Characteristics of Patients Admitted to the Intensive Care Unit in a Spanish Cohort of Influenza Patients

influenza is a highly contagious infection that constitutes a public health problem due to its rapid transmission and associated high morbimortality...


Introduction
Influenza is a highly contagious disease that constitutes a public health challenge every year due to its high transmission and associated morbidity and mortality [1]. Every year 3-5 million serious cases are registered leading to 250,000-500,000 deaths annually [1]. Although influenza viruses cause a self-limiting disease with symptoms such as fever, cough, runny nose, and general malaise, this disease can be complicated by the development of pneumonia and acute respiratory failure, intensive care unit [ICU] admission, and even the need for mechanical ventilation [2,3].
There are risk groups for these complications, including pregnancy [2,4], obesity [2,5,6], advanced age [7][8][9], chronic diseases and immunosuppression [6]. However, in the 2009 influenza A pandemic, one of most relevant findings was the high mortality rate among healthy children and young adults [7,10,11]. Flu is responsible for 1.3% of total admissions to the ICU throughout the year. If we consider the flu season only, this percentage increases to 3.4% of total admissions to the unit [12]. reported and hospitalised, 33% were admitted to the ICU [14].
We therefore face the challenge of influenza every year and we must be prepared. It is essential to understand the characteristics of severe cases since they generate both high morbidity and mortality and healthcare costs. As far as we know, published data are scarce concerning the characteristics of severe hospitalised confirmed influenza cases admitted to the ICU for complications associated with seasonal flu, and most published studies refer to the influenza A H1N1 pandemic in 2009 [2,6]. For this reason, our objective has been to analyse the characteristics of patients admitted to our centre in the 2013-2014 and 2014-2015 seasons, which are two of the seasons with the highest morbidity and mortality in recent years in Spain, and those that have required admission to the ICU.    Table 1).  Table 2).

Discussion
It is estimated that around 5-10% of confirmed influenza cases require ICU admission [2,5]. This is one of the factors that further increases the economic cost of influenza admissions due to the longer length of stay, as we have also confirmed, and increased use of other health resources [15,16]. In addition, it also involves greater morbidity and mortality, as previously described, with a the groups on the general ward or in the ICU. This is a classic risk factor for influenza severity, probably due to local immune disorders and the physical barriers and mucociliary dysfunction typical of lung diseases, along with a high proportion of elderly patients [19].
Obesity has been added in recent years as a risk factor, both

for seasonal and pandemic influenza. In the 2009 A [H1N1]
pandemic, about 50% of cases had a BMI greater than 30 kg/m2 and the frequency of obese patients with influenza in the ICU has increased every year [19]. This metabolic disease is associated with hyperinsulinaemia, hyperleptinaemia and nutritional dysregulation, which seems to be related to a proinflammatory microenvironment that impairs the immune response to the influenza virus, as well as the response to influenza vaccination, despite having an equal serological response to vaccination [20]. Regarding complications, pneumonia is one of the most frequent and severe, involving admission to the ICU and contributing substantially to the morbimortality of the infection, especially in those older than 65 [21]. Some of the coadjutant aetiological mechanisms detected are: the destruction of the respiratory epithelium by the virus, as well as the activity of its neuraminidase, both factors that could increase bacterial adhesion; inflammatory responses to viral infection, which could upregulate the expression of molecules used as receptors for bacteria; bacterial superinfections promoting immunosuppression; and the synthesis of bacterial virus activating proteases [22].
Other serious complications are ARDS, which was developed in half of the cases and which is described as a risk factor, and Vaccination has been shown to reduce the frequency of serious  [28]. Probably the high percentage in our cohort is explained by the protocols of our centre that recommend the use of antivirals in every patient admitted; the length of treatment in the ICU is accordingly longer [29,30]. This study has several limitations. First, it is a single-centre study with a limited number of cases, and consequently the results should be extrapolated with caution to a larger population. Second, since we only collected the variables recommended by the SISS, some interesting aspects have not been addressed. Furthermore, since the data were obtained retrospectively from medical records, we had some lost data. Lastly, long-term morbidity and mortality and readmissions have not been estimated, so this study probably underestimates disease severity.

Conclusion
Male sex and the development of ARDS are two independent risk factors for admission to the ICU, which occurs in up to 10% of all those hospitalised for influenza. These patients have more complications, a longer hospital stay, and higher detection rates of influenza A virus compared with those on a conventional ward.
We must progress the development of specific therapies, as well as influenza vaccination campaigns, to try to reduce ICU admission, since this involves high morbidity and mortality and significant associated social and healthcare costs.

Funding
We have not received any sources of funding.