{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:14:23Z","timestamp":1791562463133,"version":"4.3.4"},"reference-count":138,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell\u2013cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell\u2013cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell\u2013cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell\u2013cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.<\/jats:p>","DOI":"10.3390\/v17111405","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mechanisms of Cell\u2013Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-7516","authenticated-orcid":false,"given":"Kate Chander","family":"Chiang","sequence":"first","affiliation":[{"name":"University College Dublin School of Medicine, Belfield, 4 Dublin, Ireland"},{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2430-2495","authenticated-orcid":false,"given":"Cheng En Nicole","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0557-5489","authenticated-orcid":false,"given":"Mazharul","family":"Altaf","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-5574","authenticated-orcid":false,"given":"Mark Tsz Kin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK"},{"name":"Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-1808","authenticated-orcid":false,"given":"Ravindra K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK"},{"name":"Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK"},{"name":"Africa Health Research Institute, Durban KZN 031, South Africa"},{"name":"Hong Kong Jockey Club Global Health Institute, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s43856-024-00457-3","article-title":"Neutralizing antibodies after the third COVID-19 vaccination in healthcare workers with or without breakthrough infection","volume":"4","author":"Reinholm","year":"2024","journal-title":"Commun. 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