Severe 2009 A/H1N1v influenza in pregnant women in Spain.

OBJECTIVES: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. DESIGN AND PATIENTS: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. MAIN RESULTS: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. CONCLUSIONS: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Host adaptive immunity deficiency in severe pandemic influenza.

INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.