{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:10:11Z","timestamp":1790471411950,"version":"4.1.0"},"posted":{"date-parts":[[2022,7,2]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":94,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,7,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.<\/jats:p>","DOI":"10.1101\/2022.06.29.22276868","type":"posted-content","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T12:30:12Z","timestamp":1656765012000},"source":"Crossref","is-referenced-by-count":20,"title":["Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection"],"prefix":"10.64898","author":[{"given":"Chrispin","family":"Chaguza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Petrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntai","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallery I.","family":"Breban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kien","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario A.","family":"Pe\u00f1a-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Castaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verity","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Yale SARS-CoV-2 Genomic Surveillance Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-4028","authenticated-orcid":false,"given":"Wade","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald I.","family":"Swanstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan D.","family":"Grubaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2022070408250898000_2022.06.29.22276868v1.1","doi-asserted-by":"crossref","unstructured":"Aggarwal, D. , Warne, B. , Jahun, A. , Hamilton, W. , Fieldman, T. , Plessis, L. , Hill, V. , Blane, B. , Watkins, E. , Wright, E. , et al. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission. https:\/\/doi.org\/10.21203\/rs.3.rs-520627\/v1.","DOI":"10.21203\/rs.3.rs-520627\/v1"},{"key":"2022070408250898000_2022.06.29.22276868v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2119451"},{"key":"2022070408250898000_2022.06.29.22276868v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2020.10.049"},{"key":"2022070408250898000_2022.06.29.22276868v1.4","doi-asserted-by":"crossref","unstructured":"Borges, V. , Isidro, J. , Cunha, M. , Cochicho, D. , Martins, L. , Banha, L. , Figueiredo, M. , Rebelo, L. , Trindade, M.C. , Duarte, S. , et al. (2021). Long-Term Evolution of SARS-CoV-2 in an Immunocompromised Patient with Non-Hodgkin Lymphoma. mSphere 6. https:\/\/doi.org\/10.1128\/msphere.00244-21.","DOI":"10.1128\/mSphere.00244-21"},{"key":"2022070408250898000_2022.06.29.22276868v1.5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s10875-021-01158-5","article-title":"Persistent COVID-19 Infection in Wiskott-Aldrich Syndrome Cleared Following Therapeutic Vaccination: a Case Report","volume":"42","author":"Immunodeficiency Centre for Wales","year":"2022","journal-title":"J. Clin. 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(2020). Temporal signal and the phylodynamic threshold of SARS-CoV-2. Virus Evol 6, veaa061. .","DOI":"10.1093\/ve\/veaa061"},{"key":"2022070408250898000_2022.06.29.22276868v1.18","doi-asserted-by":"crossref","unstructured":"Farjo, M. , Koelle, K. , Martin, M.A. , Gibson, L.L. , Walden, K.K.O. , Rendon, G. , Fields, C.J. , Alnaji, F. , Gallagher, N. , Luo, C.H. , et al. 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Intrahost evolution and forward transmission of a novel SARS-CoV-2 Omicron BA.1 subvariant. https:\/\/doi.org\/10.1101\/2022.05.25.22275533.","DOI":"10.1101\/2022.05.25.22275533"},{"key":"2022070408250898000_2022.06.29.22276868v1.23","doi-asserted-by":"crossref","first-page":"veab091","DOI":"10.1093\/ve\/veab091","article-title":"Identification of a novel SARS-CoV-2 P.1 sub-lineage in Brazil provides new insights about the mechanisms of emergence of variants of concern","volume":"7","year":"2021","journal-title":"Virus Evol"},{"key":"2022070408250898000_2022.06.29.22276868v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/J.CHOM.2021.02.003"},{"key":"2022070408250898000_2022.06.29.22276868v1.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090727"},{"key":"2022070408250898000_2022.06.29.22276868v1.26","doi-asserted-by":"crossref","first-page":"6222","DOI":"10.1016\/j.cell.2021.11.013","article-title":"Of variants and vaccines","volume":"184","year":"2021","journal-title":"Cell"},{"key":"2022070408250898000_2022.06.29.22276868v1.27","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1618-7"},{"key":"2022070408250898000_2022.06.29.22276868v1.28"},{"key":"2022070408250898000_2022.06.29.22276868v1.29","doi-asserted-by":"crossref","unstructured":"Halfmann, P.J. , Minor, N.R. , Haddock, L.A. , Maddox, R. , Moreno, G.K. , Braun, K.M. , Baker, D.A. , Riemersa, K.K. , Prasad, A. , Alman, K.J. , et al. Evolution of a globally unique SARS-CoV- 2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual. https:\/\/doi.org\/10.1101\/2022.04.11.22272784.","DOI":"10.1101\/2022.04.11.22272784"},{"key":"2022070408250898000_2022.06.29.22276868v1.30","doi-asserted-by":"crossref","unstructured":"Harari, S. , Tahor, M. , Rutsinsky, N. , Meijer, S. , Miller, D. , Henig, O. , Halutz, O. , Levytskyi, K. , Ben-Ami, R. , Adler, A. , et al. 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Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host. https:\/\/doi.org\/10.1101\/2021.01.10.20248871.","DOI":"10.1101\/2021.01.10.20248871"},{"key":"2022070408250898000_2022.06.29.22276868v1.41","doi-asserted-by":"crossref","unstructured":"Ko, K.K.K. , Yingtaweesittikul, H. , Tan, T.T. , Wijaya, L. , Cao, D.Y. , Goh, S.S. , Abdul Rahman, N.B. , Chan, K.X.L. , Tay, H.M. , Sim, J.H.C. , et al. (2022). Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts. 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(2021). Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Host Displaying Treatment Induced Viral Evolution. Open Forum Infect Dis 8, ofab295. .","DOI":"10.1093\/ofid\/ofab295"},{"key":"2022070408250898000_2022.06.29.22276868v1.58","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1056\/NEJMp2118468","article-title":"Universal Coronavirus Vaccines \u2014 An Urgent Need","volume":"386","year":"2022","journal-title":"New England Journal of Medicine"},{"key":"2022070408250898000_2022.06.29.22276868v1.59","doi-asserted-by":"crossref","unstructured":"Nadeau, S.A. , Vaughan, T.G. , Scire, J. , Huisman, J.S. , and Stadler, T . (2021). The origin and early spread of SARS-CoV-2 in Europe. Proc. Natl. Acad. Sci. U. S. A. 118. https:\/\/doi.org\/10.1073\/pnas.2012008118.","DOI":"10.1073\/pnas.2012008118"},{"key":"2022070408250898000_2022.06.29.22276868v1.60","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/s41591-021-01378-7","article-title":"COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence","volume":"27","year":"2021","journal-title":"Nat. Med"},{"key":"2022070408250898000_2022.06.29.22276868v1.61","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu300"},{"key":"2022070408250898000_2022.06.29.22276868v1.62","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab622"},{"key":"2022070408250898000_2022.06.29.22276868v1.63","doi-asserted-by":"crossref","unstructured":"O\u2019Toole, \u00c1. , Scher, E. , Underwood, A. , Jackson, B. , Hill, V. , McCrone, J.T. , Colquhoun, R. , Ruis, C. , Abu-Dahab, K. , Taylor, B. , et al. (2021). Assignment of Epidemiological Lineages in an Emerging Pandemic Using the Pangolin Tool. 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Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2. Sci. Transl. 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Elife 10. https:\/\/doi.org\/10.7554\/eLife.66857.","DOI":"10.7554\/eLife.66857"},{"key":"2022070408250898000_2022.06.29.22276868v1.81","doi-asserted-by":"crossref","first-page":"103355","DOI":"10.1016\/j.ebiom.2021.103355","article-title":"Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: A consecutive case series","volume":"67","year":"2021","journal-title":"EBioMedicine"},{"key":"2022070408250898000_2022.06.29.22276868v1.82","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-022-04411-y","article-title":"Rapid epidemic expansion of the SARS-CoV- 2 Omicron variant in southern Africa","volume":"603","year":"2022","journal-title":"Nature"},{"key":"2022070408250898000_2022.06.29.22276868v1.83","doi-asserted-by":"crossref","unstructured":"Viberg, L.T. , Sarovich, D.S. , Kidd, T.J. , Geake, J.B. , Bell, S.C. , Currie, B.J. , and Price, E.P . (2017). 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MBio 8. https:\/\/doi.org\/10.1128\/mBio.00356-17.","DOI":"10.1128\/mBio.00356-17"},{"key":"2022070408250898000_2022.06.29.22276868v1.84","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/s41564-020-0761-6","article-title":"Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe sets","volume":"5","year":"2020","journal-title":"Nat Microbiol"},{"key":"2022070408250898000_2022.06.29.22276868v1.85","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001236"},{"key":"2022070408250898000_2022.06.29.22276868v1.86","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41586-021-03470-x","article-title":"Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England","volume":"593","year":"2021","journal-title":"Nature"},{"key":"2022070408250898000_2022.06.29.22276868v1.87","doi-asserted-by":"crossref","unstructured":"Weigang, S. , Fuchs, J. , Zimmer, G. , Schnepf, D. , Kern, L. , Beer, J. , Luxenburger, H. , Ankerhold, J. , Falcone, V. , Kemming, J. , et al. (2021). Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants. Nature Communications 12. https:\/\/doi.org\/10.1038\/s41467-021-26602-3.","DOI":"10.1038\/s41467-021-26602-3"},{"key":"2022070408250898000_2022.06.29.22276868v1.88","doi-asserted-by":"crossref","unstructured":"Weisblum, Y. , Schmidt, F. , Zhang, F. , DaSilva, J. , Poston, D. , Lorenzi, J.C. , Muecksch, F. , Rutkowska, M. , Hoffmann, H.-H. , Michailidis, E. , et al. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 9. https:\/\/doi.org\/10.7554\/eLife.61312.","DOI":"10.7554\/eLife.61312"},{"key":"2022070408250898000_2022.06.29.22276868v1.89","doi-asserted-by":"crossref","unstructured":"Wertheim, J.O. , Wang, J.C. , Leelawong, M. , Martin, D.P. , Havens, J.L. , Chowdhury, M.A. , Pekar, J. , Amin, H. , Arroyo, A. , Awandare, G.A. , et al. Capturing intrahost recombination of SARS-CoV-2 during superinfection with Alpha and Epsilon variants in New York City. https:\/\/doi.org\/10.1101\/2022.01.18.22269300.","DOI":"10.1101\/2022.01.18.22269300"},{"key":"2022070408250898000_2022.06.29.22276868v1.90","doi-asserted-by":"crossref","unstructured":"Wilkinson, S.A.J. , Richter, A. , Casey, A. , Osman, H. , Mirza, J.D. , Stockton, J. , Quick, J. , Ratcliffe, L. , Sparks, N. , Cumley, N. , et al. Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients. https:\/\/doi.org\/10.1101\/2022.03.02.22271697.","DOI":"10.1101\/2022.03.02.22271697"},{"key":"2022070408250898000_2022.06.29.22276868v1.91","doi-asserted-by":"crossref","unstructured":"Williamson, M.K. , Hamilton, F. , Hutchings, S. , Pymont, H.M. , Hackett, M. , Arnold, D. , Maskell, N.A. , MacGowan, A. , Albur, M. , Jenkins, M. , et al. Chronic SARS-CoV-2 infection and viral evolution in a hypogammaglobulinaemic individual. https:\/\/doi.org\/10.1101\/2021.05.31.21257591.","DOI":"10.1101\/2021.05.31.21257591"},{"key":"2022070408250898000_2022.06.29.22276868v1.92","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3"},{"key":"2022070408250898000_2022.06.29.22276868v1.93","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00522-15"},{"key":"2022070408250898000_2022.06.29.22276868v1.94","first-page":"e3938","article-title":"Primer ID Next-Generation Sequencing for the Analysis of a Broad Spectrum Antiviral Induced Transition Mutations and Errors Rates in a Coronavirus Genome","volume":"11","year":"2021","journal-title":"Bio Protoc"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2022.06.29.22276868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:45:58Z","timestamp":1768488358000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2022.06.29.22276868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,2]]},"references-count":94,"URL":"https:\/\/doi.org\/10.1101\/2022.06.29.22276868","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.xcrm.2023.100943","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2022,7,2]]},"subtype":"preprint"}}