Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain

The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive‐care unit (ICU) admission or in‐hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co‐infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05–5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41–6.09), morbid obesity (OR, 6.7; 95% CI, 2.25–20.19), concomitant and secondary bacterial co‐infection (OR, 2.78; 95% CI, 1.11–7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16–0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co‐infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.     

Clinical evaluation of rapid point-of-care testing for detection of novel influenza A (H1N1) virus in a population-based study in Spain

Limited information exists on the performance of antigen-based rapid influenza diagnostic tests (RIDT) in diagnosing the novel influenza A pandemic (H1N1) 2009 virus. Large studies evaluating these tests in consecutive patients with a broad clinical spectrum of influenza-like illnesses are needed. We assessed the ClearView® Exact Influenza A & B test (Inverness Medical, Cologne, Germany) in comparison with real-time (r)RT-PCR for detection of the novel influenza A (H1N1) in a population-based prospective study of 1016 adults and children with suspected influenza in Spain. Three hundred and one (29.6%) patients had a positive sample with the rRT-PCR assay for influenza A and B viruses, with 297 (29.2%) confirmed cases of the novel influenza A pandemic (H1N1) 2009 virus. Fifty (16.8%) patients with confirmed A (H1N1) 2009 virus were admitted to hospital, with six of them to the intensive care unit. In comparison with rRT-PCR, the ClearView® Exact Influenza A & B test had a sensitivity of 19% (95% CI 14–23), a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 75% (95% CI 72–78). The sensitivity of the test remained low across all demographic and clinical strata. Although a positive RIDT performed well in predicting PCR-confirmed infection with pandemic H1N1 virus, the sensitivity was very low and a negative test result was a poor predictor of the absence of infection.     

High Non‐Specific T Lymphocyte Response to the Adjuvanted H1N1 Vaccine in Comparison with the H1N1/H3N2/B‐Brisbane Vaccine without Adjuvant

Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non‐adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non‐specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1‐specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene‐based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non‐adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B‐Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1‐induced immunogenicity was good for both vaccines. Our results suggest a pronounced non‐specific T cell response after AS03‐adjuvanted 2009 H1N1 vaccination.     

H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination

A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix^® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu‐specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor‐binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.     

2009甲型H1N1流感大流行期间北京儿童的流感监测

目的 了解2009年甲型H1N1流感大流行期间北京地区儿童中流感流行的情况.方法 采用WHO推荐的实时荧光定量RT-PCR和国家流感中心推荐的分型方法,对2009年甲型H1N1流感大流行期间因流感样症状来首都儿科研究所附属儿童医院就诊患儿的咽拭子标本进行流感病毒核酸检测.结果 2009年6月1日至2010年2月28日期间共检测了4363份咽拭子标本,其中623例为甲型H1N1阳性,阳性率为14.3%,657例为其他甲型流感病毒阳性(15.1%),所有甲型流感病毒的总阳性率为29.3%.623例中有23例为危重症病例(占阳性患者的3.7%),其中5例死亡.618例信息完整的甲型H1N1病例中,患儿年龄为14天～16岁,性别比例为男比女为1.3:1.1～3岁儿童占25.2%,3～6岁学龄前儿童和6～12岁学龄儿童所占比例相近,各约占30%.在监测期间,仅呈现了一个甲型H1N1的流行波.2009年11月达到最高峰,随后减弱,2010年2月快速下降至2.7%.对监测期间每周20～30份临床标本同时进行季节性流感的监测显示,季节性H3N2、甲型H1N1和乙型流感交替流行.呼吸道合胞病毒(RSV)在甲型H1N1流行趋势减缓后逐渐流行成为流行优势株.结论 2009年6月至2010年2月北京地区儿童中出现甲型H1N1的流行,主要累及学龄前和学龄儿童.季节性流感和RSV与甲型H1N1交替流行.     

Sero‐immunity and serologic response to pandemic influenza A (H1N1) 2009 virus in Hong Kong

To study the serologic response to the new pandemic influenza A (H1N1) 2009 virus in Hong Kong, the level of immunity was measured before and after the occurrence of the outbreak, and the titer of antibody to the pandemic influenza A (H1N1) 2009 virus in serum samples of laboratory confirmed cases. The presence of pre‐outbreak pandemic influenza A (H1N1) 2009 virus antibodies in 37% of individuals older than >65 years suggested previous exposures to heterologous virus strains may have elicited cross‐reacting antibody. Following large outbreaks of pandemic influenza A 2009 virus that peaked in September 2009, there is a change in immunity level in various age groups consistent with the attack rates among population in Hong Kong. Among individuals with mild clinical presentation, the antibody response to pandemic influenza A (H1N1) 2009 virus was stronger in those individuals aged ≤24 years but took more time to reach a titer of 40 when compared with those aged >24 years; however, the antibody level declined slower among individuals aged ≤24 years. Regardless of age, the antibody response rose rapidly and reached much higher titer among individuals with severe clinical presentation. Further study is required to collect additional data on antibody persistence and determine how much protection is conferred by previous exposure to seasonal influenza A (H1N1) viruses. J. Med. Virol. 82:1809–1815, 2010. © 2010 Wiley‐Liss, Inc.     

Prolonged viral shedding in pandemic influenza A(H1N1): clinical significance and viral load analysis in hospitalized patients

The clinical significance of prolonged viral shedding (PVS) and viral load (VL) dynamics has not been sufficiently assessed in hospitalized patients with pandemic 2009 influenza A(H1N1). We performed a prospective study of adults with confirmed influenza A(H1N1) virus infection admitted to our hospital from 20 September 2009 to 31 December 2009. Consecutive nasopharyngeal swabs were collected every 2 days during the first week after diagnosis, and then every week or until viral detection was negative. Relative VL was measured on the basis of haemagglutinin and RNaseP gene analysis. PVS was defined as positive detection of influenza A(H1N1) virus by real-time RT-PCR at day 7 after diagnosis. We studied 64 patients: 16 (25%) presented PVS. The factors associated with PVS were admission to the intensive-care unit (69% vs. 33%, p 0.02), purulent expectoration (75% vs. 44%, p 0.04), higher dosage of oseltamivir (62.5% vs. 27%, p 0.016), corticosteroid treatment (50% vs. 21%, p 0.05), mechanical ventilation (MV) (50% vs. 12.5%, p 0.004), and longer stay (34 vs. 7 median days, p 0.003). Multivariate analysis revealed the factors independently associated with PVS to be immunosuppression (OR 5.15; 95% CI 1.2–22.2; p 0.03) and the need for MV (OR 11.7; 95% CI 2.5–54.4; p 0.002). VL at diagnosis correlated negatively with age and septic shock. VL dynamics of patients with acute respiratory distress syndrome and/or mortality were very different from those of other patients. PVS was detected in 25% of hospitalized patients with pandemic 2009 influenza A(H1N1) and was strongly associated with immunosuppression and the need for MV. Diagnostic VL and viral clearance varied with the clinical course.     

Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay

A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10^{3.0 ± 0.4} tissue culture infective dose (TCID)₅₀/mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8–96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9–100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9–100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.     

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.     

Duration of viral shedding in patients admitted to hospital with pandemic influenza A/H1N1 2009 infection

Little is known about the kinetics of viral shedding of pandemic influenza A/H1N1 2009 virus. Influenza RNA, as a surrogate for viral clearance, was therefore measured on days 1, 5, 7, and 10 or more in patients admitted to hospital with pandemic influenza A/H1N1 2009 infection. A total of 72 patients who were admitted to hospital with confirmed pandemic influenza A/H1N1 2009 at a tertiary care hospital, Seoul, South Korea, between 1 September and 11 November 2009 were evaluated. The median duration of viral shedding, as assessed by RT-PCR, was 9 days, as determined by the Kaplan-Meier method. Patients who were positive by RT-PCR at their last assay, but who were discharged before the next RT-PCR test due to symptom improvement, were censored from the analysis. If such patients were included, with the assumption that they had negative viral status at discharge, the median duration of viral shedding was 5 days (interquartile range, 2-8 days). These calculations thus suggest that the true median duration of viral shedding is between 5 and 9 days. Univariate analysis showed that delayed administration of antiviral therapy and comorbidity were associated with slower viral clearance. Multivariate analysis showed that oseltamivir started after the first day of symptoms (OR 2.7, 95% CI 1.2-5.7) was associated independently with slower viral clearance. These findings indicate that, in about 50% of patients admitted to hospital with pandemic influenza A/H1N1 2009, virus can be positive as tested by RT-PCR on the eighth day after developing symptoms of influenza. The present findings also indicate that starting antiviral therapy within 24 hr of the onset of symptoms is associated with more rapid viral clearance.     

Novel H1N1-associated rhabdomyolysis leading to acute renal failure

The WHO recently declared that the novel influenza H1N1 virus was responsible for the 2009 flu pandemic. As the virus continues to spread globally and affect more individuals, more complications of infection with this virus are being recognized. To our knowledge, we report the first case of H1N1-induced rhabdomyolysis leading to acute renal failure in an adult. This case highlights the importance of recognizing a significant extrapulmonary complication of H1N1 infection.     

A prediction rule to identify severe cases among adult patients hospitalized with pandemic influenza A (H1N1) 2009

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO(2)/FiO(2) ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.     

Genetic diversity of HA1 domain of hemagglutinin gene of pandemic influenza H1N1pdm09 viruses in New Delhi, India

Genetic analysis of pandemic 2009 influenza A (H1N1; H1N1pdm09) virus was undertaken to understand virus evolution during 2009 and 2010 in India. Surveillance of influenza viruses from July 2009 to December 2010 revealed major peaks of circulating H1N1pdm09 viruses in August–September and December–January 2009 and then in August–September 2010. To understand the diversity of the H1N1pdm09 virus, selected specimens (n = 23) from 2009 or 2010 were characterized by nucleotide sequence determination of the HA1 subunit of the HA gene. Phylogenetic analysis revealed that 22 clustered with clade 7 viruses characterized by S203T mutations, whereas one virus from 2010 fell within clade 6. None of the viruses from either 2009 or 2010 formed a monophyletic group, suggesting a continuum of independent introduction of circulating viral strains. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor‐binding domains. Importantly, we observed mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 3 of 13 viruses analyzed from 2010, while none of the 2009 viruses carried these mutations. Whether antibody‐mediated pressure is imposing such changes remains to be determined. Continued genetic surveillance is warranted to monitor pathogenicity as the virus evolves to acquire new features. J. Med. Virol. 84:386–393, 2012. © 2011 Wiley Periodicals, Inc.     

Influenza virus infections from 0 to 2 years of age: A birth cohort study

Background/purposeInfluenza vaccine has been recommended in Finland since 2007 for all children of 6–35 months of age and in 2009 for those ≥6 months against pandemic influenza. We investigated the incidence of influenza and vaccine effectiveness in a birth cohort of children in 2008–2011.MethodsWe followed 923 children from birth to 2 years of age for respiratory tract infections. A nasal swab sample for PCR for influenza A and B viruses was taken at the onset of acute respiratory infections. Samples were collected either at the study clinic or at home by parents. Vaccination data was retrieved from the health registries.ResultsVaccination coverage of children aged 6–23 months was 22–47% against seasonal influenza and 80% against the A(H1N1)pdm09 virus in the pandemic season 2009–2010. During 3 influenza seasons, 1607 nasal swab samples were collected. Influenza was confirmed in 56 (6.1%) of 923 children (16 A(H1N1), 14 A(H3N2), and 26 B viruses). The incidence of influenza was 5.1% in 2008–2009, 2.7% in 2009–2010, and 5.0% in 2010–2011. Effectiveness of the adjuvanted vaccine against the pandemic influenza A(H1N1)pdm09 was 97% (95% confidence interval, 76–100%). Three children with influenza were hospitalized.ConclusionThe yearly incidence of seasonal influenza was 5% in this cohort of very young children with variable influenza vaccine coverage. Adjuvanted vaccine against the pandemic influenza was highly effective. Both seasonal and pandemic influenza cases were mostly non-severe.     

Oseltamivir-resistant 2009–2010 pandemic influenza A (H1N1) in an immunocompromised patient

Although neuraminidase inhibitors are active against most 2009–2010 pandemic influenza A (H1N1) swine-origin strains, sporadic cases of oseltamivir resistance have been described. Since April 2009, 54 cases of oseltamivir-resistant H1N1 swine-origin have been reported in the USA (http://www.cdc.gov/flu/weekly/; accessed 1 February 2010). Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.     

甲型H1N1流感患者外周血白细胞和淋巴细胞亚群变化分析

目的 探讨甲型H1N1流感患者白细胞和淋巴细胞亚群的变化特点,为甲型H1N1流感的诊断、治疗和预后判断提供实验室依据.方法 采用全血细胞分析和流式细胞分析法分别检测59例甲型H1N1流感患者急性期和恢复期的外周血白细胞及淋巴细胞亚群,与43名健康人和24例普通甲型流感患者比较.结果 甲型H1N1流感轻症患者白细胞总数在急性期显著下降,重症患者白细胞总数下降不显著,而中性粒细胞显著升高;与普通甲型流感相似,所有H1N1流感患者淋巴细胞总数、CD3、CD4、CD8百分比和绝对值在急性期大幅度下降,恢复期迅速回升;而重症患者NK和NKT细胞绝对值在急性期下降幅度超过20%.结论 甲型H1N1流感患者白细胞和淋巴细胞亚群变化与普通甲流相似;急性期NK、NKT细胞绝对值的大幅降低可以提示病情重症化倾向.     

Pandemic influenza A (H1N1) 2009 vaccine: an update

The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.     

Seasonal H1N1 2007 influenza virus infection is associated with elevated pre‐exposure antibody titers to the 2009 pandemic influenza A (H1N1) virus

The new influenza strain detected in humans in April 2009 has caused the first influenza pandemic of the 21st century. A cross‐reactive antibody response, in which antibodies against seasonal H1N1 viruses neutralized the 2009 pandemic influenza A (H1N1) virus (2009 pH1N1), was detected among individuals aged >60 years. However, factors other than age associated with such a cross‐reactive antibody response are poorly documented. Our objective was to examine factors potentially associated with elevated pre‐exposure viro‐neutralization and hemagglutination‐inhibition antibody titers against the 2009 pH1N1. We also studied factors associated with antibody titers against the 2007 seasonal H1N1 virus. One hundred subjects participating in an influenza cohort were selected. Sera collected in 2008 were analysed using hemagglutination inhibition and viro‐neutralization assays for the 2009 pH1N1 virus and the 2007 seasonal H1N1 virus. Viro‐neutralization results were explored using a linear mixed‐effect model and hemagglutination‐inhibition results using linear‐regression models for interval‐censored data. Elevated antibody titers against 2009 pH1N1 were associated with seasonal 2007 H1N1 infection (viro‐neutralization, p 0.006; hemagglutination‐inhibition, p 0.018). Elevated antibody titers were also associated with age in the viro‐neutralization assay (p <0.0001). Seasonal 2007 H1N1 infection is an independent predictor of elevated pre‐exposure antibody titers against 2009 pH1N1 and may have contributed to lowering the burden of the 2009 pH1N1 pandemic.