Title Clinical and virological factors associated with viremia inpandemic influenza A / H 1 N 1 / 2009 virus infection

Background: Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings: Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reversetranscription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/ 2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion: Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. Citation: Tse H, To KKW, Wen X, Chen H, Chan K-H, et al. (2011) Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection. PLoS ONE 6(9): e22534. doi:10.1371/journal.pone. 0022534 Editor: Philip J. Norris, Blood Systems Research Institute, United States of America Received April 19, 2011; Accepted June 23, 2011; Published September 27, 2011 Copyright: 2011 Tse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: We gratefully acknowledge funding support from the Providence Foundation Limited in memory of the late Dr Lui Hac Minh, the University Grants Council, and the Research Fund for the Control of Infectious Diseases (RFCID) of the Food and Health Bureau of the Hong Kong SAR Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: We gratefully acknowledge funding support from the Providence Foundation Limited in memory of the late Dr Lui Hac Minh, the University Grants Council. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. * E-mail: kyyuen@hkucc.hku. hk