UN acquired the data from the TR-DGU, performed the statistical analysis and contributed to writing the manuscript. MM contributed to acquiring the data from the TR-DGU and to writing the manuscript. GH contributed to designing the study, analysing the data and writing the manuscript. FP, BS and CA acquired the data from the STC. AH, WV and CJ contributed to unfortunately writing the manuscript. CS contributed to designing the study, analysing the data, and writing the manuscript. All authors read and approved the final manuscript.NotesSee related letter by David et al., http://ccforum.com/content/15/3/433AcknowledgementsEditorial assistance was provided by Ken Sutor of Fishawack Communications Ltd. during late-stage development of this manuscript. Financial support for this assistance was provided by CSL Behring GmbH.

In the spring of 2009, novel human influenza A (H1N1) (A/H1N1/2009) infection began spreading from Mexico around the globe, causing a worldwide pandemic [1-3]. Contrary to initial fears, most patients experienced a mild clinical course. Some patients did become critically ill with respiratory failure, however, requiring intensive care and ventilator support. Mortality rates were high in these patients, especially in those who developed multiorgan failure [4-6].The mechanisms leading to multiorgan failure and death in patients with influenza infection are not well understood. Septicemia is a leading cause of seasonal influenza, mainly due to secondary infection by other microorganisms, principally Gram-positive or Gram-negative bacteria.

The first reports of fatal A/H1N1/2009 infections, however, only described septicemia occasionally [7,8]. Other pathomechanisms may also contribute to severe multiorgan failure, with several reports suggesting that patients with severe influenza infection may develop a virus-associated hemophagocytic syndrome (VAHS) [8-10].VAHS may present as an aggressive, life-threatening disease, with previous reports implicating its role in fatal cases of seasonal (H3N2) influenza as well as avian (H5N1) influenza virus [8,9,11]. Analogously to hereditary hemophagocytic lymphohistiocytosis (HLH), VAHS is associated with massive cytokine release (“cytokine storm”), elevated plasma levels of soluble interleukin 2 receptor (sIL-2R) and other inflammatory mediators and the accumulation of activated T-lymphocytes and macrophages in various organs, frequently resulting in multiorgan failure and death [12-16].

In Germany, peak infection rates for A/H1N1/2009 occurred between October 2009 and December 2009, that is, in the first winter season after the initial outbreak in Mexico. In Cilengitide our tertiary care center, the first critically ill patient with A/H1N1/2009 infection and respiratory failure was admitted on 5 October 2009. This patient required mechanical ventilation and extracorporeal membrane oxygenation (ECMO) for 2 weeks.