Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka
<p><strong>Background:</strong> 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.</p> <p><strong&g...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Frontiers Media
2022
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| _version_ | 1826310924830507008 |
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| author | Ranasinghe, D Jayathilaka, DJ Jeewandara, C Gunasinghe, D Ariyaratne, D Jayadas, TTP Kuruppu, H Wijesinghe, A Bary, FF Madhusanka, D Pushpakumara, PD Guruge, D Wijayamuni, R Ogg, GS Malavige, GN |
| author_facet | Ranasinghe, D Jayathilaka, DJ Jeewandara, C Gunasinghe, D Ariyaratne, D Jayadas, TTP Kuruppu, H Wijesinghe, A Bary, FF Madhusanka, D Pushpakumara, PD Guruge, D Wijayamuni, R Ogg, GS Malavige, GN |
| author_sort | Ranasinghe, D |
| collection | OXFORD |
| description | <p><strong>Background:</strong> 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.</p>
<p><strong>Methods:</strong> 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.</p>
<p><strong>Results:</strong> 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.</p>
<p><strong>Conclusions:</strong> 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.</p> |
| first_indexed | 2024-03-07T08:00:43Z |
| format | Journal article |
| id | oxford-uuid:959c26bf-59ff-48c9-a19a-b10f8bb3fe0d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:00:43Z |
| publishDate | 2022 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:959c26bf-59ff-48c9-a19a-b10f8bb3fe0d2023-09-26T15:13:15ZMolecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri LankaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:959c26bf-59ff-48c9-a19a-b10f8bb3fe0dEnglishSymplectic ElementsFrontiers Media 2022Ranasinghe, DJayathilaka, DJJeewandara, CGunasinghe, DAriyaratne, DJayadas, TTPKuruppu, HWijesinghe, ABary, FFMadhusanka, DPushpakumara, PDGuruge, DWijayamuni, ROgg, GSMalavige, GN<p><strong>Background:</strong> 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.</p> <p><strong>Methods:</strong> 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.</p> <p><strong>Results:</strong> 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.</p> <p><strong>Conclusions:</strong> 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.</p> |
| spellingShingle | Ranasinghe, D Jayathilaka, DJ Jeewandara, C Gunasinghe, D Ariyaratne, D Jayadas, TTP Kuruppu, H Wijesinghe, A Bary, FF Madhusanka, D Pushpakumara, PD Guruge, D Wijayamuni, R Ogg, GS Malavige, GN Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title | Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title_full | Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title_fullStr | Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title_full_unstemmed | Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title_short | Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka |
| title_sort | molecular epidemiology of ay 28 and ay 104 delta sub lineages in sri lanka |
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