Clinical and virological course of infection with haemagglutinin D222G mutant strain of 2009 pandemic influenza A (H1N1) virus

Abstract

Background: Aspartic acid to glycine substitution (D222G) of haemagglutinin subunit (HA1) was associated with adverse outcomes in 2009 pandemic influenza A (H1N1) infections.

Objectives: To characterize the virological profile and antiviral response of patients infected with the HA1 D222G mutant.

Study design: Sixty-three adults admitted for pandemic influenza in Hong Kong were tested for D222G mutation by direct sequencing. Nasopharyngeal viral concentration on presentation was measured by real-time PCR to evaluate shedding from the upper respiratory tract. Serial upper and lower respiratory tract specimens were monitored to determine preferential tropism and document virological response to treatment.

Results: The frequency of D222G infection was 17.4% among cases with severe pneumonia, and 26.7% among cases requiring intensive care. Altogether, four sporadic D222G cases spread across the first and second waves in Hong Kong were detected. A significant association between D222G infection with severe pneumonia (100% vs. 32.2%, P=0.015) and intensive care admission (100% vs. 18.6%, P=0.002) was observed. D222G was associated with lower concentrations of virus in the upper respiratory tract compared to wildtype, but persisted in the lower respiratory tract at high concentrations, despite clearance from the upper respiratory tract following antiviral treatment.

Conclusions: These observations suggest that D222G can arise de novo, sheds less virus from the upper respiratory tract and may be less transmissible, but more pneumotropic and more resistant to antiviral treatment. D222G is associated with a higher chance of developing critical disease. Lower respiratory tract specimen is needed for a reliable detection of this mutant.