Molecular Epidemiology of AY.28 and AY.104 Delta Sub-lineages in Sri Lanka

  1. Diyanath Ranasinghe
  2. Deshni Jayathilaka
  3. Chandima Jeewandara
  4. Dumni Gunasinghe
  5. Dinuka Ariyaratne
  6. Tibutius Thanesh Pramanayagam Jayadas
  7. Heshan Kuruppu
  8. Ayesha Wijesinghe
  9. Fathima Farha Bary
  10. Deshan Madhusanka
  11. Pradeep Darshana Pushpakumara
  12. Dinuka Guruge
  13. Ruwan Wijayamuni
  14. Graham S. Ogg
  15. Gathsaurie Neelika Malavige

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Abstract

The worst SARS-CoV-2 outbreak in Sri Lanka was due to the two Sri Lankan delta sub-lineages AY.28 and AY.104. We proceeded to further characterize the mutations and clinical disease severity of these two sub-lineages.

Methods

705 delta SARS-CoV-2 genomes sequenced by our laboratory from mid-May to November 2021 using Illumina and Oxford Nanopore were included in the analysis. The clinical disease severity of 440/705 individuals were further analyzed to determine if infection with either AY.28 or AY.104 was associated with more severe disease. Sub-genomic RNA (sg-RNA) expression was analyzed using periscope.

Results

AY.28 was the dominant variant throughout the outbreak, accounting for 67.7% of infections during the peak of the outbreak. AY.28 had three lineage defining mutations in the spike protein: A222V (92.80%), A701S (88.06%), and A1078S (92.04%) and seven in the ORF1a: R24C, K634N, P1640L, A2994V, A3209V, V3718A, and T3750I. AY.104 was characterized by the high prevalence of T95I (90.81%) and T572L (65.01%) mutations in the spike protein and by the absence of P1640L (94.28%) in ORF1a with the presence of A1918V (98.58%) mutation. The mean sgRNA expression levels of ORF6 in AY.28 were significantly higher compared to AY.104 ( p < 0.0001) and B.1.617.2 ( p < 0.01). Also, ORF3a showed significantly higher sgRNA expression in AY.28 compared to AY.104 ( p < 0.0001). There was no difference in the clinical disease severity or duration of hospitalization in individuals infected with these sub lineages.

Conclusions

Therefore, AY.28 and AY.104 appear to have a fitness advantage over the parental delta variant (B.1.617.2), while AY.28 also had a higher expression of sg-RNA compared to other sub-lineages. The clinical implications of these should be further investigated.

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  1. Version published to 10.3389/fpubh.2022.873633
  2. ScreenIT

    SciScore for 10.1101/2022.02.05.22270436: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Amino acid mutations and their frequencies for Spike, ORF1a, ORF1b, and N proteins were calculated, and frequencies of ambiguous amino acids derived from ambiguous nucleotides were removed using in-house python scripts.
    python
    suggested: (IPython, RRID:SCR_001658)
    The phylogenetic tree was inferred by Maximum Likelihood in IQ-Tree (version 1.6.12) using the GTR+G model of nucleotide substitution and 1000 replicates of ultrafast bootstrapping (-B 1000) and SH-aLRT branch test (-alrt 1000).
    IQ-Tree
    suggested: (IQ-TREE, RRID:SCR_017254)
    104: The PyMOL Molecular Graphics System v.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    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.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.02.05.22270436 on medRxiv