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Humans are repeatedly exposed to variants of influenza virus throughout their lifetime. As a result, preexisting influenza-specific memory B cells can dominate the response after infection or vaccination. Memory B cells recalled by adulthood exposure are largely reactive to conserved viral epitopes present in childhood strains, posing unclear consequences on the ability of B cells to adapt to and neutralize newly emerged strains. We sought to investigate the impact of preexisting immunity on generation of protective antibody responses to conserved viral epitopes upon influenza virus infection and vaccination in humans. We accomplished this by characterizing monoclonal antibodies (mAbs) from plasmablasts, which are predominantly derived from preexisting memory B cells. We found that, whereas some influenza infection-induced mAbs bound conserved and neutralizing epitopes on the hemagglutinin (HA) stalk domain or neuraminidase, most of the mAbs elicited by infection targeted non-neutralizing epitopes on nucleoprotein and other unknown antigens. Furthermore, most infection-induced mAbs had equal or stronger affinity to childhood strains, indicating recall of memory B cells from childhood exposures. Vaccination-induced mAbs were similarly induced from past exposures and exhibited substantial breadth of viral binding, although, in contrast to infection-induced mAbs, they targeted neutralizing HA head epitopes. Last, cocktails of infection-induced mAbs displayed reduced protective ability in mice compared to vaccination-induced mAbs. These findings reveal that both preexisting immunity and exposure type shape protective antibody responses to conserved influenza virus epitopes in humans. Natural infection largely recalls cross-reactive memory B cells against non-neutralizing epitopes, whereas vaccination harnesses preexisting immunity to target protective HA epitopes., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In France, the surveillance of hospitalized cases of pandemic influenza was implemented in July 2009 and restricted to intensive-care unit (ICU) patients in November. We described the characteristics of the 1065 adult patients admitted to ICUs and analysed risk factors for severe outcome (mechanical ventilation or death). Eighty-seven percent of cases were aged 15-64 years. The case-fatality ratio was 20%. The risk for severe outcome increased with age and obesity while this association was negative for chronic respiratory disease. Late antiviral therapy was associated with a severe outcome in ICU patients with risk factors (adjusted OR 2·0, 95% CI 1·4-3·0). This study confirms the considerable contribution of young adults to A(H1N1) 2009 mortality. It shows the role of obesity as an independent risk factor for severe disease, and of early antiviral therapy as a protective factor, at least in patients with risk factors.

From 1 July 2009 to 15 November 2009, 244 patients with 2009 pandemic influenza A(H1N1) were admitted to intensive care unit (ICU) and were compared with 514 cases hospitalised in medical wards in France until 2 November 2009. Detailed case-based epidemiological information and outcomes were gathered for all hospitalised cases. Infants and pregnant women are overrepresented among cases admitted to ICU with seven per cent for both groups respectively, and twenty per cent of ICU cases did not belong to a risk group. Chronic respiratory disease was the most common risk factor among cases but obesity (body mass index >or= 30 Kg/m(2)), chronic cardiac disease and immunosuppression were risk factors associated with severe illness after adjustment for age and for other co-morbidities.

Several countries plan to introduce non-contact infrared thermometers (NCIT) at international airports in order to detect febrile passengers, thus to delay the introduction of a novel influenza strain. We reviewed the existing studies on fever screening by NCIT to estimate their efficacy under the hypothesis of pandemic influenza. Three Severe Acute Respiratory Syndrome (SARS) or dengue fever interventions in airports were excluded because of insufficient information. Six fever screening studies in other gathering areas, mainly hospitals, were included (N= 176 to 72,327 persons; fever prevalence= 1.2% to 16.9%). Sensitivity varied from 4.0% to 89.6%, specificity from 75.4% to 99.6%, positive predictive value (PPV) from 0.9% to 76.0% and negative predictive value (NPV) from 86.1% to 99.7%. When we fixed fever prevalence at 1% in all studies to allow comparisons, the derived PPV varied from 3.5% to 65.4% and NPV was >or=99%. The low PPV suggests limited efficacy of NCIT to detect symptomatic passengers at the early stages of a pandemic influenza, when fever prevalence among passengers would be =or<1%. External factors can also impair the screening strategy: passengers can hide their symptoms or cross borders before symptoms occur. These limits should be considered when setting up border control measures to delay the pandemic progression.