Long-term Outcomes of Pandemic 2009 Influenza A(H1N1)-Associated Severe ARDS

Luyt, Charles‐Édouard; Combes, Alain; Becquemin, M.H.; Beigelman-Aubry, Cathérine; Hatem, Stéphane N.; Brun, Anne-Laure; Zraik, Nizar; Carrat, Fabrice; Greniér, Philippe; Richard, Jean-Christophe M.; Mercat, Alain; Brochard, Laurent; Brun‐Buisson, Christian; Chastre, Jean

doi:10.1378/chest.11-2196

Cited by 209 publications

(208 citation statements)

References 34 publications

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“…Histological analyses performed until 21 days following IAV infection revealed that pneumonia was established even after complete recovery of body weight and viral clearance. In fact, the few long-term follow-up studies with small cohorts of patients that survived acute H1N1 infection have revealed that structural abnormalities in the lung parenchyma can last up to a year after respiratory disease (51,52). When coinfections were performed on day 14 following IAV infection, we indeed still observed impaired clearance of S. pneumoniae.…”

Section: Discussionmentioning

confidence: 68%

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

et al. 2016

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e Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of S. pneumoniae and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary S. pneumoniae infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different S. pneumoniae strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal S. pneumoniae infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and S. pneumoniae is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks. Infection with secondary bacterial pathogens is attributed to be the major cause of excessive mortality during influenza A virus (IAV) outbreaks. This lethal synergism has been recognized as early as during the 1918-1919 IAV pandemic with an estimated global death toll of 50 to 100 million (1, 2). Retrospective studies disclosed that 71% of the fatal cases during this pandemic were positive for Streptococcus pneumoniae (also called pneumococcus), providing the first epidemiological evidence for viral-bacterial coinfections (2). A clear predisposition to bacterial disease was also evident in all of the succeeding influenza pandemics, including the more recent 2009 H1N1 outbreak, which had a 10 to 55% higher incidence of hospitalizations and mortality due to bacterial pneumonia (3). Pneumococcal colonization is transient and asymptomatic in immunocompetent individuals and most commonly occurs in early childhood (4). At the same time, however, pneumococci are able to cause a variety of diseases ranging from mild sinusitis and otitis media to more-severe infections like sepsis and meningitis. Even though the introduction of the polyvalent pneumococcal conjugate vaccines...

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Section: Discussionmentioning

confidence: 68%

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

et al. 2016

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“…During this period, severely ill patients were diagnosed with acute respiratory distress syndrome (ARDS) (defined by the American-European Consensus Conference on ARDS) (35) caused by A(H1N1)pdm09 virus infection. All were recruited from the Réseau Européen de Ventilation Artificielle (REVA) registry (36). Table 1 summarizes the characteristics of all 3 groups of subjects.…”

Section: Methodsmentioning

confidence: 99%

Characterization of pandemic influenza immune memory signature after vaccination or infection

Bonduelle¹,

Carrat²,

Luyt³

et al. 2014

J. Clin. Invest.

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The magnitude, quality, and maintenance of immunological memory after infection or vaccination must be considered for future design of effective influenza vaccines. In 2009, the influenza pandemic produced disease that ranged from mild to severe, even fatal, illness in infected healthy adults and led to vaccination of a portion of the population with the adjuvanted, inactivated influenza A(H1N1)pdm09 vaccine. Here, we have proposed a multiparameter quantitative and qualitative approach to comparing adaptive immune memory to influenza 1 year after mild or severe infection or vaccination. One year after antigen encounter, severely ill subjects maintained high levels of humoral and polyfunctional effector/memory CD4 + T cells responses, while mildly ill and vaccinated subjects retained strong cellular immunity, as indicated by high levels of mucosal homing and degranulation markers on IFN-γ + antigen-specific T cells. A principal component analysis distinguished 3 distinct clusters of individuals. The first group comprised vaccinated and mildly ill subjects, while clusters 2 and 3 included mainly infected individuals. Each cluster had immune memory profiles that differed in magnitude and quality. These data provide evidence that there are substantial similarities between the antiinfluenza response that mildly ill and vaccinated individuals develop and that this immune memory signature is different from that seen in severely ill individuals.

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“…49,50 However, the severity of ARDS, defined as requiring extracorporeal lung assist, does not seem to influence the psychological impairment at 1 y in terms of symptoms of anxiety, depression, and risk of posttraumatic stress disorder. 27 Most of the literature concludes that physiopathological alterations related to the critical illness (hypoxemia, activation of the hypothalamicpituitary axis, elevated cytokines, organ dysfunction) and medications (epinephrine or norepinephrine, sedatives) contribute all together to the long-term psychological disorders. Little is also known about the pathophysiology of the neurocognitive impairment after ARDS.…”

Section: Neuropsychological Disabilitymentioning

confidence: 99%

What's Next After ARDS: Long-Term Outcomes

et al. 2016

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SummaryARDS is a life-threatening organ failure due to several pulmonary and extrapulmonary injuries with an incidence between 5 and 60 cases/100,000 persons/y. Patients with ARDS have non-cardiogenic pulmonary edema and dyspnea often requiring invasive mechanical ventilation and intensive care admission. Although the short-term mortality rate has significantly decreased in the last decade, mainly due to the widespread application of lung-protective ventilation and better general support, long-term outcomes are still unsatisfactory. Besides simply evaluating the outcome at hospital discharge, several recent studies have assessed the health-related quality of life, neuropsychological disability, radiological findings, and pulmonary dysfunction up to 5 y. This paper reviews the literature regarding the long-term outcomes in patients with ARDS. Key words: ARDS; long-term outcomes; health-related quality of life; neuropsychological disability; pulmonary function; lung imaging. [Respir Care 2016;61(5):689 -699.

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Long-term Outcomes of Pandemic 2009 Influenza A(H1N1)-Associated Severe ARDS

Cited by 209 publications

References 34 publications

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

Characterization of pandemic influenza immune memory signature after vaccination or infection

What's Next After ARDS: Long-Term Outcomes

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