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

  1. Nuno R. Faria
  2. Thomas A. Mellan
  3. Charles Whittaker
  4. Ingra M. Claro
  5. Darlan da S. Candido
  6. Swapnil Mishra
  7. Myuki A. E. Crispim
  8. Flavia C. S. Sales
  9. Iwona Hawryluk
  10. John T. McCrone
  11. Ruben J. G. Hulswit
  12. Lucas A. M. Franco
  13. Mariana S. Ramundo
  14. Jaqueline G. de Jesus
  15. Pamela S. Andrade
  16. Thais M. Coletti
  17. Giulia M. Ferreira
  18. Camila A. M. Silva
  19. Erika R. Manuli
  20. Rafael H. M. Pereira
  21. Pedro S. Peixoto
  22. Moritz U. G. Kraemer
  23. Nelson Gaburo
  24. Cecilia da C. Camilo
  25. Henrique Hoeltgebaum
  26. William M. Souza
  27. Esmenia C. Rocha
  28. Leandro M. de Souza
  29. Mariana C. de Pinho
  30. Leonardo J. T. Araujo
  31. Frederico S. V. Malta
  32. Aline B. de Lima
  33. Joice do P. Silva
  34. Danielle A. G. Zauli
  35. Alessandro C. de S. Ferreira
  36. Ricardo P. Schnekenberg
  37. Daniel J. Laydon
  38. Patrick G. T. Walker
  39. Hannah M. Schlüter
  40. Ana L. P. dos Santos
  41. Maria S. Vidal
  42. Valentina S. Del Caro
  43. Rosinaldo M. F. Filho
  44. Helem M. dos Santos
  45. Renato S. Aguiar
  46. José L. Proença-Modena
  47. Bruce Nelson
  48. James A. Hay
  49. Mélodie Monod
  50. Xenia Miscouridou
  51. Helen Coupland
  52. Raphael Sonabend
  53. Michaela Vollmer
  54. Axel Gandy
  55. Carlos A. Prete
  56. Vitor H. Nascimento
  57. Marc A. Suchard
  58. Thomas A. Bowden
  59. Sergei L. K. Pond
  60. Chieh-Hsi Wu
  61. Oliver Ratmann
  62. Neil M. Ferguson
  63. Christopher Dye
  64. Nick J. Loman
  65. Philippe Lemey
  66. Andrew Rambaut
  67. Nelson A. Fraiji
  68. Maria do P. S. S. Carvalho
  69. Oliver G. Pybus
  70. Seth Flaxman
  71. Samir Bhatt
  72. Ester C. Sabino

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Abstract

Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from Sã o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response.

Science , abh1558 and abh2644, this issue p. 821 and p. 815

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  1. Version published to 10.1126/science.abh2644
  2. NCRC

    Our take

    This study, available as a preprint and thus not yet peer-reviewed, documented the emergence of the P.1 variant of concern in Manaus, Brazil and the wave of COVID-19 infections associated with its spread. The authors demonstrate that this variant is likely more transmissible than other lineages circulating locally, and presented several hypotheses for why this variant may be more transmissible. The paper demonstrated that genomic surveillance is crucial to the detection of new SARS-CoV-2 variants of concern. Further studies will be needed to understand the cause of this increased transmissibility, which may be useful in curtailing the variant’s spread.

    Study design

    other

    Study population and setting

    This study analyzed SARS-CoV-2 genomes from 184 samples from patients seeking COVID-19 testing in Manaus, Brazil, with the goal of understanding the second wave of disease in the region. The 184 genomes were derived from 436 PCR-confirmed or suspected SARS-CoV-2 samples collected between November 1, 2020 and January 9, 2021, and these sequences were analyzed alongside publicly available genomes from Brazil. The authors also used a larger sample of 942 samples from Brazil for which quantitative RT-PCR data were available (cycle threshold [Ct] values) to explore potential viral load differences between sequences belonging to the P.1 lineage identified in Manaus and other virus lineages. Finally, the authors used mobility data (airline data from Brazil’s Civil Aviation Agency and cell phone data from In Loco) to explore movement of the P.1 lineage, and epidemiological data such as death records (from a hospitalization database) to model the transmission dynamics of P.1 and non-P.1 virus.

    Summary of main findings

    The authors found that the second wave of COVID-19 in Manaus, Brazil was associated with the emergence and spread of a new SARS-CoV-2 lineage of concern: P.1. This lineage contains 17 amino acid changes compared to the Wuhan-Hu-1 reference genome, including 10 mutations in the spike protein, and is a descendent of lineage B.1.1.128, which was detected in Brazil in March 2020. The data presented in this study suggest the P.1 lineage emerged approximately one month prior to the resurgence of COVID-19 in Manaus, which supports the hypothesis that the second wave of disease was associated with the new variant. They also found evidence that this variant likely emerged in Manaus, and that the variant spread from Amazonas (the state in which Manaus is located) into Brazil’s southeastern states, a finding supported by both genomic and air travel data. Mathematical modeling showed that virus belonging to the P.1 lineage is likely 1.4–2.2 times more transmissible than local non-P1 lineages, though these results are not generalizable to other settings (since the authors were only able to compare to the other lineages circulating locally). To explain variations in transmissibility, the authors investigated viral Ct values over time, and found that increased transmissibility of P.1 virus could be due to higher viral loads or longer infection, though this finding was inconclusive. The authors also hypothesized that mutations in the receptor binding domain that are present in the P.1 lineage (as well as the B.1.351 lineage of concern) could improve host cell entry, but they are not able to confirm this hypothesis.

    Study strengths

    The authors performed robust phylogenetic analyses of SARS-CoV-2 genomes from Brazil, which allowed them to estimate the date and location of emergence of theP.1 variant. The availability of epidemiological and mobility data allowed them to corroborate their findings, lending additional certainty to their conclusions.

    Limitations

    As the authors point out, their observation of increased transmission potential of the P.1 lineage is specific to the local context – without using a more global dataset, they are not able to make more general conclusions about the transmissibility of the variant. Similarly, not enough data were presented on Ct values (e.g., minimal details on where these samples were from, no lineage information available for the majority of samples, no data presented on what day of infection each sample was tested) to understand if viral loads were truly higher in virus belonging to the P.1 lineage.

    Value added

    This study documents the emergence of the P.1 variant of concern and describes a large outbreak associated with this new variant. It highlights the importance of tracking these variants and the need for further studies to characterize transmissibility of the variant compared to other circulating lineages, both in Brazil and worldwide.

  3. ScreenIT

    SciScore for 10.1101/2021.02.26.21252554: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Materials and Methods:
    Methods
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.02.26.21252554v1 on medRxiv