This study describes 100 cases admitted due to flu syndrome or acute respiratory infection.

The global hospitalization rate was 16.8 cases per 100,000 inhabitants. The specific rates by age groups showed patients under 10 years of age to have the highest hospitalization rate attributable to the disease, particularly infants under two years of age, with 69.8 cases per 100,000 inhabitants, while the lowest rate corresponded to patients between 10 and 17 years of age, with 7.5 cases per 100,000 inhabitants.

The 100 cases included in the study were admitted to this hospital between 7 July and 29 December 2009. The median age of the patients was 38 years (minimum: 4 months, maximum: 80 years). Most of the patients resided in the Community of Madrid (94%) (Table 1).

Full information on the initial symptoms of the disease was available for 25 of the 100 patients included in the study (25.0%). Fever and general discomfort were present in over 90% of the cases, followed by cough in 88%, dyspnea in 48%, and symptoms such as sore throat, rhinorrhea and headache, in 20–40% of the cases. The median time from onset of the symptoms to admission was three days (minimum: 0 days, maximum: 17 days). Of the 100 patients, 77 (77%) had at least one risk factor for severe influenza (Table 2), including 60.7% of the children (<18 years) and 83.3% of the adults (≥18 years); in turn, 46% presented at least two factors, and all the patients aged 65 years or older suffered some background disorder. Asthma was the most common disease among the children (28.6%), while the adults showed a predominance of smoking (30.6%). Seizures, cognitive dysfunction and neuromuscular diseases were more common among the younger patients (17.9%) than in the adults (8.3%). None of the patients were pregnant at the time of admission (Table 2).

Upon admission, 15 out of 96 patients with information corresponding to the complete blood count (15.6%) presented leukopenia, 24 (25.0%) anemia, and 21 (22.3%) thrombocytopenia (Table 3). Of the 48 patients diagnosed with pneumonia, 11 (22.0%) yielded positive cultures (4 blood cultures and 7 sputum or other respiratory sample cultures). Streptococcus pneumoniae was the most frequent microorganism (36.3%), followed by Pseudomonas aeruginosa (27.2%), and each of the following: coagulase-negative Staphylococcus, Haemophilus influenzae, Escherichia coli and Stenotrophomonas maltophilia, in 9.0% of the samples. In the remaining 37 patients, no microorganisms were isolated from the analyzed samples.

Of the 98 patients with chest X-rays upon admission, 47 (48.0%) showed some infiltration; the median age of these patients was 36 years (minimum: 1 year, maximum: 80 years), and 66.0% had at least one risk factor. The radiological findings included bilateral infiltrates in 22 patients (46.8%) and infiltrates confined to a single lobe in 25 (53.2%).

Of the 100 patients, 94 (94.0%) received antiviral treatment. In all cases the medication consisted of oseltamivir, except in two cases (2.0%), where oseltamivir was followed by zanamivir. In 80 patients with information on the starting date of antiviral treatment, the median time from onset of the symptoms to the start of therapy was three days (minimum: 0 days, maximum: 18 days); 36 (45.0%) received the antiviral agent in the first 48h after symptoms onset, 5 (6.3%) received the treatment before admission to hospital, 70 (87.5%) received therapy in the first 48h after admission, and 5 (6.3%) received it more than 48h after admission. The median duration of treatment with oseltamivir was 5 days (minimum: 5 days, maximum: 22 days), versus 36 days for zanamivir (minimum: 6 days, maximum: 67 days).

Of the 100 patients analyzed, 19 were admitted to the ICU and two died of the flu. Seventy-nine percent of those admitted to Intensive Care had at least one risk factor. Ten of these subjects (52.6%) required mechanical ventilation, 7 (36.8%) developed acute respiratory distress syndrome (ARDS), and three (15.8%) had a clinical diagnosis of sepsis. All the patients received antiviral treatment with a dosing regimen that did not differ from that described above.

The median hospital stay of the patients admitted to the ICU was 7 days longer than in the case of the ward patients; this difference proved statistically significant (p<0.001).

The first death due to pandemic flu occurred in a 14-year-old girl with Lennox-Gastaut syndrome who developed septic syndrome with consumption coagulopathy secondary to acute respiratory infection with influenza A/H1N1 2009 and possible bacterial overinfection. The second fatality corresponded to a 60-year-old male without known risk factors for flu complications, admitted to the ICU due to acute respiratory failure secondary to influenza A/H1N1 2009 pneumonia, with severe hypoxia, oliguria and hypotension. Both patients received antiviral treatment upon admission to hospital – the girl within 48h after symptoms onset, and the adult 7 days after symptoms onset.

In the bivariate analysis, the patients admitted to the ICU showed a greater probability of suffering metabolic disease, including diabetes, and some infiltration on the chest X-rays upon admission, than those patients not admitted to the ICU (Table 4). In contrast, no difference was observed in the median time from symptoms onset to hospital admission between these patients. Likewise, no differences were observed in relation to vaccination against seasonal influenza 2008–2009. In a multivariate analysis considering modeled upon maximum metabolic disease, the presence of infiltrates in the chest X-rays upon admission, and cardiovascular disease, the first two variables were significantly correlated to admission to the ICU.

In contrast to seasonal flu epidemics which are associated with higher hospital admission rates among individuals over 65 years of age and infants under two years of age, the incidence of hospitalization due to pandemic flu in this study was greater among subjects under 10 years of age.14 The hospital admission rate in patients over 65 years age was comparable to that of the group with the lowest incidence (10–17 years of age). The estimated rates could underestimate the true hospital admission rates due to pandemic flu, considering that the numerator does not include those patients with flu residing in Healthcare Area IV but admitted to a hospital pertaining to some other healthcare area in the Community of Madrid. The absence of pregnant women in this study is due to the lack of an Obstetrics Department in the hospital – those pregnant patients requiring admission being referred to another reference center.

In the same way as in other published series,17,18,24 the largest proportion of admissions due to pandemic flu in our center involved young individuals between 18 and 49 years of age – those under age 65 representing close to 90% of all admissions. This discrepancy between the incidence of hospitalization and the proportion of admissions by age intervals is explained by the population distribution of Healthcare Area IV, where 47% of the recruitment population is between 18 and 49 years of age, and only 10% is under 10 years of age.

Over 80% of the adults and 60% of the children had some risk factor for severe seasonal influenza. The prevalence of these factors in our series is higher than in other studies, in both adults and children admitted to hospital because of seasonal flu.15,25–27 This difference can be explained by the reasonable tendency among physicians to preferentially decide admission of those patients with risk factors for flu complications. In the same way as in seasonal flu, chronic respiratory disease, chronic obstructive pulmonary disease (COPD) and asthma were globally the most frequent risk factors among the admitted patients.

A review of the literature shows that the early administration of oseltamivir in patients with pandemic (H1N1) 2009 viral infection can shorten hospital stay and reduce the risk of progression to serious illness requiring admission to the ICU or potentially capable of causing death.13 There is evidence that antiviral treatment started within 48h after symptoms onset affords increased benefit.13 In our analysis, the patients admitted to the hospital ward did not show a greater probability of having received oseltamivir in the first 48h of disease onset than those patients admitted to the ICU because of flu.

A body mass index of ≥28kg/m2 been cited as a risk factor for severe pandemic flu.12,15,17–19,22,23 The latter is also associated to other comorbidities that are known risk factors for complicated flu disease, such as diabetes, metabolic disorders, and cardiovascular and pulmonary diseases (obstructive sleep apnea and hypoventilation syndrome and obesity). In this study, the absence of a statistically significant association between obesity and severe disease could be explained by the limited number of event analyzed. However, the results of the multivariate analysis are concordant with those studies that point to metabolic disorders as risk factors for severe influenza.12,28,29 The presence of chest X-ray infiltrates has also been cited as an independent risk factor for severe pandemic flu in the medical literature.17 In our series, 98% of the patients with such radiological findings were diagnosed with pneumonia, and 75% of those admitted to the ICU presented this complication.

In our patients, as in other series, abnormal X-ray findings at the time of admission, together with the presence of certain comorbid conditions – particularly metabolic diseases–suggested a more serious course of the illness.