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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Veröffentlicht in:Journal of medical virology 2024-06, Vol.96 (6), p.e29708-n/a
Hauptverfasser: 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
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container_issue 6
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container_title Journal of medical virology
container_volume 96
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. 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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><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 ; 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Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavia, Grazia</au><au>Quirino, Angela</au><au>Marascio, Nadia</au><au>Veneziano, Claudia</au><au>Longhini, Federico</au><au>Bruni, Andrea</au><au>Garofalo, Eugenio</au><au>Pantanella, Marta</au><au>Manno, Michele</au><au>Gigliotti, Simona</au><au>Giancotti, Aida</au><au>Barreca, Giorgio Settimo</au><au>Branda, Francesco</au><au>Torti, Carlo</au><au>Rotundo, Salvatore</au><au>Lionello, Rosaria</au><au>La Gamba, Valentina</au><au>Berardelli, Lavinia</au><au>Gullì, Sara Palma</au><au>Trecarichi, Enrico Maria</au><au>Russo, Alessandro</au><au>Palmieri, Camillo</au><au>De Marco, Carmela</au><au>Viglietto, Giuseppe</au><au>Casu, Marco</au><au>Sanna, Daria</au><au>Ciccozzi, Massimo</au><au>Scarpa, Fabio</au><au>Matera, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Persistence of SARS‐CoV‐2 infection and viral intra‐ and inter‐host evolution in COVID‐19 hospitalized patients</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2024-06</date><risdate>2024</risdate><volume>96</volume><issue>6</issue><spage>e29708</spage><epage>n/a</epage><pages>e29708-n/a</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>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.</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
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issn 0146-6615
1096-9071
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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
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