{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:26:28Z","timestamp":1788909988148,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The changing state of protective immunity to COVID-19 in the global population in the six years since COVID-19\u2019s origin in 2019 is examined in the context of the (i) circulation of SARS-CoV-2 in the population, (ii) widespread use of different types of COVID-19 vaccines beginning in December 2020 and continuing to the present time, and (iii) ongoing evolution of SARS-CoV-2 to produce mutant viruses with greater infectivity, replication rate, evasion of immunity, and transmissibility. The outlook, and possible vaccine strategies, for the future control of COVID-19 are also examined.<\/jats:p>","DOI":"10.3390\/pathogens14121197","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Perspective Overview of Changing Population Immunity to COVID-19 in the Context of Infection, Vaccination, and Emerging SARS-CoV-2 Variants"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0246-7053","authenticated-orcid":false,"given":"Ranjan","family":"Ramasamy","sequence":"first","affiliation":[{"name":"ID-FISH Technology, 556 Gibraltar Drive, Milpitas, CA 95035, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12910","DOI":"10.1074\/jbc.REV120.013930","article-title":"The molecular virology of coronaviruses","volume":"295","author":"Hartenian","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Papa, G., Mallery, D.L., Albecka, A., Welch, L.G., Cattin-Ortol\u00e1, J., Luptak, J., Paul, D., McMahon, H.T., Goodfellow, I.G., and Carter, A. (2021). Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009246"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ramasamy, R. (2020). Nasal conditioning of inspired air, innate immunity in the respiratory tract and SARS-CoV-2 infectivity. Open Sci. Forum.","DOI":"10.31219\/osf.io\/4j95b"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ramasamy, R. (2021). Perspective of the relationship between the susceptibility to initial SARS-CoV-2 infectivity and optimal nasal conditioning of inhaled air. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157919"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ramasamy, R. (2022). Innate and adaptive immune responses in the upper respiratory tract and the infectivity of SARS-CoV-2. Viruses, 14.","DOI":"10.3390\/v14050933"},{"key":"ref_7","unstructured":"UK Government Green Book (2025, November 18). COVID 19-SARS-CoV-2, Available online: https:\/\/assets.publishing.service.gov.uk\/media\/68b5be03536d629f9c82a97d\/Green-book-chapter-COVID-19_1_9_25.pdf."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1146\/annurev-virology-012420-022445","article-title":"Seasonality of respiratory viral infections","volume":"7","author":"Moriyama","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41467-021-20991-1","article-title":"Assessing the influence of climate on wintertime SARS-CoV-2 outbreaks","volume":"12","author":"Baker","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_10","unstructured":"(2025, September 29). UK Health and Security Agency. 2025. Epidemiology of COVID-19 in England: January 2020 to December 2024, Available online: https:\/\/www.gov.uk\/government\/publications\/epidemiology-of-covid-19-in-england\/epidemiology-of-covid-19-in-england-january-2020-to-december-2024."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41577-020-0308-3","article-title":"COVID-19: Immunopathology and its implications for therapy","volume":"20","author":"Cao","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"Lamers","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"De Neck, S., Penrice-Randal, R., Clark, J.J., Sharma, P., Bentley, E.G., Kirby, A., Mega, D.F., Han, X., Owen, A., and Hiscox, J.A. (2023). The stereotypic response of the pulmonary vasculature to respiratory viral infections: Findings in mouse models of SARS-CoV-2, influenza A and gammaherpesvirus infections. Viruses, 15.","DOI":"10.3390\/v15081637"},{"key":"ref_15","unstructured":"World Health Organization (2023, October 04). Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int."},{"key":"ref_16","unstructured":"World Health Organization Emergency Committee (2025, October 08). Statement on the Second Meeting of the International Health Regulations Emergency Committee Regarding the Outbreak of Novel Coronavirus (2019-nCoV). Available online: https:\/\/www.who.int\/news\/item\/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)."},{"key":"ref_17","unstructured":"World Health Organization (2025, October 08). Coronavirus Disease 2019 (COVID-19) Situation Report\u201451. Available online: https:\/\/www.who.int\/docs\/default-source\/coronaviruse\/situation-reports\/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57)."},{"key":"ref_18","unstructured":"World Health Organization Emergency Committee (2025, October 04). Statement on the Fifteenth Meeting of the International Health Regulations (2005) Emergency Committee on the COVID-19 Pandemic. Available online: https:\/\/www.who.int\/news-room\/speeches\/item\/who-director-general-s-opening-remarks-at-the-media-briefing---5-may-2023."},{"key":"ref_19","unstructured":"World Health Organization (2025, October 04). WHO COVID-19 Dashboard. Available online: https:\/\/data.who.int\/dashboards\/covid19\/data."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ramasamy, R. (2023). COVID-19 vaccines for optimizing immunity in the upper respiratory tract. Viruses, 15.","DOI":"10.20944\/preprints202310.0678.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41577-021-00578-z","article-title":"Immunological mechanisms of vaccine-induced protection against COVID-19 in humans","volume":"21","author":"Sadarangani","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zasada, A.A., Darlinska, A., Wiatrzyk, A., Woznica, K., Forminska, K., Czajka, U., G\u0142\u00f3wka, M., Lis, K., and G\u00f3rska, P. (2023). COVID-19 Vaccines over three years after the outbreak of the COVID-19 Epidemic. Viruses, 15.","DOI":"10.3390\/v15091786"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Plans-Rubi\u00f3, P. (2022). Percentages of vaccination coverage required to establish herd immunity against SARS-CoV-2. Vaccines, 10.","DOI":"10.20944\/preprints202204.0247.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41541-023-00654-6","article-title":"Mucosal vaccines for SARS-CoV-2: Scientific gaps and opportunities\u2014Workshop report","volume":"8","author":"Knisely","year":"2023","journal-title":"NPJ Vaccines"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127602","DOI":"10.1016\/j.vaccine.2025.127602","article-title":"Mucosal COVID-19 vaccines in clinical development","volume":"63","author":"Tscherne","year":"2025","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-025-08910-6","article-title":"Nasal vaccines for respiratory infections","volume":"641","author":"Kiyono","year":"2025","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S1473-3099(22)00320-6","article-title":"Global impact of the first year of COVID-19 vaccination: A mathematical modelling study","volume":"22","author":"Watson","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yamana, T.K., Galanti, M., Pei, S., Di Fusco, M., Angulo, F.J., Moran, M.M., Khan, F., Swerdlow, D.L., and Shaman, J. (2023). The impact of COVID-19 vaccination in the US: Averted burden of SARS-CoV-2-related cases, hospitalizations and deaths. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0275699"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1473-3099(21)00566-1","article-title":"Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer\u2013BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: A retrospective surveillance study","volume":"22","author":"Haas","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4103\/ijmr.ijmr_2591_22","article-title":"Overview of immunological and virological factors driving the evolution and global spread of SARS-CoV-2 variants","volume":"158","author":"Ramasamy","year":"2023","journal-title":"Indian J. Med. Res."},{"key":"ref_31","unstructured":"Institute for Health Metrics and Evaluation (2025, October 02). COVID-19 Model Update: Omicron and Waning Immunity. Available online: https:\/\/www.healthdata.org\/research-analysis\/diseases-injuries\/covid\/covid-19-model-update-omicron-and-waning-immunity."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.1038\/s41467-024-51973-8","article-title":"Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants","volume":"15","author":"Yang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Abbad, A., Lerman, B., Ehrenhaus, J., Monahan, B., Singh, G., Wilson, A., Slamanig, S., Aracena, A., Lyttle, N., and Nardulli, J. (2025). Antibody responses to SARS-CoV-2 variants LP.8.1, LF.7.1, NB.1.8.1, XFG and BA.3.2 following KP.2 monovalent mRNA vaccination. Medrxiv.","DOI":"10.1101\/2025.08.24.25333689"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12985-025-02737-3","article-title":"Immune evasion, infectivity, and membrane fusion of the SARS-CoV-2 JN.1 variant","volume":"22","author":"Tang","year":"2025","journal-title":"Virol. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41590-024-02051-0","article-title":"T cell immune evasion by SARS-CoV-2 JN.1 escapees targeting two cytotoxic T cell epitope hotspots","volume":"26","author":"Tian","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/emph\/eoac010","article-title":"Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution","volume":"10","author":"Amicone","year":"2022","journal-title":"Evol. Med. Public Health"},{"key":"ref_38","unstructured":"(2025, October 08). Global Initiative on Sharing All Influenza Data (GISAID). Available online: https:\/\/gisaid.org\/phylodynamics\/global\/."},{"key":"ref_39","unstructured":"World Health Organization (2025, October 04). Updated Working Definitions and Primary Actions for SARS-CoV-2 Variants. Available online: https:\/\/www.who.int\/publications\/m\/item\/updated-working-definitions-and-primary-actions-for--sars-cov-2-variants."},{"key":"ref_40","unstructured":"Centers for Disease Control and Prevention (2025, October 04). COVID, Available online: https:\/\/www.cdc.gov\/covid\/php\/variants\/variants-and-genomic-surveillance.html."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e374","DOI":"10.1016\/S1473-3099(25)00308-1","article-title":"Antigenic and virological characteristics of SARS-CoV-2 variants BA.3.2, XFG, and NB.1.8.1","volume":"25","author":"Guo","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_42","unstructured":"UK Health Security Agency (2025, October 06). National Flu and COVID-19 Surveillance Report: 25 September 2025 (Week 39), Available online: https:\/\/www.gov.uk\/government\/statistics\/national-flu-and-covid-19-surveillance-reports-2025-to-2026-season\/national-flu-and-covid-19-surveillance-report-25-september-2025-week-39."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shah, J., Liu, S., Potula, H.H., Bhargava, P., Cruz, I., Force, D., Bazerbashi, A., and Ramasamy, R. (2021). IgG and IgM antibody formation to spike and nucleocapsid proteins in COVID-19 characterized by multiplex immunoblot assays. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06031-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1002\/jmv.27688","article-title":"Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review","volume":"94","author":"Notarte","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"126966","DOI":"10.1016\/j.vaccine.2025.126966","article-title":"Durability of COVID-19 vaccine and infection induced immunity: A systematic review and meta-regression analysis","volume":"54","author":"Moore","year":"2025","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e743","DOI":"10.1093\/infdis\/jiaf007","article-title":"Effectiveness of mRNA COVID-19 vaccines and hybrid immunity in preventing SARS-CoV-2 infection and symptomatic COVID-19 among adults in the United States","volume":"231","author":"Feldstein","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Klaassen, F., Swartwood, N.A., Chitwood, M.H., Lopes, R., Haraguchi, M., Salomon, J.A., Cohen, T., and Menzies, N.A. (2025). National- and state-level SARS-CoV-2 immunity trends from January 2020 to December 2023: A mathematical modeling analysis. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiaf532"},{"key":"ref_48","unstructured":"National Health Service (2025, October 08). The COVID-19 Vaccine. Available online: https:\/\/www.nhs.uk\/vaccinations\/covid-19-vaccine\/."},{"key":"ref_49","unstructured":"(2025, October 08). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/other\/ema-recommendation-update-antigenic-composition-authorised-covid-19-vaccines-2025-2026_en.pdf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41586-021-04186-8","article-title":"Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2","volume":"601","author":"Swadling","year":"2022","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e0204924","DOI":"10.1128\/jvi.02049-24","article-title":"A comprehensive review of current insights into the virulence factors of SARS-CoV-2","volume":"99","author":"Wang","year":"2025","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bilev, E., Wild, N., Momayyezi, P., Sala, B.M., Sun, R., Sandalova, T., Marquardt, N., Ljunggren, H.G., Achour, A., and Hammer, Q. (2024). Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012755"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Abay, Z., Sadikaliyeva, S., Nurpeisova, A., Jekebekov, K., Shorayeva, K., Yespembetov, B., Nurabayev, S., Kerimbayev, A., Khairullin, B., and Yoo, H. (2024). Breaking the barrier: SARS-CoV-2 infections in wild and companion animals and their show implications for public health. Viruses, 16.","DOI":"10.3390\/v16060956"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1126\/science.1176225","article-title":"Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans","volume":"325","author":"Garten","year":"2009","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus","volume":"182","author":"Korber","year":"2020","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00430-022-00760-7","article-title":"Intrinsic D614G and P681R\/H mutations in SARS-CoV-2 VoCs alpha, delta, omicron and viruses with D614G plus key signature mutations in spike protein alters fusogenicity and infectivity","volume":"212","author":"Khatri","year":"2023","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1126\/science.abe8499","article-title":"SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo","volume":"370","author":"Hou","year":"2020","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41586-020-2895-3","article-title":"Spike mutation D614G alters SARS-CoV-2 fitness","volume":"592","author":"Plante","year":"2021","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cell.2020.09.032","article-title":"Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant","volume":"183","author":"Yurkovetskiy","year":"2020","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2002106","DOI":"10.2807\/1560-7917.ES.2020.26.1.2002106","article-title":"Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020","volume":"26","author":"Leung","year":"2021","journal-title":"Euro. Surveill."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"109292","DOI":"10.1016\/j.celrep.2021.109292","article-title":"Recurrent emergence of SARS-CoV-2 spike deletion H69\/V70 and its role in the Alpha variant B.1.1.7","volume":"35","author":"Meng","year":"2021","journal-title":"Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41591-021-01270-4","article-title":"Neutralization of SARS-CoV-2 spike 69\/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera","volume":"27","author":"Xie","year":"2021","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sarkar, P., Banerjee, S., Saha, S.A., Mitra, P., and Sarkar, S. (2023). Genome surveillance of SARS-CoV-2 variants and their role in pathogenesis focusing on second wave of COVID-19 in India. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30815-5"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100583","DOI":"10.1016\/j.xcrm.2022.100583","article-title":"Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA","volume":"3","author":"Earnest","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_66","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_67","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_68","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41586-021-04266-9","article-title":"Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation","volume":"602","author":"Saito","year":"2022","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1473-3099(21)00475-8","article-title":"Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: A cohort study","volume":"22","author":"Twohig","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1002\/jmv.27461","article-title":"Variants of concern responsible for SARS-CoV-2 vaccine breakthrough infections from India","volume":"94","author":"Singh","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1038\/s41564-022-01235-4","article-title":"SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope","volume":"7","author":"He","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1038\/s41591-022-01911-2","article-title":"Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa","volume":"28","author":"Tegally","year":"2022","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-022-04474-x","article-title":"Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity","volume":"603","author":"Meng","year":"2022","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-05697-2","article-title":"Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/S1473-3099(22)00663-6","article-title":"Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies","volume":"22","author":"Sheward","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41579-022-00809-7","article-title":"SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies","volume":"21","author":"Cox","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_77","first-page":"521","article-title":"Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution","volume":"614","author":"Cao","year":"2023","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.cell.2022.06.005","article-title":"Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum","volume":"185","author":"Tuekprakhon","year":"2022","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S1473-3099(22)00816-7","article-title":"Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB","volume":"23","author":"Uraki","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_80","first-page":"162","article-title":"SARS-CoV-2 variant biology: Immune escape, transmission and fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41586-022-05482-7","article-title":"Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents","volume":"612","author":"Uraki","year":"2022","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1038\/s41591-022-01887-z","article-title":"Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1\/BA.1.1 or BA.2 subvariant infection in Southern California","volume":"28","author":"Lewnard","year":"2022","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/s41467-023-37051-5","article-title":"Association of SARS-CoV-2 BA.4\/BA.5 Omicron lineages with immune escape and clinical outcome","volume":"14","author":"Lewnard","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s41586-022-04835-6","article-title":"The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle","volume":"606","author":"Ricciardi","year":"2022","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/s41418-021-00916-7","article-title":"SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1","volume":"29","author":"Sun","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Alfi, O., Hamdan, M., Wald, O., Yakirevitch, A., Wandel, O., Oiknine-Djian, E., Gvili, B., Knoller, H., Rozendorn, N., and Golan Berman, H. (2022). SARS-CoV-2 Omicron induces enhanced mucosal interferon response compared to other variants of concern, associated with restricted replication in human lung tissues. Viruses, 14.","DOI":"10.3390\/v14071583"},{"key":"ref_87","first-page":"20499361251314763","article-title":"The JN.1 variant of COVID-19: Immune evasion, transmissibility, and implications for global health","volume":"12","author":"Siddiqui","year":"2025","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41467-025-55938-3","article-title":"Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology","volume":"16","author":"Wickenhagen","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_89","unstructured":"World Health Organization (2025, November 14). Risk Evaluation for SARS-CoV-2 Variant Under Monitoring: XFG. Available online: https:\/\/www.who.int\/publications\/m\/item\/risk-evaluation-for-sars-cov-2-variant-under-monitoring-xfg."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Plans-Rubi\u00f3, P. (2023). Effectiveness of adapted COVID-19 vaccines and ability to establish herd immunity against omicron BA.1 and BA.4-5 variants of SARS-CoV-2. Vaccines, 11.","DOI":"10.3390\/vaccines11121836"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Plans-Rubi\u00f3, P. (2024). What COVID-19 vaccination strategy should be implemented and which vaccines should be used in the post-pandemic era?. Vaccines, 12.","DOI":"10.3390\/vaccines12101180"},{"key":"ref_92","unstructured":"(2025, November 18). UK Government Green Book. Chapter 19. Influenza, Available online: https:\/\/assets.publishing.service.gov.uk\/media\/6838317b5150d70c85aafab9\/Green-book-chapter-19-influenza-28May2025.pdf."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev-immunol-101721-061120","article-title":"T Cell Responses to SARS-CoV-2","volume":"41","author":"Sette","year":"2023","journal-title":"Annu. Rev. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41541-025-01165-2","article-title":"Live attenuated SARS-CoV-2 vaccine OTS-228 demonstrates efficacy, safety, and stability in preclinical model","volume":"10","author":"Britzke","year":"2025","journal-title":"NPJ Vaccines"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"RP97532","DOI":"10.7554\/eLife.97532.3","article-title":"Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms","volume":"13","author":"Okamura","year":"2025","journal-title":"eLife"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ye, Z.W., Ong, C.P., Cao, H., Tang, K., Gray, V.S., Hinson Cheung, P.H., Wang, J., Li, W., Zhang, H., and Luo, P. (2025). A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a. eBioMedicine, 114.","DOI":"10.1016\/j.ebiom.2025.105662"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"eadw0896","DOI":"10.1126\/sciadv.adw0896","article-title":"Safety and immunogenicity of intranasal parainfluenza virus type 5 (PIV5)-vectored COVID-19 vaccine in adults and teens in an open-label phase 1 trial","volume":"11","author":"Spearman","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6000","DOI":"10.1038\/s41467-025-60726-0","article-title":"Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: An open-label, multi-arm phase 1 clinical trial","volume":"16","author":"Jeyanathan","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_99","unstructured":"UK Health Security Agency (2025, November 19). National Flu and COVID-19 Surveillance Report: 6 November 2025 (Week 45), Available online: https:\/\/www.gov.uk\/government\/statistics\/national-flu-and-covid-19-surveillance-reports-2025-to-2026-season\/national-flu-and-covid-19-surveillance-report-6-november-2025-week-45."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"100939","DOI":"10.1016\/j.lanmic.2024.07.002","article-title":"Global wastewater surveillance for pathogens with pandemic potential: Opportunities and challenges","volume":"6","author":"Grassly","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12560-024-09616-0","article-title":"Harnessing the power of next-generation sequencing in wastewater-based epidemiology and global disease surveillance","volume":"17","author":"Farkas","year":"2024","journal-title":"Food Environ. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40246-025-00725-w","article-title":"Establishing a European wastewater pathogen monitoring network employing aviation samples: A proof of concept","volume":"19","author":"Morfino","year":"2025","journal-title":"Hum. Genom."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7999","DOI":"10.1038\/s41467-024-51924-3","article-title":"Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections","volume":"15","author":"Nooruzzaman","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1186\/s12967-025-07076-z","article-title":"Extensive cross-reactive T cell epitopes across SARS-CoV-2 Omicron variant spikes with finite immune evasion mutations","volume":"23","author":"Gan","year":"2025","journal-title":"J. Transl. Med."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/12\/1197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:33:26Z","timestamp":1763976806000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/12\/1197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":104,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["pathogens14121197"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14121197","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]}}}