title: Segregation of virulent influenza A(H1N1) variants in the lower respiratory tract of critically ill patients during the 2010-2011 seasonal epidemic.
abstract: BACKGROUND
  Since its appearance in 2009, the pandemic influenza A(H1N1) virus circulated worldwide causing several severe infections.
  
  
  METHODS
  Respiratory samples from patients with 2009 influenza A(H1N1) and acute respiratory distress attending 24 intensive care units (ICUs) as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants) of Italy during the 2010-2011 winter-spring season, were analyzed.
  
  
  RESULTS
  In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL) with respect to nasal swab (NS), (p<0.001) suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D) circulated simultaneously. Most (72.7%, n = 48) of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26) or moderate ILI (n = 22). Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D) were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples.
  
  
  CONCLUSIONS
  Multiple virus clusters co-circulated during the 2010-2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1) variants, which replicated preferentially in the lower respiratory tract.
authors.affiliation: Struttura Semplice Virologia Molecolare, Fondazione Istituto Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piralla
authors.forename: Elena
authors.initials: E
authors.lastname: Pariani
authors.forename: Francesca
authors.initials: F
authors.lastname: Rovida
authors.forename: Giulia
authors.initials: G
authors.lastname: Campanini
authors.forename: Alba
authors.initials: A
authors.lastname: Muzzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Emmi
authors.forename: Giorgio A
authors.initials: GA
authors.lastname: Iotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Pesenti
authors.forename: Pier Giulio
authors.initials: PG
authors.lastname: Conaldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zanetti
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000453:epidemiology*; D058872:Epidemics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D012137:Respiratory System / Q000821:virology*; D012621:Seasons; D014774:Virulence; D055815:Young Adult
chemical_list: D011991:Receptors, Virus