دورية أكاديمية
1064. Intra-Host SARS-CoV-2 Evolution Dynamics
| العنوان: | 1064. Intra-Host SARS-CoV-2 Evolution Dynamics |
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| المؤلفون: | Haddad, Kim El, Esper, Frank, Mudiyanselage, Thamali Madhushani Adhikari, Li, Jing, Zheng, Tu, Cheng, Yu-Wei, Rhoads, Daniel D, Farkas, Daniel H, Ko, Jennifer, Worley, Sarah, Rubin, Brian, Zhang, Xiangyi, Leng, Xiaoyi |
| المصدر: | Open Forum Infectious Diseases ; volume 9, issue Supplement_2 ; ISSN 2328-8957 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Infectious Diseases, Oncology |
| الوصف: | Background Our understanding of SARS-CoV-2 evolution is limited. Most estimates arise from analysis of global databases populated with unrelated sequences and is currently estimated at ∼27.7 substitutions/genome/year. SARS-CoV-2 polymerase contains a proofreading function encoded by NSP-14 limiting change. Additionally, virus evolution may be influenced by patient comorbidity. Intra-host mutational rate (MR) during infection remain poorly studied. Methods To minimize effect of vaccination and/or natural immunity on MR analysis, paired samples from adults originating from the initial pandemic wave (3/17/2020 through 5/27/2020) were retrieved and analyzed at Cleveland Clinic. Viral genome analysis was performed using next generation sequencing, and mutations between paired samples were quantified at allele frequencies (AF) ≥ 0.1, ≥ 0.5 and ≥ 0.75 and compared. MR was calculated employing F81 and JC69 evolution models and compared between isolates with (Δ NSP-14) and without (wildtype, wt) non-synonymous mutations in NSP-14 and by comorbidity. Results A total of 40 patients (80 sample pairs) were identified. Median interval between paired tests was 15 days [range 5-32]. The estimated MR by F81 modeling was 317.2 (95%CI 312.0-322.3), 54.6 (95%CI 52.5-56.7) and 45.1 (95%CI 43.1-47.0) substitutions/genome/year at AF of ≥0.1, ≥0.5, ≥0.75 respectively. Rates in ΔNSP-14 (n=13) vs wt (n=27) groups were 557.7 (95%CI 537.0-578.2) vs 193.1 (95%CI 187.1-199.1) p-value 0.001, 50.8 (95%CI 44.3-57.3) vs 56.3 (95%CI 53.1-59.4) p-value 0.144, and 31.0 (95%CI 25.9-36.1) vs 51.3 (95%CI 48.3-54.3) p- value < 0.001 at AF ≥0.1, ≥0.5, ≥0.75 respectively. Patients with immune comorbidities (n=6) had significantly higher MR of 137.6 (95%CI 114.6-160.5) vs 40.5 (95%CI 38.4-42.7) p-value < 0.001, and 113.7 (95%CI 92.8-134.5) vs 33.4 (95%CI 31.5-35.4) p-value < 0.001 at AF ≥0.5 and ≥0.75 respectively. Similar results were obtained when using the JC69 model. Conclusion Intra-host SARS-CoV-2 mutation rates are ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/ofid/ofac492.905 |
| الإتاحة: | https://doi.org/10.1093/ofid/ofac492.905Test https://academic.oup.com/ofid/article-pdf/9/Supplement_2/ofac492.905/47891377/ofac492.905.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.349A2FC4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ofid/ofac492.905 |
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