Persistence of SARS‐CoV‐2 infection and viral intra‐ and inter‐host evolution in COVID‐19 hospitalized patients
Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) persistence in COVID‐19 patients could play a key role in the emergence of variants of concern. The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct...
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creator | Pavia, Grazia Quirino, Angela Marascio, Nadia Veneziano, Claudia Longhini, Federico Bruni, Andrea Garofalo, Eugenio Pantanella, Marta Manno, Michele Gigliotti, Simona Giancotti, Aida Barreca, Giorgio Settimo Branda, Francesco Torti, Carlo Rotundo, Salvatore Lionello, Rosaria La Gamba, Valentina Berardelli, Lavinia Gullì, Sara Palma Trecarichi, Enrico Maria Russo, Alessandro Palmieri, Camillo De Marco, Carmela Viglietto, Giuseppe Casu, Marco Sanna, Daria Ciccozzi, Massimo Scarpa, Fabio Matera, Giovanni |
description | Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) persistence in COVID‐19 patients could play a key role in the emergence of variants of concern. The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID‐19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID‐19 patients with persistent SARS‐CoV‐2 infection, from January 2022 to March 2023, was conducted. To characterize the intra‐ and inter‐host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS‐CoV‐2 intra‐host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host‐based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro‐active genomic surveillance of persistent SARS‐CoV‐2 infected patients is recommended to identify genetically divergent lineages before their diffusion. |
doi_str_mv | 10.1002/jmv.29708 |
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The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID‐19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID‐19 patients with persistent SARS‐CoV‐2 infection, from January 2022 to March 2023, was conducted. To characterize the intra‐ and inter‐host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS‐CoV‐2 intra‐host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host‐based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro‐active genomic surveillance of persistent SARS‐CoV‐2 infected patients is recommended to identify genetically divergent lineages before their diffusion.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.29708</identifier><identifier>PMID: 38804179</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Bayes Theorem ; Bayesian analysis ; Coronaviruses ; COVID-19 ; COVID-19 - epidemiology ; COVID-19 - transmission ; COVID-19 - virology ; Divergence ; Evolution ; Evolution, Molecular ; Female ; Gene sequencing ; Genome, Viral - genetics ; Genomic analysis ; Glycoproteins ; Hospitalization ; Humans ; Infections ; Infectivity ; inter‐host viral genetic evolution ; intra‐host viral genetic evolution ; Longitudinal Studies ; Male ; Middle Aged ; Nasopharynx - virology ; Persistent infection ; phylodynamic analysis ; phylogenetic analysis ; Phylogenetics ; Phylogeny ; Respiratory diseases ; Retrospective Studies ; SARS-CoV-2 - classification ; SARS-CoV-2 - genetics ; SARS‐CoV‐2 immune escape mutations ; SARS‐CoV‐2 persistence ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - genetics ; Statistical inference ; Viral diseases ; Whole Genome Sequencing</subject><ispartof>Journal of medical virology, 2024-06, Vol.96 (6), p.e29708-n/a</ispartof><rights>2024 Wiley Periodicals LLC.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2438-d09b527b3cea94b95900c014c4f7a382098f69969e402ed57825fc4e6c77275c3</cites><orcidid>0000-0002-3501-714X ; 0000-0001-7631-5453 ; 0000-0003-3866-9239</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.29708$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.29708$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27933,27934,45583,45584</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38804179$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavia, Grazia</creatorcontrib><creatorcontrib>Quirino, Angela</creatorcontrib><creatorcontrib>Marascio, Nadia</creatorcontrib><creatorcontrib>Veneziano, Claudia</creatorcontrib><creatorcontrib>Longhini, Federico</creatorcontrib><creatorcontrib>Bruni, Andrea</creatorcontrib><creatorcontrib>Garofalo, Eugenio</creatorcontrib><creatorcontrib>Pantanella, Marta</creatorcontrib><creatorcontrib>Manno, Michele</creatorcontrib><creatorcontrib>Gigliotti, Simona</creatorcontrib><creatorcontrib>Giancotti, Aida</creatorcontrib><creatorcontrib>Barreca, Giorgio Settimo</creatorcontrib><creatorcontrib>Branda, Francesco</creatorcontrib><creatorcontrib>Torti, Carlo</creatorcontrib><creatorcontrib>Rotundo, Salvatore</creatorcontrib><creatorcontrib>Lionello, Rosaria</creatorcontrib><creatorcontrib>La Gamba, Valentina</creatorcontrib><creatorcontrib>Berardelli, Lavinia</creatorcontrib><creatorcontrib>Gullì, Sara Palma</creatorcontrib><creatorcontrib>Trecarichi, Enrico Maria</creatorcontrib><creatorcontrib>Russo, Alessandro</creatorcontrib><creatorcontrib>Palmieri, Camillo</creatorcontrib><creatorcontrib>De Marco, Carmela</creatorcontrib><creatorcontrib>Viglietto, Giuseppe</creatorcontrib><creatorcontrib>Casu, Marco</creatorcontrib><creatorcontrib>Sanna, Daria</creatorcontrib><creatorcontrib>Ciccozzi, Massimo</creatorcontrib><creatorcontrib>Scarpa, Fabio</creatorcontrib><creatorcontrib>Matera, Giovanni</creatorcontrib><title>Persistence of SARS‐CoV‐2 infection and viral intra‐ and inter‐host evolution in COVID‐19 hospitalized patients</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) persistence in COVID‐19 patients could play a key role in the emergence of variants of concern. The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID‐19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID‐19 patients with persistent SARS‐CoV‐2 infection, from January 2022 to March 2023, was conducted. To characterize the intra‐ and inter‐host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS‐CoV‐2 intra‐host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host‐based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro‐active genomic surveillance of persistent SARS‐CoV‐2 infected patients is recommended to identify genetically divergent lineages before their diffusion.</description><subject>Adult</subject><subject>Aged</subject><subject>Bayes Theorem</subject><subject>Bayesian analysis</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - epidemiology</subject><subject>COVID-19 - transmission</subject><subject>COVID-19 - virology</subject><subject>Divergence</subject><subject>Evolution</subject><subject>Evolution, Molecular</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>Genome, Viral - genetics</subject><subject>Genomic analysis</subject><subject>Glycoproteins</subject><subject>Hospitalization</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectivity</subject><subject>inter‐host viral genetic evolution</subject><subject>intra‐host viral genetic evolution</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nasopharynx - virology</subject><subject>Persistent infection</subject><subject>phylodynamic analysis</subject><subject>phylogenetic analysis</subject><subject>Phylogenetics</subject><subject>Phylogeny</subject><subject>Respiratory diseases</subject><subject>Retrospective Studies</subject><subject>SARS-CoV-2 - classification</subject><subject>SARS-CoV-2 - genetics</subject><subject>SARS‐CoV‐2 immune escape mutations</subject><subject>SARS‐CoV‐2 persistence</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus - genetics</subject><subject>Statistical inference</subject><subject>Viral diseases</subject><subject>Whole Genome Sequencing</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9uEzEQxi1ERdLAgRdAlrjQw6Zj767_HKMA_aOgIgq5rhzvrHC0WQd7NyiceIQ-Y5-kblI4IHGZ0cz306cZfYS8ZjBlAPx8vdlNuZagnpExAy0yDZI9J2NghciEYOWInMa4BgClOX9BRrlSUDCpx2T_GUN0scfOIvUNvZ19ub3_fTf3y1Q5dV2Dtne-o6ar6c4F06ZdH0xSD6s0YEjDdx97ijvfDgfadXR-s7x6nxSmaRK3rjet-4U13ZreYdfHl-SkMW3EV099Qr59_PB1fpktbi6u5rNFZnmRq6wGvSq5XOUWjS5WutQANj1mi0aaXHHQqhFaC40FcKxLqXjZ2AKFlZLL0uYT8u7ouw3-x4CxrzYuWmxb06EfYpWDYCwXSsqEvv0HXfshdOm6REleKMnTTRNydqRs8DEGbKptcBsT9hWD6jGPKuVRHfJI7Jsnx2G1wfov-SeABJwfgZ-uxf3_narrT8uj5QPN4Zfy</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Pavia, Grazia</creator><creator>Quirino, Angela</creator><creator>Marascio, Nadia</creator><creator>Veneziano, Claudia</creator><creator>Longhini, Federico</creator><creator>Bruni, Andrea</creator><creator>Garofalo, Eugenio</creator><creator>Pantanella, Marta</creator><creator>Manno, Michele</creator><creator>Gigliotti, Simona</creator><creator>Giancotti, Aida</creator><creator>Barreca, Giorgio Settimo</creator><creator>Branda, Francesco</creator><creator>Torti, Carlo</creator><creator>Rotundo, Salvatore</creator><creator>Lionello, Rosaria</creator><creator>La Gamba, Valentina</creator><creator>Berardelli, Lavinia</creator><creator>Gullì, Sara Palma</creator><creator>Trecarichi, Enrico Maria</creator><creator>Russo, Alessandro</creator><creator>Palmieri, Camillo</creator><creator>De Marco, Carmela</creator><creator>Viglietto, Giuseppe</creator><creator>Casu, Marco</creator><creator>Sanna, Daria</creator><creator>Ciccozzi, Massimo</creator><creator>Scarpa, Fabio</creator><creator>Matera, Giovanni</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3501-714X</orcidid><orcidid>https://orcid.org/0000-0001-7631-5453</orcidid><orcidid>https://orcid.org/0000-0003-3866-9239</orcidid></search><sort><creationdate>202406</creationdate><title>Persistence of SARS‐CoV‐2 infection and viral intra‐ and inter‐host evolution in COVID‐19 hospitalized patients</title><author>Pavia, Grazia ; Quirino, Angela ; Marascio, Nadia ; Veneziano, Claudia ; Longhini, Federico ; Bruni, Andrea ; Garofalo, Eugenio ; Pantanella, Marta ; Manno, Michele ; Gigliotti, Simona ; Giancotti, Aida ; Barreca, Giorgio Settimo ; Branda, Francesco ; Torti, Carlo ; Rotundo, Salvatore ; Lionello, Rosaria ; La Gamba, Valentina ; Berardelli, Lavinia ; Gullì, Sara Palma ; Trecarichi, Enrico Maria ; Russo, Alessandro ; Palmieri, Camillo ; De Marco, Carmela ; Viglietto, Giuseppe ; Casu, Marco ; Sanna, Daria ; Ciccozzi, Massimo ; Scarpa, Fabio ; Matera, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2438-d09b527b3cea94b95900c014c4f7a382098f69969e402ed57825fc4e6c77275c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Bayes Theorem</topic><topic>Bayesian analysis</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - 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The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID‐19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID‐19 patients with persistent SARS‐CoV‐2 infection, from January 2022 to March 2023, was conducted. To characterize the intra‐ and inter‐host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS‐CoV‐2 intra‐host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host‐based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro‐active genomic surveillance of persistent SARS‐CoV‐2 infected patients is recommended to identify genetically divergent lineages before their diffusion.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38804179</pmid><doi>10.1002/jmv.29708</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-3501-714X</orcidid><orcidid>https://orcid.org/0000-0001-7631-5453</orcidid><orcidid>https://orcid.org/0000-0003-3866-9239</orcidid><oa>free_for_read</oa></addata></record> |
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identifier | ISSN: 0146-6615 |
ispartof | Journal of medical virology, 2024-06, Vol.96 (6), p.e29708-n/a |
issn | 0146-6615 1096-9071 |
language | eng |
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source | MEDLINE; Access via Wiley Online Library |
subjects | Adult Aged Bayes Theorem Bayesian analysis Coronaviruses COVID-19 COVID-19 - epidemiology COVID-19 - transmission COVID-19 - virology Divergence Evolution Evolution, Molecular Female Gene sequencing Genome, Viral - genetics Genomic analysis Glycoproteins Hospitalization Humans Infections Infectivity inter‐host viral genetic evolution intra‐host viral genetic evolution Longitudinal Studies Male Middle Aged Nasopharynx - virology Persistent infection phylodynamic analysis phylogenetic analysis Phylogenetics Phylogeny Respiratory diseases Retrospective Studies SARS-CoV-2 - classification SARS-CoV-2 - genetics SARS‐CoV‐2 immune escape mutations SARS‐CoV‐2 persistence Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - genetics Statistical inference Viral diseases Whole Genome Sequencing |
title | Persistence of SARS‐CoV‐2 infection and viral intra‐ and inter‐host evolution in COVID‐19 hospitalized patients |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T06%3A34%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Persistence%20of%20SARS%E2%80%90CoV%E2%80%902%20infection%20and%20viral%20intra%E2%80%90%20and%20inter%E2%80%90host%20evolution%20in%20COVID%E2%80%9019%20hospitalized%20patients&rft.jtitle=Journal%20of%20medical%20virology&rft.au=Pavia,%20Grazia&rft.date=2024-06&rft.volume=96&rft.issue=6&rft.spage=e29708&rft.epage=n/a&rft.pages=e29708-n/a&rft.issn=0146-6615&rft.eissn=1096-9071&rft_id=info:doi/10.1002/jmv.29708&rft_dat=%3Cproquest_cross%3E3072487224%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3072487224&rft_id=info:pmid/38804179&rfr_iscdi=true |