深圳市罗湖区住院病人新型甲型H1N1流感感染情况分析

目的分析深圳市罗湖区住院病人新型甲型H1N1流感的感染情况,为辖区住院病人的甲流防控工作提供依据。方法采用描述性流行病学研究方法对深圳市罗湖区2009年11月至2010年2月期间深圳市人民医院和罗湖区人民医院的住院病人新型甲型H1N1流感的感染情况进行分析。结果在2009年11月至2010年2月期间共检测了292份疑似甲流的住院病人的咽拭子样本,共检出甲流感染者93例。2009年11月份住院病人感染甲流的人数最多,感染率高达68.18%。30岁以下的住院病人感染甲流的人数占住院病人感染甲流总数的81.7%。男女住院病人甲流的感染率比为1.21：1.结论甲流主要感染30岁以下住院病人,因此,需要加强对该年龄段有流感症状的住院病人的甲流排查和管理。     

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

In a multicentre study, influenza A/H1N1/09v 222G/N variants were more frequently detected in patients admitted to the intensive-care unit for invasive mechanical ventilation or extracorporeal membrane oxygenation (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 the upper respiratory tract was observed. Predominance of 222G/N variants in the lower respiratory tract (40% of total virus population) vs the upper respiratory tract (10%) was shown by clonal analysis of haemagglutinin 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). It was concluded that the 222G/N variants showed increased virulence; mutant variants were probably selected in individual patients; and the longer duration of illness might have favoured the emergence of adaptive mutations through multiple replication cycles.     

Characterization of oseltamivir‐resistant influenza A(H1N1)pdm09 viruses in Taiwan in 2009–2011

The early isolated swine‐origin influenza A(H1N1)pdm09 viruses were susceptible to oseltamivir; however, there is a concern about whether oseltamivir‐resistant influenza A(H1N1)pdm09 viruses will spread worldwide as did the oseltamivir‐resistant seasonal influenza A(H1N1) viruses in 2007–2008. In this study, the frequency of oseltamivir resistance in influenza A(H1N1)pdm09 viruses was determined in Taiwan. From May 2009 to April 2011, 1,335 A(H1N1)pdm09‐positive cases in Taiwan were tested for the H275Y mutation in the neuraminidase (NA) gene that confers resistance to oseltamivir. Among these, 15 patients (1.1%) were found to be infected with H275Y virus. All the resistant viruses were detected after the patients have received the oseltamivir. The overall monthly ratio of H275Y‐harboring viruses ranged between 0% and 2.88%, and the peak was correlated with influenza epidemics. The genetic analysis revealed that the oseltamivir‐resistant A(H1N1)pdm09 viruses can emerged from different variants with a great diversity under drug pressure. The ratio of NA/HA activities in different clades of oseltamivir‐resistant viruses was reduced compared to those in the wild‐type viruses, indicating that the balance of NA/HA in the current oseltamivir‐resistant influenza A(H1N1)pdm09 viruses was interfered. It is possible that H275Y‐bearing A(H1N1)pdm09 virus has not yet spread globally because it lacks the essential permissive mutations that can compensate for the negative impact on fitness by the H275Y amino acid substitution in NA. Continuous monitoring the evolution patterns of sensitive and resistant viruses is required to respond to possible emergence of resistant viruses with permissive genetic background which enable the wide spread of resistance. J. Med. Virol. 85:379–387, 2013. © 2012 Wiley Periodicals, Inc.     

Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus

BackgroundDespite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny.Study designWe document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09.ResultsComplete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID₅₀ of 10⁴/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia.ConclusionsIt is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities.     

Monoclonal antibodies to the haemagglutinin HA1 subunit of the pandemic influenza A/H1N1 2009 virus and potential application to serodiagnosis

In order to provide specific serological reagents for pandemic influenza A/H1N1 2009 virus, monoclonal antibodies (Mabs) to recombinant haemagglutinin component HA1 (rHA1) were generated after fusing spleen cells from a mouse immunized with rHA1 protein derived from influenza strain A/California/06/09 H1N1 with a mouse myeloma cell line. Five hybridoma clones secreting Mabs specific for the rHA1 protein derived from pandemic influenza A/H1N1 2009 and not for rHA1 from seasonal H1N1 influenza strains A/Brisbane/59/07 and A/Solomon Islands/03/06 were identified by EIA. Mabs 7H4, 9A4, and 9E12 were reactive in Western blots with full length rHA and/or rHA1 subunit derived from A/California/06/09 strain. Only Mab 1F5 inhibited haemagglutination of turkey red blood cells with recombinant NIBRG‐121 virus derived from A/California/07/09, but did not react in Western blots. Immunostaining of MDCK cells infected with NIBRG‐121 was localized to the membrane/cytoplasm for four of the reactive Mabs. The differing reactivity of the Mabs in Western blots, immunostaining, EIA, and haemagglutination inhibition assay suggest that at least four of the five Mabs recognize different epitopes on HA1 of the pandemic influenza A/H1N1 2009 virus. Ferret antisera to pandemic influenza A/H1N1 2009 (A/England/195/09 and A/California/07/09 strains) and sera from human subjects vaccinated with Influenza A (H1N1) 2009 Monovalent Vaccine (CELTURA®, Novartis Vaccines, Germany), inhibit binding of 1F5‐HRP to biotinylated rHA1 derived from A/California/06/09 in a competitive EIA, suggesting that the epitope recognized by this Mab also evokes an antibody response in infected ferrets and vaccinated humans. J. Med. Virol. 83:559–567, 2011. © 2011 Wiley‐Liss, Inc.     

新型甲型H1N1流感的实验室检测特征及分析

目的比较新型甲型H1N1流感、季节性流感及普通上呼吸道感染的实验室检测特征,进一步认识新型甲型H1N1流感的特点并分析产生的可能机制。方法对我院2009年5～7月收治的新型甲型H1N1流感、季节性流感及普通上呼吸道感染病例的入院实验室检测资料进行回顾性分析。结果新型甲型H1N1流感患者入院时平均血钾为（3.43±0.33）mmol/L,低于季节性流感组和普通上呼吸道感染组,甲型H1N1流感中伴有低钾血症（血钾〈3.5mmol/L）者占60.22%,明显高于另外两组,但合并低钾血症者的血钾平均值在三组间并无明显差异;与另两组相比,新型甲型H1N1流感组外周血白细胞、中性粒细胞、CD4＋T细胞计数降低;其他实验室检测指标包括血钠、血钙、血磷、LDH活性、CK活性等在三组间并无统计学差异。结论新型甲型H1N1流感实验室检测特征包括血钾降低、白细胞、中性粒细胞、CD4＋T细胞减少,其中低钾血症是新型甲型H1N1流感的一个显著实验室特征,其发生的具体机制尚待进一步研究。     

Pediatric hospital admissions from influenza A (H1N1) in Brazil: effects of the 2010 vaccination campaign

In 2009, the influenza A (H1N1) virus spread rapidly around the world, causing the first pandemic of the 21^st Century. In 2010, there was a vaccination campaign against this new virus subtype to reduce the morbidity and mortality of the disease in some countries, including Brazil. Herein, we describe the clinical and epidemiological characteristics of patients under 19 years of age who were hospitalized with confirmed influenza A (H1N1) infection in 2009 and 2010. We retrospectively reviewed files from the pediatric patients who were admitted to a university hospital with real-time polymerase chain reaction (RT-PCR) confirmed influenza A (H1N1) infection in 2009 and 2010. There were 37 hospitalized patients with influenza A (H1N1) in 2009 and 2 in 2010. In 2009, many of the hospitalized children had an underlying chronic disease and a lower median age than those not hospitalized. Of the hospitalized patients, 78% had a chronic disease, primarily pneumopathy (48%). The main signs and symptoms of influenza were fever (97%), cough (76%), and dyspnea (59%). Complications occurred in 81% of the patients. The median length of hospitalization was five days; 27% of the patients required intensive care, and two died. In 2010, two patients were hospitalized with influenza A (H1N1): one infant with adenovirus co-infection who had received one previous H1N1 vaccine dose and presented with respiratory sequelae and a 2-month-old infant who had a hospital-acquired infection. An impressive reduction in hospital admissions was observed in 2010 when the vaccination campaign took place in Brazil.     

A comparison of H1N1 influenza among pediatric inpatients in the pandemic and post pandemic era

BackgroundThe novel influenza A H1N1 (A[H1N1]pdm09) strain emerged in 2009, contributing to significant morbidity and mortality. It is not known whether illness associated with A(H1N1) pdm09 in the post-pandemic era exhibits a similar disease profile.ObjectiveThe objectives of this study were to compare the burden of disease of A(H1N1) pdm09 influenza from the 2009 pandemic year to the post-pandemic years (2010–2014), and to explore potential reasons for any differences.Study designWe conducted a retrospective cohort study of inpatients admitted to Children’s Hospital Colorado with a positive respiratory specimen for influenza from May–December, 2009 and December, 2010–April, 2014. Univariate and multivariate analyses were conducted to compare the demographics and clinical characteristics of patients with H1N1 during the two periods.ResultsThere were 388 inpatients with influenza A(H1N1) pdm09 in 2009, and 117 during the post-pandemic years. Ninety-four percent of all H1N1 during the post-pandemic era was observed during the 2013–2014 influenza season. Patients with A(H1N1) pdm09 during the post-pandemic year were less likely to have an underlying medical condition (P < 0.01). Patients admitted to the ICU during the post-pandemic year had a lower median age (5 vs 8 years, P = 0.01) and a lower proportion of patients were intubated, had mental status changes, and ARDS compared with the pandemic years, (P < 0.01 for all), with decreased mortality (P = 0.02).ConclusionPatients with influenza A(H1N1) pdm09 during the post-pandemic years appeared to have less severe disease than patients with A(H1N1) pdm09 during the pandemic year. The reasons for this difference are likely multifactorial.     

Multiple clusters of A(H1N1)pdm09 virus circulating in severe cases of influenza during the 2010–2011 season: A phylogenetic and molecular analysis of the neuraminidase gene

The molecular characterization of circulating influenza A viruses is crucial to detect mutations potentially involved in increased virulence, drug resistance and immune escape. A molecular and phylogenetic analysis of A(H1N1)pdm09 neuraminidase (NA) gene sequences from different patient categories defined according to the severity of influenza infection were analyzed. A total of 126 influenza A(H1N1)pdm09 positive samples from patients with severe infections in comparison with those with moderate and mild infections was performed in Lombardy (Northern Italy, nearly 10 million inhabitants) during the 2010–2011 season. NA sequences included in this study segregated into five distinct clusters. Nineteen amino acid substitutions were detected exclusively in NA sequences of viruses identified in patients with severe or moderate influenza infection. Three of them (F74S, S79P, E287K) were observed in virus strains with the 222G/N hemagglutinin mutation. None of NA sequences under study had mutations related to the resistance to the NA inhibitors. Four out of 126 (3.2%) NA sequences from patients with severe infection lost a N‐linked glycosylation site due to the change from N to K at residue 386. Two additional N‐linked glycosylation sites in the NA stalk region (residues 42 and 44) were found in 12 (9.5%) NA sequences. Sporadic NA mutations were detected in NA viral sequences from critically ill patients, and no variants with reduced sensitivity to NA inhibitors were observed either in treated or untreated patients. J. Med. Virol. 85: 944–952, 2013. © 2013 Wiley Periodicals, Inc.     

Effects of a hemagglutinin D222G substitution on the pathogenicity of 2009 influenza A (H1N1) virus in mice

The surface glycoprotein hemagglutinin (HA) of influenza virus initiates the infection process by binding to sialic acid receptors on upper respiratory cells in the host. In contrast to avian influenza viruses, which bind to sialic acids connected by an α2-3 linkage to the penultimate galactose, human influenza viruses prefer sialic acids with an α2-6 linkage. Recently, there have been multiple cases of severe human infections associated with an HA D222G mutant influenza virus. In this study, we have investigated the pathogenic effects of the HA D222G substitution in a 2009 pandemic H1N1 virus in mice. Compared with the A/Korea/01/2009 (K/09) virus, the HA D222G mutant showed reduced growth in cells and reduced binding avidity to human and turkey red blood cells. In a BALB/c mouse infection model, infection with the HA D222G mutant virus resulted in less body weight loss when compared to the parental K/09 virus. Altogether, our data suggest that the HA D222G substitution in the K/09 virus might be deleterious to viral fitness.     

2011-2017年河北省甲型H1N1流感流行特征分析

目的掌握河北省甲型H1N1流感的流行特征,为流感防控提供科学依据.方法通过中国流感监测信息系统收集河北省2011年4月至2017年3月流感及流感样病例(influenza-likeillness,ILI)监测数据进行统计分析.结果共检测ILI标本77 008份,甲型H1N1流感病毒核酸阳性2 699份,阳性率3.50％.对2 699例甲型H1N1流感病例进一步分析显示:全省11个地市均有该病例检出,男女比例为1.09:1,各年龄组均可发病,检出率最高的是25～59岁组,最低0～4岁组.2011年11月至2017年3月共出现4次流行,具有明显的季节性,且呈单峰性.各年度均有甲型H1N1流感病例检出,甲型H1N1流感分别是2012-2013、2013-2014和2016-2017年度的优势病原.结论河北省甲型N1N1流感流行具有明显的季节性,冬春季流行,近年来感染以5～14岁年龄组为主.     

Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets

The hemagglutinin of the 2009 pandemic H1N1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human H1N1 viruses. We compared the A/California/7/2009 (CA/7/09) virus recommended by the WHO as the reference virus for vaccine development, with two classical swine influenza viruses A/swine/Iowa/31 (sw/IA/31) and A/New Jersey/8/1976 (NJ/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. Primary infection with 2009 pandemic or NJ/76 viruses elicited antibodies against the CA/7/09 virus and provided complete protection from challenge with this virus in ferrets; the response in mice was variable and conferred partial protection. Although ferrets infected with sw/IA/31 virus developed low titers of cross-neutralizing antibody, they were protected from pulmonary replication of the CA/7/09 virus. The data suggest that prior exposure to antigenically related H1N1 viruses of swine-origin provide some protective immunity against the 2009 pandemic H1N1 virus.     

High doses of recombinant mannan‐binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC‐SIGN

The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human health. Low doses of mannan‐binding lectin (MBL) (<1 μg/mL) were shown not to protect against influenza A(H1N1)pdm09 infection. However, the effect of high doses of MBL has not been investigated. Dendritic cell‐specific intercellular adhesion molecule‐3 grabbing non‐integrin (DC‐SIGN) has been proposed as an alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined the expression of DC‐SIGN on DCs as well as on acute monocytic leukemia cell line, THP‐1. High doses of recombinant or human MBL inhibited binding of influenza A(H1N1)pdm09 to both these cell types in the presence of complement derived from bovine serum. Further, anti‐DC‐SIGN monoclonal antibody inhibited binding of influenza A(H1N1)pdm09 to both DC‐SIGN‐expressing DCs and THP‐1 cells. This study demonstrates that high doses of MBL can inhibit binding of influenza A(H1N1)pdm09 virus to DC‐SIGN‐expressing cells in the presence of complement. Our results suggest that DC‐SIGN may be an alternative receptor for influenza A(H1N1)pdm09 virus.     

Validation of commercial real-time RT-PCR kits for detection of influenza A viruses in porcine samples and differentiation of pandemic (H1N1) 2009 virus in pigs

Swine influenza, apart from its importance in animal health, may also be of public health significance. Although the first human infections with the multi-reassortant H1N1 virus (pH1N1/09) responsible for the 2009 pandemic were not related to pig exposure, this virus was shown to be related genetically to swine influenza viruses (SIV) and easily transmissible to pigs. In addition to direct animal health concerns, transmission and possible adaptation of the pH1N1/09 virus in pigs may have serious consequences on the risk of human infection by increasing the reservoir of this virus and the risk of possible emergence of new reassortant viruses with increased virulence for pigs and/or humans. Sensitive tools to monitor and detect rapidly such an infection are therefore mandatory. In this study, five commercial real-time RT-PCR assays developed by manufacturers LSI and Adiagène were assessed and validated, (i) for rapid detection of influenza A viruses, including pH1N1/09, in pig and (ii) for the differentiation of pH1N1/09 in that species. Two kits target the influenza A virus M gene, two others amplify the pH1N1/09 virus H1 gene and one kit targets the pH1N1/09 virus N1 gene. All five kits are ready-to-use, one-step duplex RT-PCR and contain an internal positive control (IPC), appropriate for porcine biological samples, for assessing RNA extraction efficiency and the presence of PCR inhibitors. They have been used successfully by veterinary laboratories and shown to be powerful tools for the diagnosis and epidemiological surveillance of influenza virus infections in pigs.     

Detection of haemagglutinin D222 polymorphisms in influenza A(H1N1)pdm09-infected patients by ultra-deep pyrosequencing

This study was aimed at establishing the genetic heterogeneity of influenza virus haemagglutinin (HA) gene quasi-species and the polymorphisms at codon 222, by application of ultra-deep pyrosequencing (UDPS) to respiratory samples from patients hospitalized for influenza A(H1N1)pdm09 infection, presenting with severe or moderate–mild disease. HA diversity was significantly higher in samples collected from patients with severe manifestations than in those from patients with moderate–mild manifestations (p 0.02). D222 polymorphism was detected in 40.7% of patients by UDPS, and in only 7.1% by Sanger sequencing. D222E, D222G, D222N and D222A were observed in 37.0%, 11.1%, 7.4% and 3.7% of patients, respectively; 10.7% of samples harboured more than two variants. The relative frequency of each single variant showed a wide range of intrapatient variation. D222G/N/A were detected, as either minor or predominant variants, only in severe cases, whereas D222E was equally represented in severe and moderate–mild infections. Other amino acid variants were observed at different positions within the analysed HA fragment. Consistent with higher heterogeneity, non-D222 variants were more frequently detected in severe cases than in moderate–mild cases. In addition, seven non-D222 mutations carried by minority variants, not previously described, were observed.     

Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health

Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens.     

Isolation and characterization of two H5N1 influenza viruses from swine in Jiangsu Province of China

Pigs are susceptible to infection with both human and avian influenza A viruses and are considered intermediate hosts that facilitate virus reassortment. Although H5N1 virus has spread to a wide range of avian and mammalian species, data about swine H5N1 isolates are scarce. To determine whether Asian H5N1 influenza viruses had been transmitted to pigs, a total of 1,107 nasal swab samples from healthy swine were collected from 2008 to 2009 in Jiangsu province of eastern China. In this survey, two H5N1 viruses A/swine/Jiangsu/1/2008 (JS/08) and A/swine/Jiangsu/2/2009 (JS/09) were isolated and identified. Phylogenetic analysis showed that JS/08 and JS/09 belonged to clade 7 and clade 2.3.4, respectively, and shared over 99.0 % sequence identity with poultry H5N1 isolates of the same clade in China. Receptor specificity analysis also showed that both of the swine H5N1 isolates bound preferentially to avian-type receptors. However, experiments in mammals indicated that JS/09 was moderately pathogenic to mice without prior adaption, whereas JS/08 had limited ability to replicate. Our findings suggest that pigs are naturally infected with avian H5N1 virus and highlight the potential threat to public health due to adaption or reassortment of H5N1 virus in this species.     

Pathogenic aspects of influenza during the epidemics caused by A/H1N1v virus in 2009-2010 according autopsy data

The paper is based upon the results of clinic-pathological and virological correlations in 29 lethal cases of influenza in Saint-Petersburg and Leningrad region during the epidemics 2009/2010. Immunohistochemical analysis of lungs, heart and brain using monoclonal sera to HA and HP proteins of influenza virus, virological and morphological analysis of experimental influenza in mice infected by A/WSN/33 (HIN1) and A/California/07/09 (H1N1) viruses had been carried out. In the majority of investigated strains was proved the amino acid mutation with replacement D222G. The replication of virus was demonstrated at the late stages of diseases, but the desquamation of respiratory epithelium and cytoproliferative weren't found out. Besides the "influenza cells", previously described by A. V Zinserling the cells with enlarge light nuclei were observed. Patients with influenza died from respiratory distress syndrome with minimal bacterial infection. We've established that H1N1 virus not only damages the cells of respiratory epithelium and alveolar macrophages but it can injure endothelium of different organs and neuroglia. The questions which have to be discussed are listed.     

Heparin-binding protein (HBP) in critically ill patients with influenza A (H1N1) infection

Heparin-binding protein (HBP) is an inducer of vascular endothelial leakage in severe infections. Fluid accumulation into alveoli is a general finding in acute respiratory distress syndrome (ARDS). Severe acute respiratory failure with ARDS is a complication of influenza A(H1N1) infection. Accordingly, we studied the HBP levels in critically ill patients with infection of influenza A(H1N1).Critically ill patients in four intensive care units (ICUs) with polymerase chain reaction (PCR) confirmed infection of influenza A(H1N1) were prospectively evaluated. We collected clinical data and blood samples at ICU admission and on day 2. Twenty-nine patients participated in the study. Compared with normal plasma levels, the HBP concentrations were highly elevated at baseline and at day 2: 98 ng/mL (62–183 ng/mL) and 93 ng/mL (62–271 ng/mL) (p 0.876), respectively. HBP concentrations were correlated with the lowest ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PF ratio) during the ICU stay (rho = ?0.321, p <0.05). In patients with and without invasive mechanical ventilation, the baseline HBP levels were 152 ng/mL (72–237 ng/mL) and 83 ng/mL (58–108 ng/mL) (p 0.088), respectively. The respective values at day 2 were 223 ng/mL (89–415 ng/mL) and 81 ng/mL (55–97 ng/mL) (p <0.05). The patients with septic shock/severe sepsis (compared with those without) did not have statistically significant differences in HBP concentrations at baseline or day 2. HBP concentrations are markedly elevated in all critically ill patients with influenza A(H1N1) infection. The increase in HBP concentrations seems to be associated with more pronounced respiratory dysfunction.