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Brazilian variant likely more transmissible and able to evade immunity — Manaus study

Even though more and more vaccines against the coronavirus are being administered all over the world, many countries are still battling with outbreaks and face difficulties providing help to those in need. One of those countries is Brazil. Here, they are facing a massive second wave outbreak, many daily deaths and instances of the health care systems collapsing. In the city of Manaus things have looked exceptionally bleak from December and through to the early spring.

The city was hit so hard by the first wave in 2020 that it was actually thought to be one of the few places in the world to have reached herd immunity. An estimated 75% of the population in the city had been infected. But then the second wave hit in November and December.

Now, a study published with collaborators from Brazil, the UK and University of Copenhagen has shed a light on why Manaus is facing these difficulties again.

"Our main explanation is that there is an aggressive variant of the coronavirus called P.1 which seems be the cause of their problems. Our epidemiological model indicates that P.1 is likely to be more transmissible than previous strains of coronavirus and likely to be able to evade immunity gained from infection with other strains," says corresponding author to the new study, Samir Bhatt, a researcher at the department of public health at University of Copenhagen.

The researchers used many forms of data from Manaus to characterise P.1 and its properties including 184 samples of genetic sequencing data. They find that genetically speaking P.1 is different from the previous strains of coronavirus. It has acquired 17 mutations including an important trio of mutations in the spike protein (K417T, E484K and N501Y).

"Our analysis shows that P.1 emerged in Manaus around November 2020. It went from not being detectable in our genetic samples to accounting for 87% of the positive samples in just seven weeks. It has since spread to several other states in Brazil as well as many other countries around the world," says Samir Bhatt.

The researchers then used an epidemiological model to estimate how transmissible P.1 seemed to be. As well as estimating signs of P.1 evading immunity gained from previous infection.

"Roughly speaking, our model incorporates many data sources such as mortality counts and genetic sequences and compares two different virus strains to see which one best explains the scenario that unfolded in Manaus. One was the 'normal coronavirus' and the other was dynamically adjusted using machine learning to best fit the actual events in Brazil," says Bhatt.

This modelling allowed the researchers to conclude that P.1 is likely to be between 1.7 and 2.4 times more transmissible than non-P1-lineages of the coronavirus.
They also conclude that P.1 is likely to be able to evade between 10% and 46% of the immunity gained from infection with non-P.1 coronavirus.

"As researchers, we have to caution extrapolating these results to be applicable anywhere else in the world. However, our results do underline the fact that more surveillance of the infections and of the different strains of the virus is needed in many countries in order to get the pandemic fully under control," ends Bhatt.

 

Study details
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Nuno R Faria, Thomas A Mellan, Charles Whittaker, Ingra M Claro, Darlan da S Candido, Swapnil Mishra, Myuki AE Crispim, Flavia CS Sales, Iwona Hawryluk, John T McCrone, Ruben JG Hulswit, Lucas AM Franco, Mariana S Ramundo, Jaqueline G de Jesus, Pamela S Andrade, Thais M Coletti, Giulia M Ferreira, Camila AM Silva, Erika R Manuli, Rafael HM Pereira, Pedro S Peixoto, Moritz UG Kraemer, Nelson Gaburo, Cecilia da C Camilo, Henrique Hoeltgebaum, William M Souza, Esmenia C Rocha, Leandro M de Souza, Mariana C de Pinho, Leonardo JT Araujo, Frederico SV Malta, Aline B de Lima, Joice do P Silva, Danielle AG Zauli, Alessandro C de S Ferreira, Ricardo P Schnekenberg, Daniel J Laydon, Patrick GT Walker, Hannah M Schlüter, Ana LP dos Santos, Maria S Vidal, Valentina S Del Caro, Rosinaldo MF Filho, Helem M dos Santos, Renato S Aguiar, José L Proença-Modena, Bruce Nelson, James A Hay, Mélodie Monod, Xenia Miscouridou, Helen Coupland, Raphael Sonabend, Michaela Vollmer, Axel Gandy, Carlos A Prete, Vitor H Nascimento, Marc A Suchard, Thomas A Bowden, Sergei L K Pond, Chieh-Hsi Wu, Oliver Ratmann, Neil M Ferguson, Christopher Dye, Nick J Loman, Philippe Lemey, Andrew Rambaut, Nelson A Fraiji, Maria do PSS Carvalho, Oliver G Pybus, Seth Flaxman, Samir Bhatt, Ester C Sabino

Published in Science on 14 April 2021

 

Abstract
Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1, 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 mid-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 1.7–2.4-fold more transmissible, and that previous (non-P.1) infection provides 54–79% of the protection against infection with P.1 that it provides against 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.

 

University of Copenhagen material

Science study (Open access)

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