Characteristics and outcome of ill critical patients with influenza A infection

Introduction To describe all patients admitted to Tunisian intensive care unit with a diagnosis of influenza A/H1N1 virus infection after the 2009 influenza pandemic and to analyse their characteristics, predictors of complications and outcome. Methods All patients with influenza > 18-years-old hospitalized to the ICU department of Tunisian University hospital of Sousse, between December 1, 2009 and March 31, 2016, with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included, were included. Results 40 cases were admitted to intensive care units. During the reporting period, 22 deaths in intensive care units (55%) were reported, the median age was 53 years (IQR 37-61), 24 (61%) were male, The median scores SAPS II and SOFA were respectively 29 (IQR 23-36) and 6 (IQR 3-10), 27% had chronic obstructive pulmonary disease (COPD), 33.3% diabetic and no patients were vaccinated against influenza A. The cause of admission was in 72.5% of the cases was hypoxemic pneumonae. By using a logistic regression, we found after adjustment to age, that acute respiratory distress syndrome (ARDS) (OR = 27; 95%CI: 3.62-203.78) was the only factor significantly associated with severe outcomes of the cases. Conclusion Patients in the first post pandemic season were significantly older and more frequently had underlying medical conditions. Multivariate analysis showed that older male patients with chronic lung disease were at increased risk for a severe clinical outcome.


Introduction
Influenza pandemics have been associated with increased illness and death. Each pandemic is different, and areas of uncertainty always exist when an influenza virus emerges and becomes pandemic. In April 2009, the novel influenza A (H1N1) pdm09 virus emerged in Mexico and then spread rapidly throughout the world [1]. Influenza is generally a self-limiting infection with systemic and respiratory symptoms that usually resolve after 3-6 days. Most persons infected with the 2009 influenza A (H1N1) pdm09 virus experienced uncomplicated illness with full recovery within 1 week, even without medical treatment; severe progressive disease developed in only a small subset of patients [2]. Primary viral pneumonia was the most common finding in severe cases, but secondary bacterial infections played a role in ≈30% of fatal cases [3]. Hospitalized patients were often affected by other medical conditions, such as diabetes and cardiovascular, neurologic and pulmonary diseases [4]. Advances in therapy for malignancies, autoimmune disorders and end-stage organ diseases have led to improved survival, but also to an increase in the number of immunosuppressed patients. These patients are particularly at risk for opportunistic and community-acquired infections, such as respiratory virus infections, resulting in considerable illness and death [5]. Although patients hospitalized with pandemic influenza A (H1N1) pdm09 infection had substantial severe illness, the overall number of deaths was lower than reported in the earliest studies.
The overall number of deaths caused by influenza A (H1N1) pdm09 infection was similar to that caused by seasonal influenza and lower than that of previous pandemics [6]. The most common cause of death was respiratory failure [7]. Other reported causes of death included pneumonia, high fever leading to neurologic sequelae, dehydration from excessive vomiting and diarrhea and electrolyte imbalance. Severe cases were most frequent in middle-aged patients, who often had coexisting conditions [7]. Although to date there seems to be no major difference between the virulence of influenza A (H1N1) pdm09 strains and seasonal influenza [8] strains, a more aggressive course in specific populations, such as in young patients and pregnant women, has been reported [8,9].
Further risk factors include obesity, chronic lung disease, chronic heart disease, chronic renal disease, diabetes mellitus, and severe immunosuppression [4,10,11]. Contradictory findings have been reported in regard to varying disease severity during the pandemic season. Although some researchers did not observe any differences in disease severity between the first and second pandemic outbreaks in 2009 [12,13], another study showed a 4-fold increase in hospitalization and a 5-fold increase in number of deaths in the second wave [14]. However, disease severity of postpandemic seasons has been rarely analyzed. We performed a retrospective analysis of all patients with laboratory-confirmed influenza A (H1N1) pdm09 virus infection who were hospitalized at the Tunisian University Hospital, in the postpandemic season 2010-16 to identify possible risk factors associated with severe clinical outcome.

Methods
We conducted a retrospective cohort study of all patients admitted to the University Hospital, with laboratory-confirmed influenza A  (Table 3).

Discussion
In our study, the rate of severely diseased patients with influenza A (H1N1) pdm09 virus infection increased in the first postpandemic season, resulting in an in-hospital ICU mortality rate of 55%. Also, the length of hospital stay in the postpandemic season and the need for mechanical ventilation and ICU admission were significantly higher than in literature. We identified ARDS as the only independent risk factor of mortality. The influenza A (H1N1) infection in 2009 affected Tunisia nearly 700 000 people (6.5% of the population), 179 patients were hospitalized in various Tunisian resuscitation departments [15]. A recent Tunisian study [15], found Delayed hospital admission and delayed antiviral therapy have been associated also with an unfavorable outcome in the general population [11]. The time between initial symptoms and admission to hospital is fairly homogeneous, with a median of about 4 days (IQR 2-7). In our cohort was 7 days (IQR 5-11). We identified pneumonia in 29 patients (72.5%). These findings suggest that the presence of pneumonia is a risk factor for poor clinical outcome and death. Studies have shown that the presence of pneumonia in patients infected with the H1N1 influenza virus was a poor prognostic factor and was associated with an increase in the mortality rate [16]. There were also 11 exacerbations COPD of and one case with severe myocarditis. Several studies have described myocarditis as a severe complicating form of influenza [17,18] and COPD is an independent risk factor for poor clinical outcomes in influenza and hospitalization in intensive care [19].
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Conclusion
In conclusion, our cohort found notable epidemiologic changes and an increased severity and mortality of ICU patients' influenza A (H1N1) pdm09 infections in the postpandemic influenza season. The presence of ARDS at the admission is the only independent factor of mortality. These findings reinforce the need to identify and protect groups at highest risk for adverse outcomes.
What is known about this topic  Among recent studies, younger age, chronic coexisting conditions, morbid obesity and bacterial coinfection have been reported as independent risk factors for severe disease in the pandemic season.

What this study adds
 The presence of ARDS at the admission is the only independent factor of mortality.

Competing interests
The authors declare no competing interest.

Authors' contributions
All the authors have read and agreed to the final manuscript.