IntroductionHuman host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1.MethodsWe profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene.ResultsIncreased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients.ConclusionsWhile infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Seasonal influenza is a cause of hospitalization, especially in people with underlying disease or extreme age, and its severity may differ depending on the types and subtypes of circulating viruses. We investigated the factors associated with ICU admission or death in hospitalized patients with severe laboratory-confirmed influenza according to the viral type and subtype. An observational epidemiological study was carried out in patients aged ≥18 years from 12 Catalan hospitals between 2010 and 2016. For each reported case we collected demographic, virological and clinical characteristics. A mixed-effects logistic regression model was used to estimate crude and adjusted ORs. 1726 hospitalized patients were included: 595 (34.5%) were admitted to the ICU and 224 (13.0%) died. Lower ICU admission was associated with age ≥75 years in all influenza types and subtypes and with age 65–74 years for type A. In contrast, the 65–74 and ≥75 years age groups were associated with an increased risk of death in all types and subtypes, especially for type B (aOR 27.42, 95% CI: 4.95–151.93 and 15.96; 95% CI: 3.01–84.68). The comorbidity most closely associated with severe outcomes was immune deficiency, which was associated with death for type B (aOR 9.02, 95% CI: 3.05–26.69) and subtype A(H1N1)pdm09 (aOR 3.16, 95% CI: 1.77–5.66). Older age was a differential factor for ICU admission and death: it was associated with lower ICU admission but a risk factor for death. The comorbidity with the closest association with death was immune deficiency, mainly in influenza type B patients.