A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection
Background In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potentia...
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| Veröffentlicht in: | Influenza and other respiratory viruses 2013-11, Vol.7 (6), p.1416-1426 |
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| creator | Ruggiero, Tina De Rosa, Francesco Cerutti, Francesco Pagani, Nicole Allice, Tiziano Stella, Maria L. Milia, Maria G. Calcagno, Andrea Burdino, Elisa Gregori, Gabriella Urbino, Rosario Di Perri, Giovanni Ranieri, Marco V. Ghisetti, Valeria |
| description | Background
In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.
Objectives
To assess the contribution of HA‐RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009–2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.
Patients and methods
We retrospectively analyzed HA‐RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.
Results
By HA‐RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n = 8/24, 33·3%) than in patients with mild disease (n = 2/34, 6%) or in outpatients (n = 0/44) (Fisher's exact test P |
| doi_str_mv | 10.1111/irv.12146 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_24P</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4634302</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1464512809</sourcerecordid><originalsourceid>FETCH-LOGICAL-j4406-72325bfc7239e3a4e96804395ea62c0fbe7373c72974ee43031a35a799b25a6d3</originalsourceid><addsrcrecordid>eNqNkk1v1DAQhiMEoqVw4A8gH8thW38m6wtSVeiHVBUJAVdrkkyyrhI72NnQ_Mb-KZxtWdEbvnjk99E745nJsveMnrB0Tm2YThhnMn-RHbJC0RXPlX65jyU9yN7EeEepytdKvs4OuNC8KJg4zB7Ojq_YLfs41D3VZIM9tG23Ha2zjnzmnF8ScPUuuiUTBAtujAQCkibgry26sZvJBkLpA9aknMkAo8WFWWQbrGsJ3o8BKh-GxEBHeuzLAA6Jv59bdIn3bpcE6glclWwCxsEGGH2YCcRo47i8k8YHEnHClPxZ0dY1WC0ub7NXDXQR3z3dR9mPiy_fz69WN18vr8_PblZ3UtJ8VXDBVdlU6dYoQKLO11QKrRByXtGmxEIUIsm6kIhSUMFAKCi0LrmCvBZH2adH32Fb9lhX6b8BOjME20OYjQdrnivObkzrJyNzkex4Mjh-Mgg-NTGOprexwq5LbfHbaNIkpWJ8TfV_oHIZpcplQj_8W9a-nr_DTsDpI_DbdjjvdUbNskUmbZHZbZG5_vZzF4g_giW8aQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1449277564</pqid></control><display><type>article</type><title>A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection</title><source>Wiley Online Library Open Access</source><creator>Ruggiero, Tina ; De Rosa, Francesco ; Cerutti, Francesco ; Pagani, Nicole ; Allice, Tiziano ; Stella, Maria L. ; Milia, Maria G. ; Calcagno, Andrea ; Burdino, Elisa ; Gregori, Gabriella ; Urbino, Rosario ; Di Perri, Giovanni ; Ranieri, Marco V. ; Ghisetti, Valeria</creator><creatorcontrib>Ruggiero, Tina ; De Rosa, Francesco ; Cerutti, Francesco ; Pagani, Nicole ; Allice, Tiziano ; Stella, Maria L. ; Milia, Maria G. ; Calcagno, Andrea ; Burdino, Elisa ; Gregori, Gabriella ; Urbino, Rosario ; Di Perri, Giovanni ; Ranieri, Marco V. ; Ghisetti, Valeria</creatorcontrib><description>Background
In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.
Objectives
To assess the contribution of HA‐RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009–2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.
Patients and methods
We retrospectively analyzed HA‐RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.
Results
By HA‐RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n = 8/24, 33·3%) than in patients with mild disease (n = 2/34, 6%) or in outpatients (n = 0/44) (Fisher's exact test P < 0·0001; OR 38·5; CI 95% 4·494–329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples.
Conclusions
A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus–host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.</description><identifier>ISSN: 1750-2640</identifier><identifier>EISSN: 1750-2659</identifier><identifier>DOI: 10.1111/irv.12146</identifier><identifier>PMID: 23927713</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>A(H1N1)pdm09 virus ; Adaptations ; Adult ; Aged ; Aged, 80 and over ; Critical Care - statistics & numerical data ; Extracorporeal Membrane Oxygenation - statistics & numerical data ; extracorporeal membrane oxygenation and influenza ; Female ; hemagglutinin D222G and D222N variants ; Hemagglutinin Glycoproteins, Influenza Virus - genetics ; Humans ; Influenza A Virus, H1N1 Subtype - genetics ; Influenza A Virus, H1N1 Subtype - isolation & purification ; Influenza A Virus, H1N1 Subtype - pathogenicity ; Influenza, Human - complications ; Influenza, Human - pathology ; Influenza, Human - therapy ; Influenza, Human - virology ; Italy ; Male ; Middle Aged ; Molecular Sequence Data ; Mutant Proteins - genetics ; Mutation, Missense ; Original ; Part 5 ; Polymorphism, Genetic ; Respiratory Distress Syndrome - therapy ; Retrospective Studies ; Sequence Analysis, DNA ; Virulence Factors - genetics ; Young Adult</subject><ispartof>Influenza and other respiratory viruses, 2013-11, Vol.7 (6), p.1416-1426</ispartof><rights>2013 John Wiley & Sons Ltd</rights><rights>2013 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634302/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634302/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Firv.12146$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23927713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruggiero, Tina</creatorcontrib><creatorcontrib>De Rosa, Francesco</creatorcontrib><creatorcontrib>Cerutti, Francesco</creatorcontrib><creatorcontrib>Pagani, Nicole</creatorcontrib><creatorcontrib>Allice, Tiziano</creatorcontrib><creatorcontrib>Stella, Maria L.</creatorcontrib><creatorcontrib>Milia, Maria G.</creatorcontrib><creatorcontrib>Calcagno, Andrea</creatorcontrib><creatorcontrib>Burdino, Elisa</creatorcontrib><creatorcontrib>Gregori, Gabriella</creatorcontrib><creatorcontrib>Urbino, Rosario</creatorcontrib><creatorcontrib>Di Perri, Giovanni</creatorcontrib><creatorcontrib>Ranieri, Marco V.</creatorcontrib><creatorcontrib>Ghisetti, Valeria</creatorcontrib><title>A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection</title><title>Influenza and other respiratory viruses</title><addtitle>Influenza Other Respir Viruses</addtitle><description>Background
In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.
Objectives
To assess the contribution of HA‐RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009–2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.
Patients and methods
We retrospectively analyzed HA‐RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.
Results
By HA‐RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n = 8/24, 33·3%) than in patients with mild disease (n = 2/34, 6%) or in outpatients (n = 0/44) (Fisher's exact test P < 0·0001; OR 38·5; CI 95% 4·494–329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples.
Conclusions
A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus–host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.</description><subject>A(H1N1)pdm09 virus</subject><subject>Adaptations</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Critical Care - statistics & numerical data</subject><subject>Extracorporeal Membrane Oxygenation - statistics & numerical data</subject><subject>extracorporeal membrane oxygenation and influenza</subject><subject>Female</subject><subject>hemagglutinin D222G and D222N variants</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - genetics</subject><subject>Humans</subject><subject>Influenza A Virus, H1N1 Subtype - genetics</subject><subject>Influenza A Virus, H1N1 Subtype - isolation & purification</subject><subject>Influenza A Virus, H1N1 Subtype - pathogenicity</subject><subject>Influenza, Human - complications</subject><subject>Influenza, Human - pathology</subject><subject>Influenza, Human - therapy</subject><subject>Influenza, Human - virology</subject><subject>Italy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutant Proteins - genetics</subject><subject>Mutation, Missense</subject><subject>Original</subject><subject>Part 5</subject><subject>Polymorphism, Genetic</subject><subject>Respiratory Distress Syndrome - therapy</subject><subject>Retrospective Studies</subject><subject>Sequence Analysis, DNA</subject><subject>Virulence Factors - genetics</subject><subject>Young Adult</subject><issn>1750-2640</issn><issn>1750-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk1v1DAQhiMEoqVw4A8gH8thW38m6wtSVeiHVBUJAVdrkkyyrhI72NnQ_Mb-KZxtWdEbvnjk99E745nJsveMnrB0Tm2YThhnMn-RHbJC0RXPlX65jyU9yN7EeEepytdKvs4OuNC8KJg4zB7Ojq_YLfs41D3VZIM9tG23Ha2zjnzmnF8ScPUuuiUTBAtujAQCkibgry26sZvJBkLpA9aknMkAo8WFWWQbrGsJ3o8BKh-GxEBHeuzLAA6Jv59bdIn3bpcE6glclWwCxsEGGH2YCcRo47i8k8YHEnHClPxZ0dY1WC0ub7NXDXQR3z3dR9mPiy_fz69WN18vr8_PblZ3UtJ8VXDBVdlU6dYoQKLO11QKrRByXtGmxEIUIsm6kIhSUMFAKCi0LrmCvBZH2adH32Fb9lhX6b8BOjME20OYjQdrnivObkzrJyNzkex4Mjh-Mgg-NTGOprexwq5LbfHbaNIkpWJ8TfV_oHIZpcplQj_8W9a-nr_DTsDpI_DbdjjvdUbNskUmbZHZbZG5_vZzF4g_giW8aQ</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Ruggiero, Tina</creator><creator>De Rosa, Francesco</creator><creator>Cerutti, Francesco</creator><creator>Pagani, Nicole</creator><creator>Allice, Tiziano</creator><creator>Stella, Maria L.</creator><creator>Milia, Maria G.</creator><creator>Calcagno, Andrea</creator><creator>Burdino, Elisa</creator><creator>Gregori, Gabriella</creator><creator>Urbino, Rosario</creator><creator>Di Perri, Giovanni</creator><creator>Ranieri, Marco V.</creator><creator>Ghisetti, Valeria</creator><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201311</creationdate><title>A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection</title><author>Ruggiero, Tina ; De Rosa, Francesco ; Cerutti, Francesco ; Pagani, Nicole ; Allice, Tiziano ; Stella, Maria L. ; Milia, Maria G. ; Calcagno, Andrea ; Burdino, Elisa ; Gregori, Gabriella ; Urbino, Rosario ; Di Perri, Giovanni ; Ranieri, Marco V. ; Ghisetti, Valeria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j4406-72325bfc7239e3a4e96804395ea62c0fbe7373c72974ee43031a35a799b25a6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>A(H1N1)pdm09 virus</topic><topic>Adaptations</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Critical Care - statistics & numerical data</topic><topic>Extracorporeal Membrane Oxygenation - statistics & numerical data</topic><topic>extracorporeal membrane oxygenation and influenza</topic><topic>Female</topic><topic>hemagglutinin D222G and D222N variants</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - genetics</topic><topic>Humans</topic><topic>Influenza A Virus, H1N1 Subtype - genetics</topic><topic>Influenza A Virus, H1N1 Subtype - isolation & purification</topic><topic>Influenza A Virus, H1N1 Subtype - pathogenicity</topic><topic>Influenza, Human - complications</topic><topic>Influenza, Human - pathology</topic><topic>Influenza, Human - therapy</topic><topic>Influenza, Human - virology</topic><topic>Italy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutant Proteins - genetics</topic><topic>Mutation, Missense</topic><topic>Original</topic><topic>Part 5</topic><topic>Polymorphism, Genetic</topic><topic>Respiratory Distress Syndrome - therapy</topic><topic>Retrospective Studies</topic><topic>Sequence Analysis, DNA</topic><topic>Virulence Factors - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruggiero, Tina</creatorcontrib><creatorcontrib>De Rosa, Francesco</creatorcontrib><creatorcontrib>Cerutti, Francesco</creatorcontrib><creatorcontrib>Pagani, Nicole</creatorcontrib><creatorcontrib>Allice, Tiziano</creatorcontrib><creatorcontrib>Stella, Maria L.</creatorcontrib><creatorcontrib>Milia, Maria G.</creatorcontrib><creatorcontrib>Calcagno, Andrea</creatorcontrib><creatorcontrib>Burdino, Elisa</creatorcontrib><creatorcontrib>Gregori, Gabriella</creatorcontrib><creatorcontrib>Urbino, Rosario</creatorcontrib><creatorcontrib>Di Perri, Giovanni</creatorcontrib><creatorcontrib>Ranieri, Marco V.</creatorcontrib><creatorcontrib>Ghisetti, Valeria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Influenza and other respiratory viruses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Ruggiero, Tina</au><au>De Rosa, Francesco</au><au>Cerutti, Francesco</au><au>Pagani, Nicole</au><au>Allice, Tiziano</au><au>Stella, Maria L.</au><au>Milia, Maria G.</au><au>Calcagno, Andrea</au><au>Burdino, Elisa</au><au>Gregori, Gabriella</au><au>Urbino, Rosario</au><au>Di Perri, Giovanni</au><au>Ranieri, Marco V.</au><au>Ghisetti, Valeria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection</atitle><jtitle>Influenza and other respiratory viruses</jtitle><addtitle>Influenza Other Respir Viruses</addtitle><date>2013-11</date><risdate>2013</risdate><volume>7</volume><issue>6</issue><spage>1416</spage><epage>1426</epage><pages>1416-1426</pages><issn>1750-2640</issn><eissn>1750-2659</eissn><abstract>Background
In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.
Objectives
To assess the contribution of HA‐RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009–2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.
Patients and methods
We retrospectively analyzed HA‐RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.
Results
By HA‐RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n = 8/24, 33·3%) than in patients with mild disease (n = 2/34, 6%) or in outpatients (n = 0/44) (Fisher's exact test P < 0·0001; OR 38·5; CI 95% 4·494–329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples.
Conclusions
A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus–host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>23927713</pmid><doi>10.1111/irv.12146</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | A(H1N1)pdm09 virus Adaptations Adult Aged Aged, 80 and over Critical Care - statistics & numerical data Extracorporeal Membrane Oxygenation - statistics & numerical data extracorporeal membrane oxygenation and influenza Female hemagglutinin D222G and D222N variants Hemagglutinin Glycoproteins, Influenza Virus - genetics Humans Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - isolation & purification Influenza A Virus, H1N1 Subtype - pathogenicity Influenza, Human - complications Influenza, Human - pathology Influenza, Human - therapy Influenza, Human - virology Italy Male Middle Aged Molecular Sequence Data Mutant Proteins - genetics Mutation, Missense Original Part 5 Polymorphism, Genetic Respiratory Distress Syndrome - therapy Retrospective Studies Sequence Analysis, DNA Virulence Factors - genetics Young Adult |
| title | A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection |
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