in a region hit hard by the first wave.

The findings, which may point to risk of re-infection or increased transmissibility, come from researchers at the University of São Paulo in collaboration with Imperial College London and the University of Oxford.
P.1 lineage around the world

Despite very high infection rates in the Amazon region, a second wave of infection hit in Manaus, Brazil between December 2020 and January 2021. Genomic sequencing of clinical samples from Manaus found that this second wave was associated with the emergence and rapid spread of a new Variant of Concern (VOC), the P.1 lineage.

Statistical analysis of genome data suggests that the P.1 lineage has likely been circulating in Manaus since early November 2020.

This lineage has been identified in over 20 countries worldwide and continues to spread, including several recently confirmed cases in the UK. 

Global collaborative efforts on rapid virus genome sequencing are allowing us to identify SARS-CoV-2 lineages of concerns in near real-time.Prof Ester SabinoStudy author

Several genetic changes - substitutions and deletions - in this new P.1 lineage may have immunological significance. The team identified 17 mutations for this VOC, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor: a protein on the cell surface functioning as an entrance into the cell for SARS-CoV-2. Using analysis of genome sequence data, researchers were able to date back the emergence of the P.1 VOC to early November 2020.

More transmissible and evasive

The researchers found that the new P.1 lineage is growing rapidly in Brazil, is likely more transmissible than other variants, and may have the ability to evade protective immunity. The researchers estimate that the P.1 VOC is between 1.4–2.2 times more transmissible than non-VOC lineages. In addition, they estimate that the P.1 VOC evades 25-61% of protective immunity arising from infection with previously circulating variants. The exact trade-off between increased transmissibility and evading immunity is not currently known.

The full manuscript can be viewed at:

Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

Abstract: Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. 

Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4–2.2 times more transmissible and able to evade 25-61% of protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

One-Sentence Summary: We report the evolution and emergence of a SARS-CoV-2 lineage
of concern associated with rapid transmission in Manaus.

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