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SARS-CoV-2 variants: biology, pathogenicity, immunity and control

Nature Reviews Microbiology volume 24, pages 8–28 (2026)Cite this article

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Abstract

More than 5 years have passed since the emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet this virus continues to circulate globally, undergoing evolutionary changes. The effective control of SARS-CoV-2 necessitates an understanding of its antigenicity, replicative capacity, pathogenicity and transmissibility, as well as the development of preventive and treatment options. In this Review, we describe the origins and evolution of SARS-CoV-2, and outline variant and subvariant-specific characteristics. We also discuss the challenges faced in implementing prevention and treatment methods, such as the emergence of antigenically distinct variants and the phenomenon of immune imprinting. This Review provides insights into combating the ongoing COVID-19 pandemic and guidance for future research and vaccine development efforts.

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Fig. 1: Severe acute respiratory syndrome coronavirus 2 variant transitions between 15 February 2020 and 23 July 2025.
Fig. 2: Divergence of the spike protein sequences in major severe acute respiratory syndrome coronavirus 2 variants.
Fig. 3: The effect of variant-specific substitutions on the life cycle of severe acute respiratory syndrome coronavirus 2.
Fig. 4: Humoral immune response outcomes after exposure to viral antigens.

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Acknowledgements

We gratefully acknowledge all GISAID data contributors, that is, the authors and their originating laboratories responsible for obtaining the specimens, and their submitting laboratories for generating the genetic sequence and metadata and sharing via the GISAID Initiative, on which the information in this Review is based. The complete set of GISAID metadata available through to 23 July 2025 was used to generate Fig. 1 and Supplementary Figs. 3–5243. This included metadata associated with 17,385,806 sequences available via the EPI_SET identifier: EPI_SET_250725aw, located at https://doi.org/10.55876/gis8.250725aw. For the phylogenetic tree in Supplmentary Fig. 1, the 7,249 SARS-CoV-2 full-length genomes were used; GISAID accession numbers are available via the EPI_SET identifier EPI_SET_250726xe, located at https://doi.org/10.55876/gis8.250726xe. We thank S. Watson (Obsidia Communications LLC.) for language editing. We also thank C.-Y. Liang (Washington University School of Medicine, St Louis) for preparing Fig. 4. We thank J. Theiler and W. Fischer (Los Alamos National Laboratory) for helping with Fig. 1 and Supplementary Figs. 1, 3, 4 and 5; W. Fischer and H. Yoon (Los Alamos National Laboratory) for processing the GISAID data; and the GISAID team for supporting our studies. We also thank the Pango nomenclature team for upkeep of the naming system used here, C. Roemer for his lineage notes, and A. Hinrichs for phylogenetic confirmation of the Pango designations using Usher. The authors acknowledge the support of grants from the Japan Program for Infectious Diseases Research and Infrastructure (no. JP20wm0125002), the Japan Initiative for World-leading Vaccine Research and Development Centers (no. JP223fa627001) and the Program on R&D of new generation vaccine including new modality application (no. JP223fa827005) from the Japan Agency for Medical Research and Development (AMED). B.K. acknowledges the support of the Gates Foundation grant nos. INV-048656 and INV-042469 and NIH, NIAID, DMID grant no. P01 AI158571. M.S.D. acknowledges the support of grants and contracts from the NIH (nos. P01 AI168347, R01 AI157155, CEIRR 75N93021C00017 and 75N93021C00014).

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Authors and Affiliations

  1. The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan

    Ryuta Uraki & Yoshihiro Kawaoka

  2. Division of Virology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Ryuta Uraki & Yoshihiro Kawaoka

  3. The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (The UTOPIA Center), Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan

    Ryuta Uraki & Yoshihiro Kawaoka

  4. Theoretical Biology and Biophysics, T6, Theory Division, Los Alamos National Laboratory, Los Alamos, NM, USA

    Bette Korber

  5. The New Mexico Consortium, Los Alamos, NM, USA

    Bette Korber

  6. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA

    Michael S. Diamond

  7. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA

    Michael S. Diamond

  8. Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, USA

    Michael S. Diamond

  9. Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St Louis, MO, USA

    Michael S. Diamond

  10. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA

    Michael S. Diamond

  11. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, USA

    Yoshihiro Kawaoka

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The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Bette Korber, Michael S. Diamond or Yoshihiro Kawaoka.

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Competing interests

Y.K. has received grant support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Shionogi, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation and Fuji Rebio. Y.K. is a co-founder of FluGen. M.S.D. is a consultant or adviser for Inbios, Moderna, IntegerBio, Merck, GlaxoSmithKline and Akagera Medicines. The laboratory of M.S.D. has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology and IntegerBio. The other authors declare no competing interests.

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Nature Reviews Microbiology thanks Volker Thiel, who co-reviewed with G. Tuba Barut; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

64 vaccines have been approved: https://www.unicef.org/supply/covid-19-market-dashboard

COVID-19 cases were tracked until March 2023: https://github.com/CSSEGISandData/COVID-19

‘Embers’ tool: https://cov.lanl.gov/

Global Initiative on Sharing All Influenza Data: https://gisaid.org/

Pango lineage designations: https://github.com/cov-lineages/pango-designation/blob/master/lineage_notes.txt

WHO continues to monitor and assess variants: https://www.who.int/groups/technical-advisory-group-on-virus-evolution

WHO COVID-19 dashboard: https://covid19.who.int/

WHO nomenclature: https://www.who.int/activities/tracking-SARS-CoV-2-variants

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Uraki, R., Korber, B., Diamond, M.S. et al. SARS-CoV-2 variants: biology, pathogenicity, immunity and control. Nat Rev Microbiol 24, 8–28 (2026). https://doi.org/10.1038/s41579-025-01255-x

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