Severe outcome of influenza A/H1N1/09v infection associated with 222G/N polymorphisms in the haemagglutinin: a multicenter study.

In a multicenter study influenza A/H1N1/09v 222G/N variants were more frequently detected in patients admitted to intensive care unit (ICU) for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) (10/23; 43.5\%) than in patients hospitalized in other units (2/27; 7.4\%) and community patients (0/81; 0.0\%) (p<0.01). A significantly higher virus load (p=0.02) in the lower vs upper respiratory tract was observed. Predominance of 222G/N variants in the lower respiratory tract (40\% of total virus population) vs upper respiratory tract (10\%) was shown by clonal analysis of HA sequences in paired nasal swab and bronchoalveolar lavage samples. The time from illness onset to sampling was significantly longer in patients with severe infection vs community patients (p<0.001). Conclusions: i) 222G/N variants showed increased virulence; ii) mutant variants were likely selected in individual patients, iii) the longer duration of illness might have favored the emergence of adaptive mutations through multiple replication cycles.