{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:24:22Z","timestamp":1760232262032,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070922","2020RC016"],"award-info":[{"award-number":["32070922","2020RC016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Universities","award":["32070922","2020RC016"],"award-info":[{"award-number":["32070922","2020RC016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>It has been argued that vaccine-breakthrough infections of SARS-CoV-2 would likely accelerate the emergence of novel variants with immune evasion. This study explored the evolutionary patterns of the Delta variant in countries\/regions with relatively high and low vaccine coverage based on large-scale sequences. Our results showed that (i) the sequences were grouped into two clusters (L and R); the R cluster was dominant, its proportion increased over time and was higher in the high-vaccine-coverage areas; (ii) genetic diversities in the countries\/regions with low vaccine coverage were higher than those in the ones with high vaccine coverage; (iii) unique mutations and co-mutations were detected in different countries\/regions; in particular, common co-mutations were exhibited in highly occurring frequencies in the areas with high vaccine coverage and presented in increasing frequencies over time in the areas with low vaccine coverage; (iv) five sites on the S protein were under strong positive selection in different countries\/regions, with three in non-C to U sites (I95T, G142D and T950N), and the occurring frequencies of I95T in high vaccine coverage areas were higher, while G142D and T950N were potentially immune-pressure-selected sites; and (v) mutation at the N6-methyladenosine site 4 on ORF7a (C27527T, P45L) was detected and might be caused by immune pressure. Our study suggested that certain variation differences existed between countries\/regions with high and low vaccine coverage, but they were not likely caused by host immune pressure. We inferred that no extra immune pressures on SARS-CoV-2 were generated with high vaccine coverage, and we suggest promoting and strengthening the uptake of the COVID-19 vaccine worldwide, especially in less developed areas.<\/jats:p>","DOI":"10.3390\/v14102296","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T22:19:53Z","timestamp":1666217993000},"page":"2296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evolutionary Pattern Comparisons of the SARS-CoV-2 Delta Variant in Countries\/Regions with High and Low Vaccine Coverage"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiahao","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linqian","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2082-2197","authenticated-orcid":false,"given":"Hanli","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanhui","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianglei","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanpeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2988-384X","authenticated-orcid":false,"given":"Jiemei","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-0540","authenticated-orcid":false,"given":"Jinsheng","family":"He","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.medj.2021.06.007","article-title":"FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system","volume":"2","author":"Pawlowski","year":"2021","journal-title":"Med"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s40249-021-00915-3","article-title":"Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: A systematic review and meta-analysis","volume":"10","author":"Liu","year":"2021","journal-title":"Infect. Dis. Poverty"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pormohammad, A., Zarei, M., Ghorbani, S., Mohammadi, M., Razizadeh, M.H., Turner, D.L., and Turner, R.J. (2021). Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Vaccines, 9.","DOI":"10.2139\/ssrn.3812422"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1021\/acs.jcim.1c01451","article-title":"Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance","volume":"62","author":"Chen","year":"2022","journal-title":"J. Chem. Inf. Model"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1016\/S2213-2600(21)00005-9","article-title":"New variant of SARS-CoV-2 in UK causes surge of COVID-19","volume":"9","author":"Kirby","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Reardon, S. (2021). How the Delta variant achieves its ultrafast spread. Nature, Epub ahead of print.","DOI":"10.1038\/d41586-021-01986-w"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41577-021-00662-4","article-title":"SARS-CoV-2 breakthrough infections in vaccinated individuals: Measurement, causes and impact","volume":"22","author":"Lipsitch","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.cell.2020.09.018","article-title":"Molecular Architecture of the SARS-CoV-2 Virus","volume":"183","author":"Yao","year":"2020","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1126\/science.abc8169","article-title":"The emergence of SARS-CoV-2 in Europe and North America","volume":"370","author":"Worobey","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cell.2020.11.020","article-title":"Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity","volume":"184","author":"Volz","year":"2021","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-021-03361-1","article-title":"SARS-CoV-2 spike D614G change enhances replication and transmission","volume":"592","author":"Zhou","year":"2021","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.cell.2021.01.037","article-title":"Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity","volume":"184","author":"Thomson","year":"2021","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1038\/s41467-022-33233-9","article-title":"Increased household transmission and immune escape of the SARS-CoV-2 Omicron compared to Delta variants","volume":"13","author":"Jalali","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1038\/s41467-022-33498-0","article-title":"Household transmission of SARS-CoV-2 Omicron variant of concern subvariants BA.1 and BA.2 in Denmark","volume":"13","author":"Lyngse","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"742167","DOI":"10.3389\/fimmu.2021.742167","article-title":"Implication of SARS-CoV-2 Immune Escape Spike Variants on Secondary and Vaccine Breakthrough Infections","volume":"12","author":"Ahmad","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1016\/S2213-2600(22)00010-8","article-title":"Fourth dose of COVID-19 vaccines in Israel","volume":"10","author":"Burki","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/cid\/ciab070","article-title":"The Case Against Delaying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA Vaccine Boosting Doses","volume":"73","author":"Bieniasz","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/d41586-021-01696-3","article-title":"Delta coronavirus variant: Scientists brace for impact","volume":"595","author":"Callaway","year":"2021","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(21)01358-1","article-title":"SARS-CoV-2 Delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness","volume":"397","author":"Sheikh","year":"2021","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"750725","DOI":"10.3389\/fmicb.2021.750725","article-title":"Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617","volume":"12","author":"Fan","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"vew007","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen)","volume":"2","author":"Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41422-020-00465-7","article-title":"The m(6)A methylome of SARS-CoV-2 in host cells","volume":"31","author":"Liu","year":"2021","journal-title":"Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"Shang","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11850","DOI":"10.1021\/acs.jpclett.1c03380","article-title":"Mechanisms of SARS-CoV-2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America","volume":"12","author":"Wang","year":"2021","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11904-021-00541-6","article-title":"Undernutrition and HIV Infection in Sub-Saharan Africa: Health Outcomes and Therapeutic Interventions","volume":"18","author":"Fuseini","year":"2021","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1056\/NEJMc2031364","article-title":"Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host","volume":"383","author":"Choi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1056\/NEJMsb2104756","article-title":"SARS-CoV-2 Variants in Patients with Immunosuppression","volume":"385","author":"Corey","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/s12276-021-00658-z","article-title":"Mutational spectrum of SARS-CoV-2 during the global pandemic","volume":"53","author":"Yi","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/molbev\/msaa188","article-title":"Evidence for Strong Mutation Bias toward, and Selection against, U Content in SARS-CoV-2: Implications for Vaccine Design","volume":"38","author":"Rice","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41559-020-1124-7","article-title":"Dissimilation of synonymous codon usage bias in virus-host coevolution due to translational selection","volume":"4","author":"Chen","year":"2020","journal-title":"Nat. Ecol. Evol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"nwab220","DOI":"10.1093\/nsr\/nwab220","article-title":"Mutation signatures inform the natural host of SARS-CoV-2","volume":"9","author":"Deng","year":"2022","journal-title":"Natl. Sci. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"evab087","DOI":"10.1093\/gbe\/evab087","article-title":"Mutation Rates and Selection on Synonymous Mutations in SARS-CoV-2","volume":"13","author":"Walker","year":"2021","journal-title":"Genome Biol. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1016\/j.cell.2021.03.029","article-title":"Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein","volume":"184","author":"Suryadevara","year":"2021","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1126\/science.abl9463","article-title":"Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant","volume":"374","author":"Zhang","year":"2021","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"bbab222","DOI":"10.1093\/bib\/bbab222","article-title":"Co-mutation modules capture the evolution and transmission patterns of SARS-CoV-2","volume":"22","author":"Qin","year":"2021","journal-title":"Brief Bioinform"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"703933","DOI":"10.3389\/fmicb.2021.703933","article-title":"Genomic Surveillance and Phylodynamic Analyses Reveal the Emergence of Novel Mutations and Co-mutation Patterns Within SARS-CoV-2 Variants Prevalent in India","volume":"12","author":"Biswas","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/j.cell.2021.04.025","article-title":"Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant","volume":"184","author":"Deng","year":"2021","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41467-022-28324-6","article-title":"Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants","volume":"13","author":"Saville","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41586-021-04245-0","article-title":"The N501Y spike substitution enhances SARS-CoV-2 infection and transmission","volume":"602","author":"Liu","year":"2022","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12985-021-01554-8","article-title":"Impact of the N501Y substitution of SARS-CoV-2 Spike on neutralizing monoclonal antibodies targeting diverse epitopes","volume":"18","author":"Cheng","year":"2021","journal-title":"Virol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2100170118","DOI":"10.1073\/pnas.2100170118","article-title":"2\u2032-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography","volume":"118","author":"Wilamowski","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0366221","DOI":"10.1128\/mbio.03662-21","article-title":"N7-Methylation of the Coronavirus RNA Cap Is Required for Maximal Virulence by Preventing Innate Immune Recognition","volume":"13","author":"Pan","year":"2022","journal-title":"mBio"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nature09489","article-title":"2\u2032-O methylation of the viral mRNA cap evades host restriction by IFIT family members","volume":"468","author":"Daffis","year":"2010","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1038\/s41467-021-23594-y","article-title":"A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2\u2032-O methylation of its first nucleotide","volume":"12","author":"Viswanathan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41590-020-0650-4","article-title":"The RNA modification N(6)-methyladenosine as a novel regulator of the immune system","volume":"21","author":"Shulman","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-021-03681-2","article-title":"Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans","volume":"596","author":"Alter","year":"2021","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2022.02.005","article-title":"Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2","volume":"185","author":"Afkhami","year":"2022","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.chom.2021.06.006","article-title":"SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity","volume":"29","author":"Motozono","year":"2021","journal-title":"Cell Host. Microbe."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eabj6824","DOI":"10.1126\/scitranslmed.abj6824","article-title":"Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity","volume":"14","author":"Riou","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eabj1750","DOI":"10.1126\/sciimmunol.abj1750","article-title":"SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees","volume":"6","author":"Geers","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41577-021-00544-9","article-title":"Concerns about SARS-CoV-2 evolution should not hold back efforts to expand vaccination","volume":"21","author":"Cobey","year":"2021","journal-title":"Nat. Rev. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2296\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:57:10Z","timestamp":1760144230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["v14102296"],"URL":"https:\/\/doi.org\/10.3390\/v14102296","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,10,19]]}}}