{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:06:51Z","timestamp":1787112411600,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012918","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000877","name":"Rockefeller Foundation","doi-asserted-by":"publisher","award":["2021 HTH 018"],"award-info":[{"award-number":["2021 HTH 018"]}],"id":[{"id":"10.13039\/100000877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>\nBackground\n<\/jats:title>\n<jats:p>COVID-19 pandemic had unprecedented global impact on health and society, highlighting the need for a detailed understanding of SARS-CoV-2 evolution in response to host and environmental factors. This study investigates the evolution of SARS-CoV-2 via mutation dynamics, focusing on distinct age cohorts, geographical location, and vaccination status within the Indian population, one of the nations most affected by COVID-19.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>\nMethodology\n<\/jats:title>\n<jats:p>Comprehensive dataset, across diverse time points during the Alpha, Delta, and Omicron variant waves, captured essential phases of the pandemic\u2019s footprint in India. By leveraging genomic data from Global Initiative on Sharing Avian Influenza Data (GISAID), we examined the substitution mutation landscape of SARS-CoV-2 in three demographic segments: children (1\u201317 years), working-age adults (18\u201364 years), and elderly individuals (65+ years). A balanced dataset of 69,975 samples was used for the study, comprising 23,325 samples from each group. This design ensured high statistical power, as confirmed by power analysis. We employed bioinformatics and statistical analyses, to explore genetic diversity patterns and substitution frequencies across the age groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>\nPrincipal findings\n<\/jats:title>\n<jats:p>The working-age group exhibited a notably high frequency of unique substitutions, suggesting that immune pressures within highly interactive populations may accelerate viral adaptation. Geographic analysis emphasizes notable regional variation in substitution rates, potentially driven by population density and local transmission dynamics, while regions with more homogeneous strain circulation show relatively lower substitution rates. The analysis also revealed a significant surge in unique substitutions across all age groups during the vaccination period, with substitution rates remaining elevated even after widespread vaccination, compared to pre-vaccination levels. This trend supports the\u00a0virus's\u00a0adaptive response to heightened immune pressures from vaccination, as observed through the increased prevalence of substitutions in important regions of SARS-CoV-2 genome like ORF1ab and Spike, potentially contributing to immune escape and\u00a0transmissibility.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>\nConclusion\n<\/jats:title>\n<jats:p>Our findings affirm the importance of continuous surveillance on viral evolution, particularly in countries with high transmission rates. This research provides insights for anticipating future viral outbreaks and refining pandemic preparedness strategies, thus enhancing our capacity for proactive global health responses.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012918","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T20:08:53Z","timestamp":1741637333000},"page":"e0012918","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["SARS-CoV-2 Alchemy: Understanding the dynamics of age, vaccination, and geography in the evolution of SARS-CoV-2 in India"],"prefix":"10.1371","volume":"19","author":[{"given":"Mansi","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Shamim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umang","family":"Umang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-8327","authenticated-orcid":true,"given":"Rajesh","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"pntd.0012918.ref001","author":"World Health Organization"},{"key":"pntd.0012918.ref002","author":"Centers for Disease Control and Prevention"},{"issue":"9","key":"pntd.0012918.ref003","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S1473-3099(12)70121-4","article-title":"Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study","volume":"12","author":"FS Dawood","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"pntd.0012918.ref004","author":"Centers for Disease Control and Prevention","journal-title":"National Center for Immunization and Respiratory Diseases (NCIRD) [Internet]. 2019 [cited 2024 Sep 22]. 2009 H1N1 Pandemic (H1N1pdm09 virus)"},{"issue":"6","key":"pntd.0012918.ref005","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"PV Markov","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pntd.0012918.ref006","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrmicro.2017.118","article-title":"The evolution of seasonal influenza viruses","volume":"16","author":"VN Petrova","year":"2018","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pntd.0012918.ref007","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12977-018-0395-4","article-title":"HIV evolution and diversity in ART-treated patients","volume":"15","author":"G van Zyl","year":"2018","journal-title":"Retrovirology"},{"key":"pntd.0012918.ref008","doi-asserted-by":"crossref","first-page":"1294699","DOI":"10.3389\/fmed.2023.1294699","article-title":"Unraveling the genetic evolution of SARS-CoV-2 recombinants using mutational dynamics across the different lineages","volume":"10","author":"V Ravi","year":"2023","journal-title":"Frontiers in Medicine"},{"key":"pntd.0012918.ref009","doi-asserted-by":"crossref","first-page":"127099","DOI":"10.1016\/j.micres.2022.127099","article-title":"Mutational dynamics across VOCs in international travellers and community transmission underscores importance of Spike-ACE2 interaction","volume":"262","author":"P Mehta","year":"2022","journal-title":"Microbiol Res"},{"key":"pntd.0012918.ref010","doi-asserted-by":"crossref","first-page":"753648","DOI":"10.3389\/fgene.2021.753648","article-title":"Geographical Landscape and Transmission Dynamics of SARS-CoV-2 Variants Across India: A Longitudinal Perspective","volume":"12","author":"N Jha","year":"2021","journal-title":"Front Genet"},{"key":"pntd.0012918.ref011","doi-asserted-by":"crossref","unstructured":"Li Y, Choudhary MC, Regan J, Boucau J, Nathan A, Speidel T, et al. 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