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Annual Review of Immunology

Volume 43, 2025

SARS-CoV-2: The Interplay Between Evolution and Host Immunity

  • James Brett Case1, Shilpi Jain2,3, Mehul S. Suthar2,3 and Michael S. Diamond1,4
  • 1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; email: [email protected] 2Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA 3Emory Vaccine Center, Emory National Primate Research Center, Atlanta, Georgia, USA 4Department of Pathology & Immunology; Department of Molecular Microbiology; and Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, USA
  • Vol. 43:29-55 (Volume publication date April 2025)
  • First published as a Review in Advance on December 20, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

The persistence of SARS-CoV-2 infections at a global level reflects the repeated emergence of variant strains encoding unique constellations of mutations. These variants have been generated principally because of a dynamic host immune landscape, the countermeasures deployed to combat disease, and selection for enhanced infection of the upper airway and respiratory transmission. The resulting viral diversity creates a challenge for vaccination efforts to maintain efficacy, especially regarding humoral aspects of protection. Here, we review our understanding of how SARS-CoV-2 has evolved during the pandemic, the immune mechanisms that confer protection, and the impact viral evolution has had on transmissibility and adaptive immunity elicited by natural infection and/or vaccination. Evidence suggests that SARS-CoV-2 evolution initially selected variants with increased transmissibility but currently is driven by immune escape. The virus likely will continue to drift to maintain fitness until countermeasures capable of disrupting transmission cycles become widely available.

Keyword(s): evolution, immunity, protection, SARS-CoV-2, vaccines, variants
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2025-04-25
2025-06-15
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Literature Cited

  1. 1.
    Ahn JH, Kim J, Hong SP, Choi SY, Yang MJ, et al. 2021.. Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19. . J. Clin. Investig. 131::e148517
     [Crossref] [Google Scholar]
  2. 2.
    Jayaweera M, Perera H, Gunawardana B, Manatunge J. 2020.. Transmission of COVID-19 virus by droplets and aerosols: a critical review on the unresolved dichotomy. . Environ. Res. 188::109819
     [Crossref] [Google Scholar]
  3. 3.
    Lamers MM, Haagmans BL. 2022.. SARS-CoV-2 pathogenesis. . Nat. Rev. Microbiol. 20::270–84
     [Crossref] [Google Scholar]
  4. 4.
    Jackson CB, Farzan M, Chen B, Choe H. 2022.. Mechanisms of SARS-CoV-2 entry into cells. . Nat. Rev. Mol. Cell Biol. 23::3–20
     [Crossref] [Google Scholar]
  5. 5.
    Fraser R, Orta-Resendiz A, Mazein A, Dockrell DH. 2023.. Upper respiratory tract mucosal immunity for SARS-CoV-2 vaccines. . Trends Mol. Med. 29::255–67
     [Crossref] [Google Scholar]
  6. 6.
    Steiner S, Kratzel A, Barut GT, Lang RM, Aguiar Moreira E, et al. 2024.. SARS-CoV-2 biology and host interactions. . Nat. Rev. Microbiol. 22::206–25
     [Crossref] [Google Scholar]
  7. 7.
    Lauring AS, Frydman J, Andino R. 2013.. The role of mutational robustness in RNA virus evolution. . Nat. Rev. Microbiol. 11::327–36
     [Crossref] [Google Scholar]
  8. 8.
    Smith EC, Sexton NR, Denison MR. 2014.. Thinking outside the triangle: replication fidelity of the largest RNA viruses. . Annu. Rev. Virol. 1::111–32
     [Crossref] [Google Scholar]
  9. 9.
    Kunkel TA. 2004.. DNA replication fidelity. . J. Biol. Chem. 279::16895–98
     [Crossref] [Google Scholar]
  10. 10.
    Duchene S, Featherstone L, Haritopoulou-Sinanidou M, Rambaut A, Lemey P, Baele G. 2020.. Temporal signal and the phylodynamic threshold of SARS-CoV-2. . Virus Evol. 6::veaa061
     [Crossref] [Google Scholar]
  11. 11.
    Ghafari M, du Plessis L, Raghwani J, Bhatt S, Xu B, et al. 2022.. Purifying selection determines the short-term time dependency of evolutionary rates in SARS-CoV-2 and pH1N1 influenza. . Mol. Biol. Evol. 39::msac009
     [Crossref] [Google Scholar]
  12. 12.
    Markov PV, Ghafari M, Beer M, Lythgoe K, Simmonds P, et al. 2023.. The evolution of SARS-CoV-2. . Nat. Rev. Microbiol. 21::361–79
     [Crossref] [Google Scholar]
  13. 13.
    Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, et al. 2020.. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. . Cell 182::812–27.e19
     [Crossref] [Google Scholar]
  14. 14.
    Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, et al. 2021.. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. . Science 372::eabg3055
     [Crossref] [Google Scholar]
  15. 15.
    Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, et al. 2021.. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. . Science 372::815–21
     [Crossref] [Google Scholar]
  16. 16.
    Shen X, Tang H, McDanal C, Wagh K, Fischer W, et al. 2021.. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. . Cell Host Microbe 29::529–39.e3
     [Crossref] [Google Scholar]
  17. 17.
    Dhar MS, Marwal R, Vs R, Ponnusamy K, Jolly B, et al. 2021.. Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. . Science 374::995–99
     [Crossref] [Google Scholar]
  18. 18.
    Mullick B, Magar R, Jhunjhunwala A, Barati Farimani A. 2021.. Understanding mutation hotspots for the SARS-CoV-2 spike protein using Shannon Entropy and K-means clustering. . Comput. Biol. Med. 138::104915
     [Crossref] [Google Scholar]
  19. 19.
    Gayvert K, McKay S, Lim WK, Baum A, Kyratsous C, et al. 2023.. Evolutionary trajectory of SARS-CoV-2 genome shifts during widespread vaccination and emergence of Omicron variant. . NPJ Viruses 1::5
     [Crossref] [Google Scholar]
  20. 20.
    Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, et al. 2021.. Detection of a SARS-CoV-2 variant of concern in South Africa. . Nature 592::438–43
     [Crossref] [Google Scholar]
  21. 21.
    Roemer C, Sheward DJ, Hisner R, Gueli F, Sakaguchi H, et al. 2023.. SARS-CoV-2 evolution in the Omicron era. . Nat. Microbiol. 8::1952–59
     [Crossref] [Google Scholar]
  22. 22.
    Cao Y, Jian F, Wang J, Yu Y, Song W, et al. 2023.. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. . Nature 614::521–29
     [Google Scholar]
  23. 23.
    Sheward DJ, Kim C, Fischbach J, Sato K, Muschiol S, et al. 2022.. Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies. . Lancet Infect. Dis. 22::1538–40
     [Crossref] [Google Scholar]
  24. 24.
    Hadfield J, Megill C, Bell SM, Huddleston J, Potter B, et al. 2018.. Nextstrain: real-time tracking of pathogen evolution. . Bioinformatics 34::4121–23
     [Crossref] [Google Scholar]
  25. 25.
    Islam A, Ferdous J, Sayeed MA, Islam S, Kaisar Rahman M, et al. 2021.. Spatial epidemiology and genetic diversity of SARS-CoV-2 and related coronaviruses in domestic and wild animals. . PLOS ONE 16::e0260635
     [Crossref] [Google Scholar]
  26. 26.
    Dall Schmidt T, Mitze T. 2022.. SARS-CoV-2 outbreaks on Danish mink farms and mitigating public health interventions. . Eur. J. Public Health 32::151–57
     [Crossref] [Google Scholar]
  27. 27.
    Enserink M. 2020.. Coronavirus rips through Dutch mink farms, triggering culls. . Science 368::1169
     [Crossref] [Google Scholar]
  28. 28.
    Larsen HD, Fonager J, Lomholt FK, Dalby T, Benedetti G, et al. 2021.. Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020. . Euro Surveill. 26::2100009
     [Crossref] [Google Scholar]
  29. 29.
    Jahid MJ, Bowman AS, Nolting JM. 2024.. SARS-CoV-2 outbreaks on mink farms—a review of current knowledge on virus infection, spread, spillover, and containment. . Viruses 16::81
     [Crossref] [Google Scholar]
  30. 30.
    Bayarri-Olmos R, Rosbjerg A, Johnsen LB, Helgstrand C, Bak-Thomsen T, et al. 2021.. The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization. . J. Biol. Chem. 296::100536
     [Crossref] [Google Scholar]
  31. 31.
    Hoffmann M, Zhang L, Krüger N, Graichen L, Kleine-Weber H, et al. 2021.. SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization. . Cell Rep. 35::109017
     [Crossref] [Google Scholar]
  32. 32.
    Jones JM, Manrique IM, Stone MS, Grebe E, Saa P, et al. 2023.. Estimates of SARS-CoV-2 seroprevalence and incidence of primary SARS-CoV-2 infections among blood donors, by COVID-19 vaccination status—United States, April 2021–September 2022. . MMWR Morb. Mortal. Wkly. Rep. 72::601–5
     [Crossref] [Google Scholar]
  33. 33.
    Bobrovitz N, Ware H, Ma X, Li Z, Hosseini R, et al. 2023.. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression. . Lancet Infect. Dis. 23::556–67
     [Crossref] [Google Scholar]
  34. 34.
    Ekstrom N, Leino TM, Juutinen A, Lehtonen T, Haveri A, et al. 2024.. Hybrid immunity improves the immune response after the fourth COVID-19 vaccine dose in individuals with medical conditions predisposing to severe COVID-19. . Vaccines 12::247
     [Crossref] [Google Scholar]
  35. 35.
    Spinardi JR, Srivastava A. 2023.. Hybrid immunity to SARS-CoV-2 from infection and vaccination—evidence synthesis and implications for new COVID-19 vaccines. . Biomedicines 11::370
     [Crossref] [Google Scholar]
  36. 36.
    Diamond MS, Kanneganti TD. 2022.. Innate immunity: the first line of defense against SARS-CoV-2. . Nat. Immunol. 23::165–76
     [Crossref] [Google Scholar]
  37. 37.
    Su HC, Jing H, Zhang Y, Members of the COVID Human Genetic Effort, Casanova JL. 2023.. Interfering with interferons: a critical mechanism for critical COVID-19 pneumonia. . Annu. Rev. Immunol. 41::561–85
     [Crossref] [Google Scholar]
  38. 38.
    Suthar MS, Zimmerman MG, Kauffman RC, Mantus G, Linderman SL, et al. 2020.. Rapid generation of neutralizing antibody responses in COVID-19 patients. . Cell Rep. Med. 1::100040
     [Crossref] [Google Scholar]
  39. 39.
    Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, et al. 2021.. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. . Science 371::eabf4063
     [Crossref] [Google Scholar]
  40. 40.
    Mantus G, Nyhoff LE, Edara VV, Zarnitsyna VI, Ciric CR, et al. 2022.. Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination. . Cell Rep. Med. 3::100603
     [Crossref] [Google Scholar]
  41. 41.
    Di Chiara C, Cantarutti A, Costenaro P, Donà D, Bonfante F, et al. 2022.. Long-term immune response to SARS-CoV-2 infection among children and adults after mild infection. . JAMA Netw. Open 5::e2221616
     [Crossref] [Google Scholar]
  42. 42.
    Chen X, Pan Z, Yue S, Yu F, Zhang J, et al. 2020.. Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19. . Signal Transduct. Target. Ther. 5::180
     [Crossref] [Google Scholar]
  43. 43.
    Garcia-Beltran WF, Lam EC, Astudillo MG, Yang D, Miller TE, et al. 2021.. COVID-19-neutralizing antibodies predict disease severity and survival. . Cell 184::476–88.e11
     [Crossref] [Google Scholar]
  44. 44.
    Cohen KW, Linderman SL, Moodie Z, Czartoski J, Lai L, et al. 2021.. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. . Cell Rep. Med. 2::100354
     [Crossref] [Google Scholar]
  45. 45.
    L'Huillier AG, Meyer B, Andrey DO, Arm-Vernez I, Baggio S, et al. 2021.. Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study. . Clin. Microbiol. Infect. 27::784.e1–8
     [Crossref] [Google Scholar]
  46. 46.
    Tan Y, Liu F, Xu X, Ling Y, Huang W, et al. 2020.. Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection. . Front. Med. 14::746–51
     [Crossref] [Google Scholar]
  47. 47.
    Carreno JM, Mendu DR, Simon V, Shariff MA, Singh G, et al. 2021.. Longitudinal analysis of severe acute respiratory syndrome coronavirus 2 seroprevalence using multiple serology platforms. . iScience 24::102937
     [Crossref] [Google Scholar]
  48. 48.
    Grandjean L, Saso A, Torres Ortiz A, Lam T, Hatcher J, et al. 2022.. Long-term persistence of spike protein antibody and predictive modeling of antibody dynamics after infection with severe acute respiratory syndrome coronavirus 2. . Clin. Infect. Dis. 74::1220–29
     [Crossref] [Google Scholar]
  49. 49.
    Joshi D, Nyhoff LE, Zarnitsyna VI, Moreno A, Manning K, et al. 2023.. Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults. . iScience 26::107967
     [Crossref] [Google Scholar]
  50. 50.
    Wimmers F, Burrell AR, Feng Y, Zheng H, Arunachalam PS, et al. 2023.. Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth. . Cell 186::4632–51.e23
     [Crossref] [Google Scholar]
  51. 51.
    Azeem MI, Nooka AK, Shanmugasundaram U, Cheedarla N, Potdar S, et al. 2023.. Impaired SARS-CoV-2 variant neutralization and CD8+ T-cell responses following 3 doses of mRNA vaccines in myeloma: correlation with breakthrough infections. . Blood Cancer Discov. 4::106–17
     [Crossref] [Google Scholar]
  52. 52.
    Chang A, Akhtar A, Lai L, Orellana-Noia VM, Linderman SL, et al. 2022.. Antibody binding and neutralization of live SARS-CoV-2 variants including BA.4/5 following booster vaccination of patients with B-cell malignancies. . Cancer Res. Commun. 2::1684–92
     [Crossref] [Google Scholar]
  53. 53.
    Chang A, Akhtar A, Linderman SL, Lai L, Orellana-Noia VM, et al. 2022.. Humoral responses against SARS-CoV-2 and variants of concern after mRNA vaccines in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. . J. Clin. Oncol. 40::3020–31
     [Crossref] [Google Scholar]
  54. 54.
    Chang A, Koff JL, Lai L, Orellana-Noia VM, Surati M, et al. 2023.. Low neutralizing activity of AZD7442 against current SARS-CoV-2 Omicron variants in patients with B-cell malignancies. . Blood Adv. 7::2459–62
     [Crossref] [Google Scholar]
  55. 55.
    Valanparambil RM, Carlisle J, Linderman SL, Akthar A, Millett RL, et al. 2022.. Antibody response to COVID-19 mRNA vaccine in patients with lung cancer after primary immunization and booster: reactivity to the SARS-CoV-2 WT virus and Omicron variant. . J. Clin. Oncol. 40::3808–16
     [Crossref] [Google Scholar]
  56. 56.
    Valanparambil RM, Lai L, Johns MA, Davis-Gardner M, Linderman SL, et al. 2023.. BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer. . NPJ Vaccines 8::179
     [Crossref] [Google Scholar]
  57. 57.
    Kunkel EJ, Butcher EC. 2003.. Plasma-cell homing. . Nat. Rev. Immunol. 3::822–29
     [Crossref] [Google Scholar]
  58. 58.
    Xu B, Wagner N, Pham LN, Magno V, Shan Z, et al. 2003.. Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1 adhesion pathways. . J. Exp. Med. 197::1255–67
     [Crossref] [Google Scholar]
  59. 59.
    Bertrand Y, Sánchez-Montalvo A, Hox V, Froidure A, Pilette C. 2023.. IgA-producing B cells in lung homeostasis and disease. . Front. Immunol. 14::1117749
     [Crossref] [Google Scholar]
  60. 60.
    Havervall S, Marking U, Svensson J, Greilert-Norin N, Bacchus P, et al. 2022.. Anti-spike mucosal IgA protection against SARS-CoV-2 Omicron infection. . N. Engl. J. Med. 387::1333–36
     [Crossref] [Google Scholar]
  61. 61.
    Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, et al. 2021.. IgA dominates the early neutralizing antibody response to SARS-CoV-2. . Sci. Transl. Med. 13::eabd2223
     [Crossref] [Google Scholar]
  62. 62.
    Sajadi MM, Myers A, Logue J, Saadat S, Shokatpour N, et al. 2022.. Mucosal and systemic responses to severe acute respiratory syndrome coronavirus 2 vaccination determined by severity of primary infection. . mSphere 7::e00279-22
     [Crossref] [Google Scholar]
  63. 63.
    Puhach O, Bellon M, Adea K, Bekliz M, Hosszu-Fellous K, et al. 2023.. SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses. . eBioMedicine 98::104893
     [Crossref] [Google Scholar]
  64. 64.
    Marking U, Bladh O, Havervall S, Svensson J, Greilert-Norin N, et al. 2023.. 7-month duration of SARS-CoV-2 mucosal immunoglobulin-A responses and protection. . Lancet Infect. Dis. 23::150–52
     [Crossref] [Google Scholar]
  65. 65.
    Liew F, Talwar S, Cross A, Willett BJ, Scott S, et al. 2023.. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. . eBioMedicine 87::104402
     [Crossref] [Google Scholar]
  66. 66.
    Mitsi E, Diniz MO, Reiné J, Collins AM, Robinson RE, et al. 2023.. Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination. . Nat. Commun. 14::6815
     [Crossref] [Google Scholar]
  67. 67.
    Tang J, Zeng C, Cox TM, Li C, Son YM, et al. 2022.. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. . Sci. Immunol. 7::eadd4853
     [Crossref] [Google Scholar]
  68. 68.
    Wrammert J, Onlamoon N, Akondy RS, Perng GC, Polsrila K, et al. 2012.. Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. . J. Virol. 86::2911–18
     [Crossref] [Google Scholar]
  69. 69.
    Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, et al. 2011.. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. . J. Exp. Med. 208::181–93
     [Crossref] [Google Scholar]
  70. 70.
    Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, et al. 2021.. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. . Nature 595::421–25
     [Crossref] [Google Scholar]
  71. 71.
    De Biasi S, Lo Tartaro D, Meschiari M, Gibellini L, Bellinazzi C, et al. 2020.. Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia. . Eur. J. Immunol. 50::1283–94
     [Crossref] [Google Scholar]
  72. 72.
    Nielsen SCA, Yang F, Jackson KJL, Hoh RA, Röltgen K, et al. 2020.. Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2. . Cell Host Microbe 28::516–25.e5
     [Crossref] [Google Scholar]
  73. 73.
    Halliley JL, Tipton CM, Liesveld J, Rosenberg AF, Darce J, et al. 2015.. Long-lived plasma cells are contained within the CD19−CD38hiCD138+ subset in human bone marrow. . Immunity 43::132–45
     [Crossref] [Google Scholar]
  74. 74.
    Manz RA, Thiel A, Radbruch A. 1997.. Lifetime of plasma cells in the bone marrow. . Nature 388::133–34
     [Crossref] [Google Scholar]
  75. 75.
    Slifka MK, Antia R, Whitmire JK, Ahmed R. 1998.. Humoral immunity due to long-lived plasma cells. . Immunity 8::363–72
     [Crossref] [Google Scholar]
  76. 76.
    Kim W, Zhou JQ, Horvath SC, Schmitz AJ, Sturtz AJ, et al. 2022.. Germinal centre-driven maturation of B cell response to mRNA vaccination. . Nature 604::141–45
     [Crossref] [Google Scholar]
  77. 77.
    Nayak K, Gottimukkala K, Kumar S, Reddy ES, Edara VV, et al. 2021.. Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India. . Virology 558::13–21
     [Crossref] [Google Scholar]
  78. 78.
    Matz HC, McIntire KM, Ellebedy AH. 2023.. ‘ Persistent germinal center responses: slow-growing trees bear the best fruits. .’ Curr. Opin. Immunol. 83::102332
     [Crossref] [Google Scholar]
  79. 79.
    Turner JS, O'Halloran JA, Kalaidina E, Kim W, Schmitz AJ, et al. 2021.. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. . Nature 596::109–13
     [Crossref] [Google Scholar]
  80. 80.
    Lapuente D, Winkler TH, Tenbusch M. 2024.. B-cell and antibody responses to SARS-CoV-2: infection, vaccination, and hybrid immunity. . Cell. Mol. Immunol. 21::144–58
     [Crossref] [Google Scholar]
  81. 81.
    Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman LS, et al. 2022.. Protection and waning of natural and hybrid immunity to SARS-CoV-2. . N. Engl. J. Med. 386::2201–12
     [Crossref] [Google Scholar]
  82. 82.
    Bellusci L, Grubbs G, Zahra FT, Forgacs D, Golding H, et al. 2022.. Antibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination. . Nat. Commun. 13::4617
     [Crossref] [Google Scholar]
  83. 83.
    Muik A, Lui BG, Bacher M, Wallisch A-K, Toker A, et al. 2022.. Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5. . Sci. Immunol. 7::eade2283
     [Crossref] [Google Scholar]
  84. 84.
    Quandt J, Muik A, Salisch N, Lui BG, Lutz S, et al. 2022.. Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes. . Sci. Immunol. 7::eabq2427
     [Crossref] [Google Scholar]
  85. 85.
    Park Y-J, Pinto D, Walls AC, Liu Z, De Marco A, et al. 2022.. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages. . Science 378::619–27
     [Crossref] [Google Scholar]
  86. 86.
    Wratil PR, Stern M, Priller A, Willmann A, Almanzar G, et al. 2022.. Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. . Nat. Med. 28::496–503
     [Crossref] [Google Scholar]
  87. 87.
    Kaku CI, Bergeron AJ, Ahlm C, Normark J, Sakharkar M, et al. 2022.. Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection. . Sci. Immunol. 7::eabq3511
     [Crossref] [Google Scholar]
  88. 88.
    Alsoussi WB, Malladi SK, Zhou JQ, Liu Z, Ying B, et al. 2023.. SARS-CoV-2 Omicron boosting induces de novo B cell response in humans. . Nature 617::592–98
     [Crossref] [Google Scholar]
  89. 89.
    Yisimayi A, Song W, Wang J, Jian F, Yu Y, et al. 2024.. Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting. . Nature 625::148–56
     [Crossref] [Google Scholar]
  90. 90.
    Braun J, Loyal L, Frentsch M, Wendisch D, Georg P, et al. 2020.. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. . Nature 587::270–74
     [Crossref] [Google Scholar]
  91. 91.
    Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, et al. 2020.. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. . Cell 181::1489–501.e15
     [Crossref] [Google Scholar]
  92. 92.
    Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin JB, et al. 2020.. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. . Cell 183::158–68.e14
     [Crossref] [Google Scholar]
  93. 93.
    Weiskopf D, Schmitz KS, Raadsen MP, Grifoni A, Okba NMA, et al. 2020.. Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. . Sci. Immunol. 5::eabd2071
     [Crossref] [Google Scholar]
  94. 94.
    Lakshmanappa YS, Elizaldi SR, Roh JW, Schmidt BA, Carroll TD, et al. 2021.. SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques. . Nat. Commun. 12::541
     [Crossref] [Google Scholar]
  95. 95.
    Fears AC, Walker EM, Chirichella N, Slisarenko N, Merino KM, et al. 2022.. The dynamics of γδ T cell responses in nonhuman primates during SARS-CoV-2 infection. . Commun. Biol. 5::1380
     [Crossref] [Google Scholar]
  96. 96.
    Nelson CE, Foreman TW, Fukutani ER, Kauffman KD, Sakai S, et al. 2024.. IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques. . PLOS Pathog. 20::e1012339
     [Crossref] [Google Scholar]
  97. 97.
    Liu J, Yu J, McMahan K, Jacob-Dolan C, He X, et al. 2022.. CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques. . Sci. Immunol. 7::eabq7647
     [Crossref] [Google Scholar]
  98. 98.
    Goldblatt D, Alter G, Crotty S, Plotkin SA. 2022.. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. . Immunol. Rev. 310::6–26
     [Crossref] [Google Scholar]
  99. 99.
    Kar M, Johnson KEE, Vanderheiden A, Elrod EJ, Floyd K, et al. 2024.. CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment. . Sci. Adv. 10::eadp2636
     [Crossref] [Google Scholar]
  100. 100.
    Eser TM, Baranov O, Huth M, Ahmed MIM, Deák F, et al. 2023.. Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion. . Nat. Commun. 14::2952
     [Crossref] [Google Scholar]
  101. 101.
    Yoshida M, Worlock KB, Huang N, Lindeboom RGH, Butler CR, et al. 2022.. Local and systemic responses to SARS-CoV-2 infection in children and adults. . Nature 602::321–27
     [Crossref] [Google Scholar]
  102. 102.
    Ziegler CGK, Miao VN, Owings AH, Navia AW, Tang Y, et al. 2021.. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. . Cell 184::4713–33.e22
     [Crossref] [Google Scholar]
  103. 103.
    Rodda LB, Morawski PA, Pruner KB, Fahning ML, Howard CA, et al. 2022.. Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity. . Cell 185::1588–601.e14
     [Crossref] [Google Scholar]
  104. 104.
    Dykema AG, Zhang B, Woldemeskel BA, Garliss CC, Rashid R, et al. 2022.. SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection. . eBioMedicine 80::104048
     [Crossref] [Google Scholar]
  105. 105.
    Ford ES, Mayer-Blackwell K, Jing L, Laing KJ, Sholukh AM, et al. 2024.. Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19. . Nat. Immunol. 25::166–77
     [Crossref] [Google Scholar]
  106. 106.
    Gagne M, Flynn BJ, Andrew SF, Marquez J, Flebbe DR, et al. 2024.. Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates. . Nat. Immunol. 25::1913–27
     [Crossref] [Google Scholar]
  107. 107.
    McMahan K, Wegmann F, Aid M, Sciacca M, Liu J, et al. 2024.. Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques. . Nature 626::385–91
     [Crossref] [Google Scholar]
  108. 108.
    Smith EC, Case JB, Blanc H, Isakov O, Shomron N, et al. 2015.. Mutations in coronavirus nonstructural protein 10 decrease virus replication fidelity. . J. Virol. 89::6418–26
     [Crossref] [Google Scholar]
  109. 109.
    Eckerle LD, Becker MM, Halpin RA, Li K, Venter E, et al. 2010.. Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. . PLOS Pathog. 6::e1000896
     [Crossref] [Google Scholar]
  110. 110.
    Eckerle LD, Lu X, Sperry SM, Choi L, Denison MR. 2007.. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. . J. Virol. 81::12135–44
     [Crossref] [Google Scholar]
  111. 111.
    Edridge AWD, Kaczorowska J, Hoste ACR, Bakker M, Klein M, et al. 2020.. Seasonal coronavirus protective immunity is short-lasting. . Nat. Med. 26::1691–93
     [Crossref] [Google Scholar]
  112. 112.
    Eguia RT, Crawford KHD, Stevens-Ayers T, Kelnhofer-Millevolte L, Greninger AL, et al. 2021.. A human coronavirus evolves antigenically to escape antibody immunity. . PLOS Pathog. 17::e1009453
     [Crossref] [Google Scholar]
  113. 113.
    Yewdell JW. 2021.. Antigenic drift: understanding COVID-19. . Immunity 54::2681–87
     [Crossref] [Google Scholar]
  114. 114.
    Garushyants SK, Rogozin IB, Koonin EV. 2021.. Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring. . Commun. Biol. 4::1343
     [Crossref] [Google Scholar]
  115. 115.
    Candido DS, Claro IM, de Jesus JG, Souza WM, Moreira FRR, et al. 2020.. Evolution and epidemic spread of SARS-CoV-2 in Brazil. . Science 369::1255–60
     [Crossref] [Google Scholar]
  116. 116.
    Day T, Gandon S, Lion S, Otto SP. 2020.. On the evolutionary epidemiology of SARS-CoV-2. . Curr. Biol. 30::R849–57
     [Crossref] [Google Scholar]
  117. 117.
    Pereson MJ, Mojsiejczuk L, Martínez AP, Flichman DM, Garcia GH, Di Lello FA. 2021.. Phylogenetic analysis of SARS-CoV-2 in the first few months since its emergence. . J. Med. Virol. 93::1722–31
     [Crossref] [Google Scholar]
  118. 118.
    Tao K, Tzou PL, Nouhin J, Gupta RK, de Oliveira T, et al. 2021.. The biological and clinical significance of emerging SARS-CoV-2 variants. . Nat. Rev. Genet. 22::757–73
     [Crossref] [Google Scholar]
  119. 119.
    Tegally H, Wilkinson E, Lessells RJ, Giandhari J, Pillay S, et al. 2021.. Sixteen novel lineages of SARS-CoV-2 in South Africa. . Nat. Med. 27::440–46
     [Crossref] [Google Scholar]
  120. 120.
    Pereson MJ, Flichman DM, Martínez AP, Baré P, Garcia GH, Di Lello FA. 2021.. Evolutionary analysis of SARS-CoV-2 spike protein for its different clades. . J. Med. Virol. 93::3000–6
     [Crossref] [Google Scholar]
  121. 121.
    Wang S, Xu X, Wei C, Li S, Zhao J, et al. 2022.. Molecular evolutionary characteristics of SARS-CoV-2 emerging in the United States. . J. Med. Virol. 94::310–17
     [Crossref] [Google Scholar]
  122. 122.
    Kim JI, Lee I, Park S, Bae J-Y, Yoo K, et al. 2017.. Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A (H3N2) strains in Korea. . PLOS ONE 12::e0172059
     [Crossref] [Google Scholar]
  123. 123.
    Ogando NS, Zevenhoven-Dobbe JC, van der Meer Y, Bredenbeek PJ, Posthuma CC, Snijder EJ. 2020.. The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2. . J. Virol. 94::e01246-20
     [Crossref] [Google Scholar]
  124. 124.
    Yin X, Popa H, Stapon A, Bouda E, Garcia-Diaz M. 2023.. Fidelity of ribonucleotide incorporation by the SARS-CoV-2 replication complex. . J. Mol. Biol. 435::167973
     [Crossref] [Google Scholar]
  125. 125.
    Lauring AS, Andino R. 2010.. Quasispecies theory and the behavior of RNA viruses. . PLOS Pathog. 6::e1001005
     [Crossref] [Google Scholar]
  126. 126.
    Dangerfield TL, Huang NZ, Johnson KA. 2020.. Remdesivir is effective in combating COVID-19 because it is a better substrate than ATP for the viral RNA-dependent RNA polymerase. . iScience 23::101849
     [Crossref] [Google Scholar]
  127. 127.
    Seifert M, Bera SC, van Nies P, Kirchdoerfer RN, Shannon A, et al. 2021.. Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective. . eLife 10::e70968
     [Crossref] [Google Scholar]
  128. 128.
    Shannon A, Selisko B, Le N-T-T, Huchting J, Touret F, et al. 2020.. Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis. . Nat. Commun. 11::4682
     [Crossref] [Google Scholar]
  129. 129.
    Müller NF, Kistler KE, Bedford T. 2022.. A Bayesian approach to infer recombination patterns in coronaviruses. . Nat. Commun. 13::4186
     [Crossref] [Google Scholar]
  130. 130.
    Gribble J, Stevens LJ, Agostini ML, Anderson-Daniels J, Chappell JD, et al. 2021.. The coronavirus proofreading exoribonuclease mediates extensive viral recombination. . PLOS Pathog. 17::e1009226
     [Crossref] [Google Scholar]
  131. 131.
    Li X, Giorgi EE, Marichannegowda MH, Foley B, Xiao C, et al. 2020.. Emergence of SARS-CoV-2 through recombination and strong purifying selection. . Sci. Adv. 6::eabb9153
     [Crossref] [Google Scholar]
  132. 132.
    Makarenkov V, Mazoure B, Rabusseau G, Legendre P. 2021.. Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin. . BMC Ecol. Evol. 21::5
     [Crossref] [Google Scholar]
  133. 133.
    Boni MF, Lemey P, Jiang X, Lam TT-Y, Perry BW, et al. 2020.. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. . Nat. Microbiol. 5::1408–17
     [Crossref] [Google Scholar]
  134. 134.
    Lytras S, Hughes J, Martin D, Swanepoel P, de Klerk A, et al. 2022.. Exploring the natural origins of SARS-CoV-2 in the light of recombination. . Genome Biol. Evol. 14::evac018
     [Crossref] [Google Scholar]
  135. 135.
    Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, et al. 2022.. Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. . Nature 604::330–36
     [Crossref] [Google Scholar]
  136. 136.
    Miller J, Hachmann NP, Collier A-Y, Lasrado N, Mazurek CR, et al. 2023.. Substantial neutralization escape by SARS-CoV-2 omicron variants BQ.1.1 and XBB.1. . N. Engl. J. Med. 388::662–64
     [Crossref] [Google Scholar]
  137. 137.
    Wang Q, Iketani S, Li Z, Liu L, Guo Y, et al. 2023.. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. . Cell 186::279–86.e8
     [Crossref] [Google Scholar]
  138. 138.
    Carabelli AM, Peacock TP, Thorne LG, Harvey WT, Hughes J, et al. 2023.. SARS-CoV-2 variant biology: immune escape, transmission and fitness. . Nat. Rev. Microbiol. 21::162–77
     [Google Scholar]
  139. 139.
    Planas D, Staropoli I, Michel V, Lemoine F, Donati F, et al. 2024.. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion. . Nat. Commun. 15::2254
     [Crossref] [Google Scholar]
  140. 140.
    Ma W, Fu H, Jian F, Cao Y, Li M. 2023.. Immune evasion and ACE2 binding affinity contribute to SARS-CoV-2 evolution. . Nat. Ecol. Evol. 7::1457–66
     [Crossref] [Google Scholar]
  141. 141.
    Richard M, Knauf S, Lawrence P, Mather AE, Munster VJ, et al. 2017.. Factors determining human-to-human transmissibility of zoonotic pathogens via contact. . Curr. Opin. Virol. 22::7–12
     [Crossref] [Google Scholar]
  142. 142.
    Delamater PL, Street EJ, Leslie TF, Yang YT, Jacobsen KH. 2019.. Complexity of the basic reproduction number (R0). . Emerg. Infect. Dis. 25::1–4
     [Crossref] [Google Scholar]
  143. 143.
    Volz E. 2023.. Fitness, growth and transmissibility of SARS-CoV-2 genetic variants. . Nat. Rev. Genet. 24::724–34
     [Crossref] [Google Scholar]
  144. 144.
    Manathunga SS, Abeyagunawardena IA, Dharmaratne SD. 2023.. A comparison of transmissibility of SARS-CoV-2 variants of concern. . Virol. J. 20::59
     [Crossref] [Google Scholar]
  145. 145.
    Perez-Guzman PN, Knock E, Imai N, Rawson T, Elmaci Y, et al. 2023.. Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England. . Nat. Commun. 14::4279
     [Crossref] [Google Scholar]
  146. 146.
    MacLean OA, Orton RJ, Singer JB, Robertson DL. 2020.. No evidence for distinct types in the evolution of SARS-CoV-2. . Virus Evol. 6::veaa034
     [Crossref] [Google Scholar]
  147. 147.
    MacLean OA, Lytras S, Weaver S, Singer JB, Boni MF, et al. 2021.. Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen. . PLOS Biol. 19::e3001115
     [Crossref] [Google Scholar]
  148. 148.
    Plante JA, Liu Y, Liu J, Xia H, Johnson BA, et al. 2021.. Spike mutation D614G alters SARS-CoV-2 fitness. . Nature 592::116–21
     [Crossref] [Google Scholar]
  149. 149.
    Ozono S, Zhang Y, Ode H, Sano K, Tan TS, et al. 2021.. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. . Nat. Commun. 12::848
     [Crossref] [Google Scholar]
  150. 150.
    Zhou B, Thao TTN, Hoffmann D, Taddeo A, Ebert N, et al. 2021.. SARS-CoV-2 spike D614G change enhances replication and transmission. . Nature 592::122–27
     [Crossref] [Google Scholar]
  151. 151.
    Zhang L, Jackson CB, Mou H, Ojha A, Peng H, et al. 2020.. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. . Nat. Commun. 11::6013
     [Crossref] [Google Scholar]
  152. 152.
    Liu Y, Liu J, Plante KS, Plante JA, Xie X, et al. 2022.. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. . Nature 602::294–99
     [Crossref] [Google Scholar]
  153. 153.
    Burki TK. 2021.. Lifting of COVID-19 restrictions in the UK and the Delta variant. . Lancet Respir. Med. 9::e85
     [Crossref] [Google Scholar]
  154. 154.
    Mlcochova P, Kemp SA, Dhar MS, Papa G, Meng B, et al. 2021.. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. . Nature 599::114–19
     [Crossref] [Google Scholar]
  155. 155.
    Bolze A, Luo S, White S, Cirulli ET, Wyman D, et al. 2022.. SARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads. . Cell Rep. Med. 3::100564
     [Crossref] [Google Scholar]
  156. 156.
    Campbell F, Archer B, Laurenson-Schafer H, Jinnai Y, Konings F, et al. 2021.. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021. . Euro Surveill. 26::2100509
     [Crossref] [Google Scholar]
  157. 157.
    Sheikh A, McMenamin J, Taylor B, Robertson C. 2021.. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. . Lancet 397::2461–62
     [Crossref] [Google Scholar]
  158. 158.
    Wang Y, Liu C, Zhang C, Wang Y, Hong Q, et al. 2022.. Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies. . Nat. Commun. 13::871
     [Crossref] [Google Scholar]
  159. 159.
    Liu C, Ginn HM, Dejnirattisai W, Supasa P, Wang B, et al. 2021.. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. . Cell 184::4220–36.e13
     [Crossref] [Google Scholar]
  160. 160.
    Liu Y, Rocklöv J. 2022.. The effective reproductive number of the Omicron variant of SARS-CoV-2 is several times relative to Delta. . J. Travel Med. 29::taac037
     [Crossref] [Google Scholar]
  161. 161.
    Addetia A, Piccoli L, Case JB, Park Y-J, Beltramello M, et al. 2023.. Neutralization, effector function and immune imprinting of Omicron variants. . Nature 621::592–601
     [Crossref] [Google Scholar]
  162. 162.
    Li L, Liao H, Meng Y, Li W, Han P, et al. 2022.. Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1. . Cell 185::2952–60.e10
     [Crossref] [Google Scholar]
  163. 163.
    Yue C, Song W, Wang L, Jian F, Chen X, et al. 2023.. ACE2 binding and antibody evasion in enhanced transmissibility of XBB.1.5. . Lancet Infect. Dis. 23::278–80
     [Crossref] [Google Scholar]
  164. 164.
    Yang S, Yu Y, Xu Y, Jian F, Song W, et al. 2024.. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. . Lancet Infect. Dis. 24::e70–72
     [Crossref] [Google Scholar]
  165. 165.
    Johnson BA, Xie X, Bailey AL, Kalveram B, Lokugamage KG, et al. 2021.. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. . Nature 591::293–99
     [Crossref] [Google Scholar]
  166. 166.
    Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R, et al. 2021.. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. . Nat. Microbiol. 6::899–909
     [Crossref] [Google Scholar]
  167. 167.
    Peacock TP, Sheppard CM, Brown JC, Goonawardane N, Zhou J, et al. 2021.. The SARS-CoV-2 variants associated with infections in India, B.1.617, show enhanced spike cleavage by furin. . bioRxiv 446163. https://doi.org/10.1101/2021.05.28.446163
  168. 168.
    Wrobel AG, Benton DJ, Roustan C, Borg A, Hussain S, et al. 2022.. Evolution of the SARS-CoV-2 spike protein in the human host. . Nat. Commun. 13::1178
     [Crossref] [Google Scholar]
  169. 169.
    Willett BJ, Grove J, MacLean OA, Wilkie C, De Lorenzo G, et al. 2022.. SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway. . Nat. Microbiol. 7::1161–79
     [Crossref] [Google Scholar]
  170. 170.
    McNeill VF. 2022.. Airborne transmission of SARS-CoV-2: evidence and implications for engineering controls. . Annu. Rev. Chem. Biomol. Eng. 13::123–40
     [Crossref] [Google Scholar]
  171. 171.
    Richard M, van den Brand JMA, Bestebroer TM, Lexmond P, de Meulder D, et al. 2020.. Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets. . Nat. Commun. 11::766
     [Crossref] [Google Scholar]
  172. 172.
    Hui KPY, Ng K-C, Ho JCW, Yeung H-W, Ching RHH, et al. 2022.. Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract. . eBioMedicine 83::104232
     [Crossref] [Google Scholar]
  173. 173.
    Hui KPY, Ho JCW, Cheung M-C, Ng K-C, Ching RHH, et al. 2022.. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. . Nature 603::715–20
     [Crossref] [Google Scholar]
  174. 174.
    Lamers MM, Mykytyn AZ, Breugem TI, Groen N, Knoops K, et al. 2022.. SARS-CoV-2 Omicron efficiently infects human airway, but not alveolar epithelium. . bioRxiv 476898. https://doi.org/10.1101/2022.01.19.476898
  175. 175.
    Tan KS, Ong SWX, Koh MH, Tay DJW, Aw DZH, et al. 2023.. SARS-CoV-2 Omicron variant shedding during respiratory activities. . Int. J. Infect. Dis. 131::19–25
     [Crossref] [Google Scholar]
  176. 176.
    Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, et al. 2004.. Mapping the antigenic and genetic evolution of influenza virus. . Science 305::371–76
     [Crossref] [Google Scholar]
  177. 177.
    Dörner T, Radbruch A. 2007.. Antibodies and B cell memory in viral immunity. . Immunity 27::384–92
     [Crossref] [Google Scholar]
  178. 178.
    Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, et al. 2021.. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. . N. Engl. J. Med. 384::403–16
     [Crossref] [Google Scholar]
  179. 179.
    Cevik M, Grubaugh ND, Iwasaki A, Openshaw P. 2021.. COVID-19 vaccines: keeping pace with SARS-CoV-2 variants. . Cell 184::5077–81
     [Crossref] [Google Scholar]
  180. 180.
    Nasreen S, Chung H, He S, Brown KA, Gubbay JB, et al. 2022.. Effectiveness of COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario. . Nat. Microbiol. 7::379–85
     [Crossref] [Google Scholar]
  181. 181.
    Feng S, Phillips DJ, White T, Sayal H, Aley PK, et al. 2021.. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. . Nat. Med. 27::2032–40
     [Crossref] [Google Scholar]
  182. 182.
    Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, et al. 2021.. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. . Nat. Med. 27::1205–11
     [Crossref] [Google Scholar]
  183. 183.
    Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, et al. 2021.. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. . Nature 596::276–80
     [Crossref] [Google Scholar]
  184. 184.
    Garcia-Beltran WF, Lam EC, St. Denis K, Nitido AD, Garcia ZH, et al. 2021.. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. . Cell 184::2372–83.e9. Erratum . 2021.. Cell 184: 2523
    [Google Scholar]
  185. 185.
    Greaney AJ, Loes AN, Crawford KHD, Starr TN, Malone KD, et al. 2021.. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. . Cell Host Microbe 29::463–76.e6
     [Crossref] [Google Scholar]
  186. 186.
    Greaney AJ, Starr TN, Barnes CO, Weisblum Y, Schmidt F, et al. 2021.. Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies. . Nat. Commun. 12::4196
     [Crossref] [Google Scholar]
  187. 187.
    Jangra S, Ye C, Rathnasinghe R, Stadlbauer D, Personalized Virology Initiative study group , et al. 2021.. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. . Lancet Microbe. 2::e283–84
     [Crossref] [Google Scholar]
  188. 188.
    Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, et al. 2020.. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. . Science 369::1014–18
     [Crossref] [Google Scholar]
  189. 189.
    Liu Z, VanBlargan LA, Bloyet L-M, Rothlauf PW, Chen RE, et al. 2021.. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. . Cell Host Microbe 29::477–88
     [Crossref] [Google Scholar]
  190. 190.
    McCallum M, Bassi J, De Marco A, Chen A, Walls AC, et al. 2021.. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. . Science 373::648–54
     [Crossref] [Google Scholar]
  191. 191.
    Barnes CO, Jette CA, Abernathy ME, Dam KA, Esswein SR, et al. 2020.. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. . Nature 588::682–87
     [Crossref] [Google Scholar]
  192. 192.
    Chen RE, Zhang X, Case JB, Winkler ES, Liu Y, et al. 2021.. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. . Nat. Med. 27::717–26
     [Crossref] [Google Scholar]
  193. 193.
    Starr TN, Greaney AJ, Addetia A, Hannon WW, Choudhary MC, et al. 2021.. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. . Science 371::850–54
     [Crossref] [Google Scholar]
  194. 194.
    Wang P, Nair MS, Liu L, Iketani S, Luo Y, et al. 2021.. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. . Nature 593::130–35
     [Crossref] [Google Scholar]
  195. 195.
    Motozono C, Toyoda M, Zahradnik J, Saito A, Nasser H, et al. 2021.. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. . Cell Host Microbe 29::1124–36.e11
     [Crossref] [Google Scholar]
  196. 196.
    Viana R, Moyo S, Amoako DG, Tegally H, Scheepers C, et al. 2022.. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. . Nature 603::679–86
     [Crossref] [Google Scholar]
  197. 197.
    Dejnirattisai W, Huo J, Zhou D, Zahradnik J, Supasa P, et al. 2022.. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. . Cell 185::467–84.e15
     [Crossref] [Google Scholar]
  198. 198.
    McCallum M, Czudnochowski N, Rosen LE, Zepeda SK, Bowen JE, et al. 2022.. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. . Science 375::864–68
     [Crossref] [Google Scholar]
  199. 199.
    Huang M, Wu L, Zheng A, Xie Y, He Q, et al. 2022.. Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3. . Immunity 55::1501–14.e3
     [Crossref] [Google Scholar]
  200. 200.
    VanBlargan LA, Errico JM, Halfmann PJ, Zost SJ, Crowe JE Jr., et al. 2022.. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. . Nat Med 28::490–95
     [Crossref] [Google Scholar]
  201. 201.
    Pulliam JRC, van Schalkwyk C, Govender N, von Gottberg A, Cohen C, et al. 2022.. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa. . Science 376::eabn4947
     [Crossref] [Google Scholar]
  202. 202.
    Cele S, Jackson L, Khoury DS, Khan K, Moyo-Gwete T, et al. 2022.. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. . Nature 602::654–56
     [Crossref] [Google Scholar]
  203. 203.
    Khan K, Karim F, Ganga Y, Bernstein M, Jule Z, et al. 2022.. Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection. . Nat. Commun. 13::4686
     [Crossref] [Google Scholar]
  204. 204.
    Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, Zhou D, Ginn HM, et al. 2022.. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. . Cell 185::2422–33.e13
     [Crossref] [Google Scholar]
  205. 205.
    Zhou J, Sukhova K, Peacock TP, McKay PF, Brown JC, et al. 2023.. Omicron breakthrough infections in vaccinated or previously infected hamsters. . PNAS 120::e2308655120
     [Crossref] [Google Scholar]
  206. 206.
    Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, et al. 2022.. Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant. . N. Engl. J. Med. 386::1532–46
     [Crossref] [Google Scholar]
  207. 207.
    Tseng HF, Ackerson BK, Luo Y, Sy LS, Talarico CA, et al. 2022.. Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants. . Nat. Med. 28::1063–71
     [Crossref] [Google Scholar]
  208. 208.
    Firouzabadi N, Ghasemiyeh P, Moradishooli F, Mohammadi-Samani S. 2023.. Update on the effectiveness of COVID-19 vaccines on different variants of SARS-CoV-2. . Int. Immunopharmacol. 117::109968
     [Crossref] [Google Scholar]
  209. 209.
    Bowen JE, Addetia A, Dang HV, Stewart C, Brown JT, et al. 2022.. Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. . Science 377::890–94
     [Crossref] [Google Scholar]
  210. 210.
    Focosi D, Quiroga R, McConnell S, Johnson MC, Casadevall A. 2023.. Convergent evolution in SARS-CoV-2 spike creates a variant soup from which new COVID-19 waves emerge. . Int. J. Mol. Sci. 24::2264
     [Crossref] [Google Scholar]
  211. 211.
    Dijokaite-Guraliuc A, Das R, Zhou D, Ginn HM, Liu C, et al. 2023.. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses. . Cell Rep. 42::112271
     [Crossref] [Google Scholar]
  212. 212.
    Gruell H, Vanshylla K, Korenkov M, Tober-Lau P, Zehner M, et al. 2022.. SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns. . Cell Host Microbe 30::1231–41.e6
     [Crossref] [Google Scholar]
  213. 213.
    Wang Q, Guo Y, Iketani S, Nair MS, Li Z, et al. 2022.. Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5. . Nature 608::603–8
     [Crossref] [Google Scholar]
  214. 214.
    Muik A, Lui BG, Wallisch A-K, Bacher M, Mühl J, et al. 2022.. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera. . Science 375::678–80
     [Crossref] [Google Scholar]
  215. 215.
    Tseng HF, Ackerson BK, Bruxvoort KJ, Sy LS, Tubert JE, et al. 2023.. Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. . Nat. Commun. 14::189
     [Crossref] [Google Scholar]
  216. 216.
    Kurhade C, Zou J, Xia H, Cai H, Yang Q, et al. 2022.. Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine. . Nat. Commun. 13::3602
     [Crossref] [Google Scholar]
  217. 217.
    Plumb ID, Briggs Hagen M, Wiegand R, Dumyati G, Myers C, et al. 2024.. Effectiveness of a bivalent mRNA vaccine dose against symptomatic SARS-CoV-2 infection among U.S. Healthcare personnel, September 2022–May 2023. . Vaccine 42::2543–52
     [Crossref] [Google Scholar]
  218. 218.
    Kurhade C, Zou J, Xia H, Liu M, Chang HC, et al. 2023.. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster. . Nat. Med. 29::344–47
     [Crossref] [Google Scholar]
  219. 219.
    Cao Y, Song W, Wang L, Liu P, Yue C, et al. 2022.. Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75. . Cell Host Microbe 30::1527–39.e5
     [Crossref] [Google Scholar]
  220. 220.
    He Q, Wu L, Xu Z, Wang X, Xie Y, et al. 2023.. An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB. . Cell Rep. Med. 4::100991
     [Crossref] [Google Scholar]
  221. 221.
    Uriu K, Ito J, Kosugi Y, Tanaka YL, Mugita Y, et al. 2023.. Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant. . Lancet Infect. Dis. 23::e460–61
     [Crossref] [Google Scholar]
  222. 222.
    Khan K, Lustig G, Römer C, Reedoy K, Jule Z, et al. 2023.. Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant. . Nat. Commun. 14::8078
     [Crossref] [Google Scholar]
  223. 223.
    Tas JMJ, Koo J-H, Lin Y-C, Xie Z, Steichen JM, et al. 2022.. Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses. . Immunity 55::1856–71.e6
     [Crossref] [Google Scholar]
  224. 224.
    Schiepers A, van't Wout MFL, Hobbs A, Mesin L, Victora GD. 2024.. Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers. . Immunity 57::1618–28.E4
     [Crossref] [Google Scholar]
  225. 225.
    Liang C-Y, Raji S, Liu Z, Li Y, Arunkumar GAA, et al. 2024.. Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines. . Nature 630::950–60
     [Crossref] [Google Scholar]
  226. 226.
    Tortorici MA, Addetia A, Seo AJ, Brown J, Sprouse K, et al. 2024.. Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans. . Immunity 57::904–11.e4
     [Crossref] [Google Scholar]
  227. 227.
    Huiberts AJ, Hoeve CE, de Gier B, Cremer J, van der Veer B, et al. 2024.. Effectiveness of Omicron XBB.1.5 vaccine against infection with SARS-CoV-2 Omicron XBB and JN.1 variants, prospective cohort study, the Netherlands, October 2023 to January 2024. . Euro Surveill. 29::2400109
     [Crossref] [Google Scholar]
  228. 228.
    Link-Gelles R, Ciesla AA, Mak J, Miller JD, Silk BJ, et al. 2024.. Early estimates of updated 2023–2024 (monovalent XBB.1.5) COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection attributable to co-circulating Omicron variants among immunocompetent adults—increasing community access to testing program, United States, September 2023–January 2024. . MMWR Morb. Mortal. Wkly. Rep. 73::77–83
     [Crossref] [Google Scholar]
  229. 229.
    Link-Gelles R, Ciesla AA, Fleming-Dutra KE, Smith ZR, Britton A, et al. 2022.. Effectiveness of bivalent mRNA vaccines in preventing symptomatic SARS-CoV-2 infection—increasing community access to testing program, United States, September–November 2022. . MMWR Morb. Mortal. Wkly. Rep. 71::1526–30
     [Crossref] [Google Scholar]
  230. 230.
    Huiberts AJ, de Gier B, Hoeve CE, de Melker HE, Hahné SJM, et al. 2023.. Effectiveness of bivalent mRNA booster vaccination against SARS-CoV-2 Omicron infection, the Netherlands, September to December 2022. . Euro Surveill. 28::2300087
     [Crossref] [Google Scholar]
  231. 231.
    Wang Q, Guo Y, Bowen A, Mellis IA, Valdez R, et al. 2024.. XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1. . Cell Host Microbe 32::315–21.e3
     [Crossref] [Google Scholar]
  232. 232.
    Moss P. 2022.. The T cell immune response against SARS-CoV-2. . Nat. Immunol. 23::186–93
     [Crossref] [Google Scholar]
  233. 233.
    Sette A, Sidney J, Crotty S. 2023.. T cell responses to SARS-CoV-2. . Annu. Rev. Immunol. 41::343–73
     [Crossref] [Google Scholar]
  234. 234.
    Dolton G, Rius C, Hasan MS, Wall A, Szomolay B, et al. 2022.. Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. . Cell 185::2936–51.e19
     [Crossref] [Google Scholar]
  235. 235.
    de Silva TI, Liu G, Lindsey BB, Dong D, Moore SC, et al. 2021.. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. . iScience 24::103353
     [Crossref] [Google Scholar]
  236. 236.
    Reynolds CJ, Pade C, Gibbons JM, Butler DK, Otter AD, et al. 2021.. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose. . Science 372::1418–23
     [Crossref] [Google Scholar]
  237. 237.
    Riou C, Keeton R, Moyo-Gwete T, Hermanus T, Kgagudi P, et al. 2022.. Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity. . Sci. Transl. Med. 14::eabj6824
     [Crossref] [Google Scholar]
  238. 238.
    Tarke A, Sidney J, Methot N, Yu ED, Zhang Y, et al. 2021.. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. . Cell Rep. Med. 2::100355
     [Crossref] [Google Scholar]
  239. 239.
    Redd AD, Nardin A, Kared H, Bloch EM, Abel B, et al. 2022.. Minimal crossover between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T-cell epitopes identified in COVID-19 convalescent individuals. . mBio 13::e03617-21
     [Crossref] [Google Scholar]
  240. 240.
    Naranbhai V, Nathan A, Kaseke C, Berrios C, Khatri A, et al. 2022.. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals. . Cell 185::1041–51.e6
     [Crossref] [Google Scholar]
  241. 241.
    Tarke A, Coelho CH, Zhang Z, Dan JM, Yu ED, et al. 2022.. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. . Cell 185::847–59.e11
     [Crossref] [Google Scholar]
  242. 242.
    Kim S-H, Kim J, Jung S, Noh JY, Kim J, et al. 2024.. Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants. . Sci. Immunol. 9::eade6132
     [Crossref] [Google Scholar]
  243. 243.
    Tseng HF, Ackerson BK, Sy LS, Tubert JE, Luo Y, et al. 2023.. mRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States. . Nat. Commun. 14::5851
     [Crossref] [Google Scholar]
  244. 244.
    Lin D-Y, Xu Y, Gu Y, Zeng D, Wheeler B, et al. 2023.. Effectiveness of bivalent boosters against severe Omicron infection. . N. Engl. J. Med. 388::764–66
     [Crossref] [Google Scholar]
  245. 245.
    Traut CC, Blankson JN. 2023.. Bivalent mRNA vaccine-elicited SARS-CoV-2 specific T cells recognise the omicron XBB sublineage. . Lancet Microbe 4::e388
     [Crossref] [Google Scholar]
  246. 246.
    Sohail MS, Ahmed SF, Quadeer AA, McKay MR. 2024.. Cross-reactivity assessment of vaccine-derived SARS-CoV-2 T cell responses against BA.2.86 and JN.1. . Viruses 16::473
     [Crossref] [Google Scholar]
  247. 247.
    Maher MC, Bartha I, Weaver S, di Iulio J, Ferri E, et al. 2022.. Predicting the mutational drivers of future SARS-CoV-2 variants of concern. . Sci. Transl. Med. 14::eabk3445
     [Crossref] [Google Scholar]
  248. 248.
    Obermeyer F, Jankowiak M, Barkas N, Schaffner SF, Pyle JD, et al. 2022.. Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness. . Science 376::1327–32
     [Crossref] [Google Scholar]
  249. 249.
    Barut GT, Halwe NJ, Taddeo A, Kelly JN, Schön J, et al. 2022.. The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype. . Nat. Commun. 13::5929
     [Crossref] [Google Scholar]
  250. 250.
    Pilapitiya D, Wheatley AK, Tan H-X. 2023.. Mucosal vaccines for SARS-CoV-2: triumph of hope over experience. . eBioMedicine 92::104585
     [Crossref] [Google Scholar]
  251. 251.
    Ying B, Darling TL, Desai P, Liang C-Y, Dmitriev IP, et al. 2024.. Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection. . Nat. Immunol. 25::537–51
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-immunol-083122-043054
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SARS-CoV-2: The Interplay Between Evolution and Host Immunity
Annual Review of Immunology 43, 29 (2025); https://doi.org/10.1146/annurev-immunol-083122-043054
/content/journals/10.1146/annurev-immunol-083122-043054
/content/journals/10.1146/annurev-immunol-083122-043054
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