1887

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages may impact COVID-19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS-CoV-2 lineages and the low number of samples sequenced from the total number of infections.

Funding
This study was supported by the:
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 313403/2018-0)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 302317/2017-1)
    • Principle Award Recipient: GonzaloBello
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 303902/2019)
    • Principle Award Recipient: GabrielLuz wallau
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 306146/2017-7)
    • Principle Award Recipient: FelipeGomes Naveca
  • Pan American Health Organization Brazil Country Office and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Award Finance Code 001)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award CNPQ BRICS STI 4 441080/2020-0)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award Covid 10 MCTI 402457/2020-0)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • INCT-FCx (Award 465259/2014-6)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • Inova Fiocruz/Fundação Oswaldo Cruz (Award VPPCB-005- FIO-20-2-87)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • Inova Fiocruz/Fundação Oswaldo Cruz (Award VPPCB-007-FIO-18-2-30)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • FAPERJ (Award E-26/210.196/2020)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • FAPERJ (Award E-203.074/2017)
    • Principle Award Recipient: MarildaMendonça Siqueira
  • FAPEAM (Award 005/2020)
    • Principle Award Recipient: FelipeGomes Naveca
  • MS/FNDCT/SCTIE/Decit (Award 403276/2020-9)
    • Principle Award Recipient: FelipeGomes Naveca
  • MS/FNDCT/SCTIE/Decit (Award 402457/2020-9)
    • Principle Award Recipient: FelipeGomes Naveca
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000751
2022-03-17
2022-05-18
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/3/mgen000751.html?itemId=/content/journal/mgen/10.1099/mgen.0.000751&mimeType=html&fmt=ahah

References

  1. Dezordi FZ, Resende PC, Naveca FG, do Nascimento VA, de Souza VC et al. Unusual SARS-CoV-2 intrahost diversity reveals lineage superinfection. Figshare 2022. 10.6084/m9.figshare.19361270.v1
    [Google Scholar]
  2. Jaroszewski L, Iyer M, Alisoltani A, Sedova M, Godzik A. The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins. PLoS Comput Biol 2021; 17:e1009147 [View Article] [PubMed]
    [Google Scholar]
  3. Mullen JL, Tsueng G, Abdel Latif A, Alkuzweny M, Cano M et al. outbreak.info; 2021 https://outbreak.info/
  4. Faria NR, Mellan TA, Whittaker C, Claro IM, Candido D et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 2021; 372:815–821 [View Article] [PubMed]
    [Google Scholar]
  5. Naveca FG, Nascimento V, de Souza VC, Corado A de L, Nascimento F et al. COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence. Nat Med 2021; 27:1230–1238 [View Article] [PubMed]
    [Google Scholar]
  6. Kannan SR, Spratt AN, Cohen AR, Naqvi SH, Chand HS et al. Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses. J Autoimmun 2021; 124:102715 [View Article] [PubMed]
    [Google Scholar]
  7. Sabir JSM, Lam TT-Y, Ahmed MMM, Li L, Shen Y et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 2016; 351:81–84 [View Article] [PubMed]
    [Google Scholar]
  8. Terada Y, Matsui N, Noguchi K, Kuwata R, Shimoda H et al. Emergence of pathogenic coronaviruses in cats by homologous recombination between feline and canine coronaviruses. PLoS One 2014; 9:e106534 [View Article] [PubMed]
    [Google Scholar]
  9. Goldstein SA, Brown J, Pedersen BS, Quinlan AR, Elde NC. Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens. bioRxiv 20212021 [View Article] [PubMed]
    [Google Scholar]
  10. Lau SKP, Li KSM, Huang Y, Shek C-T, Tse H et al. Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events. J Virol 2010; 84:2808–2819 [View Article] [PubMed]
    [Google Scholar]
  11. Zhang Z, Shen L, Gu X. Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission. Sci Rep 2016; 6:25049 [View Article] [PubMed]
    [Google Scholar]
  12. Simon-Loriere E, Holmes EC. Why do RNA viruses recombine?. Nat Rev Microbiol 2011; 9:617–626 [View Article] [PubMed]
    [Google Scholar]
  13. Martin DP, Biagini P, Lefeuvre P, Golden M, Roumagnac P et al. Recombination in eukaryotic single stranded DNA viruses. Viruses 2011; 3:1699–1738 [View Article] [PubMed]
    [Google Scholar]
  14. Francisco R da S Jr, Benites LF, Lamarca AP, de Almeida LGP, Hansen AW et al. Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil. Virus Res 2021; 296:198345 [View Article] [PubMed]
    [Google Scholar]
  15. Zhou HY, Cheng YX, Xu L et al. Genomic Evidence for Divergent Co-infections of SARS-CoV-2 lineages 2021 [View Article]
    [Google Scholar]
  16. Tonkin-Hill G, Martincorena I, Amato R, Lawson AR, Gerstung M et al. Patterns of within-host genetic diversity in SARS-CoV-2. elife 2021; 10:e66857 [View Article] [PubMed]
    [Google Scholar]
  17. Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G et al. SARS-CoV-2 within-host diversity and transmission. Science 2021; 372:eabg0821 [View Article] [PubMed]
    [Google Scholar]
  18. Jackson B, Boni MF, Bull MJ, Colleran A, Colquhoun RM et al. Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic. Cell 2021; 184:5179–5188 [View Article] [PubMed]
    [Google Scholar]
  19. Haddad D, John SE, Mohammad A, Hammad MM, Hebbar P et al. SARS-CoV-2: Possible recombination and emergence of potentially more virulent strains. PLoS One 2021; 16:e0251368 [View Article] [PubMed]
    [Google Scholar]
  20. Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete CA et al. Report 46: factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals. medRxiv 20212021.11.01.21265731 [View Article]
    [Google Scholar]
  21. Nascimento VAD, Corado ALG, Nascimento FOD, Costa Á, Duarte DCG et al. Genomic and phylogenetic characterisation of an imported case of SARS-CoV-2 in Amazonas State, Brazil. Mem Inst Oswaldo Cruz 2020; 115:e200310 [View Article] [PubMed]
    [Google Scholar]
  22. Paiva MHS, Guedes DRD, Docena C, Bezerra MF, Dezordi FZ et al. Multiple introductions followed by ongoing community spread of SARS-cov-2 at one of the largest metropolitan areas of Northeast Brazil. Viruses 2020; 12:E1414 [View Article]
    [Google Scholar]
  23. Resende PC, Motta FC, Roy S et al. SARS-CoV-2 Genomes Recovered by Long Amplicon Tiling Multiplex Approach using Nanopore Sequencing and Applicable to Other Sequencing Platforms 2020 [View Article]
    [Google Scholar]
  24. Dezordi FZ, Campos T de L, Jeronimo PMC et al. ViralFlow: a versatile automated workflow for SARS-CoV-2 genome assembly, lineage assignment, mutations and intrahost variant detection. Viruses 2022; 2:217 [View Article]
    [Google Scholar]
  25. Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 2018; 34:i884–i890 [View Article]
    [Google Scholar]
  26. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article]
    [Google Scholar]
  27. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article] [PubMed]
    [Google Scholar]
  28. Grubaugh ND, Gangavarapu K, Quick J, Matteson NL, De Jesus JG et al. An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar. Genome Biol 2019; 20:8 [View Article] [PubMed]
    [Google Scholar]
  29. Bam-Readcount The McDonnell Genome Institute; 2021 https://github.com/genome/bam-readcount
  30. O’Toole Á, Scher E, Underwood A, Jackson B, Hill V et al. Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool. Virus Evol 2021; 7:veab064 [View Article] [PubMed]
    [Google Scholar]
  31. Aksamentov I, Neher R. Nextclade; 2021 https://clades.nextstrain.org
  32. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES et al. Integrative genomics viewer. Nat Biotechnol 2011; 29:24–26 [View Article] [PubMed]
    [Google Scholar]
  33. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013; 30:772–780 [View Article] [PubMed]
    [Google Scholar]
  34. Hadfield J, Megill C, Bell SM, Huddleston J, Potter B et al. Nextstrain: real-time tracking of pathogen evolution. Bioinformatics 2018; 34:4121–4123 [View Article] [PubMed]
    [Google Scholar]
  35. Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–1659 [View Article] [PubMed]
    [Google Scholar]
  36. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
    [Google Scholar]
  37. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article] [PubMed]
    [Google Scholar]
  38. Simmonds P. Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories. mSphere 2020; 5:e00408-20 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000751
Loading
/content/journal/mgen/10.1099/mgen.0.000751
Loading

Data & Media loading...

Supplements

Loading data from figshare Loading data from figshare

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error