Respiratory viral infection is a major source of morbidity and mortality in childhood. Just over one-third of preschool-aged children develop lower respiratory infections during their first year of life. Between 1% of 2% of these patients require admission to hospital.1,2

The etiological agent is not always identified in these patients. Children with respiratory infections are generally treated as outpatients and the etiology of their disease is not investigated. If they are hospitalized, the commonly employed evaluation techniques are often not sufficiently sensitive.3

Experience and understanding of the role of viral coinfections in respiratory infections has grown in recent years, thanks to the introduction of molecular techniques.4–6 At present, the clinical data available on coinfection, in terms of both the number of viruses involved and the severity of the condition, are variable and even, at times, contradictory. These discrepancies may be due to factors that affect the various etiological agents, such as geographical region and methods of detection employed.

The aim of this study was to analyze the viral etiology of respiratory infections and the real clinical implications of coinfection, and its possible relationship to clinical severity in a population of hospitalized patients in a general hospital located in Barcelona with a secondary-level pediatric department. Etiology was determined using multiplex polymerase chain reaction (PCR) and low density microarrays.

Samples from 463 pediatric patients admitted to the Pediatrics Department of the Hospital del Mar, Barcelona, for community-acquired respiratory infections were analyzed. Results were positive in 385 (83.15%) samples. Age distribution was as follows: younger than 12 months, 173 (44.94%), from 12 months to 3 years, 143 (37.14%), from 3 to 5 years, 53 (13.77%) and older than 5 years, 16 (4.15%); 44.94% of the cases were under the age of 12. None of the patients had risk factors for respiratory diseases. Clinical diagnoses of the positive patients were as follows: 100 cases of bronchiolitis, 92 pneumonia, 81 bronchitis, 80 upper respiratory tract infection, 25 influenza-like syndromes, six pertussis and one newborn with risk of infection (Table 1).

Viruses detected are shown in Fig. 1. The five most common viruses in both study periods were RSV-B (139 cases), rhinovirus (114), RSV-A (111), influenza virus serotype A H1N1/2009 (93) and bocavirus (77). The percentages of codetections in each period were: (a) in 2009, 69.79% of infections were caused by more than 1 viral agent (134 of 192 infections detected); (b) in 2010, the proportion was 53.88% (104 of 193 infections detected). The most common coinfections were rhinovirus+RSV-B in 10 cases and RSV-A+RSV-B in 5.

Fig. 1.

Viruses isolated in 2009 and 2010 in 385 children hospitalized in the Pediatric Department of the Hospital del Mar, Barcelona, for community-acquired respiratory tract infections.

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Coinfection was found in 61.81% of samples from positive patients. Of these, two viruses were found in 36.36%, three viruses in 16.10% and four or more viruses in 9.35%.

We found a shorter hospital stay in patients with a greater number of viruses (P<.001), as reflected in Table 2; the association was linear.

The 103 patients who required oxygen therapy (basal saturations≤92%) are described in Table 3. When these data were correlated, it was revealed that the younger the patient, the more frequent the need for oxygen therapy, a trend that was statistically significant (P<.001), and the greater the number of viruses detected the less need for oxygen therapy (P<.001).

Admission to the PICU for mechanical ventilation was required in nine cases. Age, clinical presentation, viruses detected and diagnosis are shown in Table 4. The predominant etiological agent in these patients was RSV. No statistically significant differences were found when viral coinfection was correlated with the need for mechanical ventilation in the PICU (P=.69).

A clinical suspicion of bacterial coinfection based on the patients’ clinical picture and acute phase reactant values was determined in 37 cases (8.50%). However, this was confirmed in only two cases, in which Streptococcus pneumoniae was confirmed in a positive blood culture or PCR. One virus was detected in 20 cases and two viruses in 14 cases. Hospital stay for 27 patients was between 1 and 4 days and between 5 and 10 days for 10 patients. In the eight cases with a diagnosis of atypical pneumonia on serology, viral coinfection with a single virus was detected in 5.

The first finding of significance is the high rate of positive results in the population without risk factors (83.15% of samples studied) and the high rate of coinfection (61.81%), particularly in the first year of the study (69.79%). In the literature, coinfection rates range from 8% to 76%, depending on the series.7–16 With regard to the severity of our cases, it is important to note that a greater number of viruses is not synonymous with greater severity. According to our results, the number of viruses detected is in inverse proportion to the need for oxygen therapy and days of hospital admission; this relationship was statistically significantly (P<.001). However, of the nine cases admitted to the PICU, more presented coinfection, but this was not statistically significant.

Some studies have reported no clinical differences between patients with respiratory infections caused by a single agent and those caused by multiple viruses detected in nasopharyngeal aspirates from hospitalized children.8,11,13,17–23 Of interest is the study performed by Camargo22 in Sao Paulo during the H1N1 influenza epidemic of 2009, in which 21.9% of cases had coinfection not associated with greater morbidity or mortality. In contrast, other studies show that coinfection is a risk factor for poor progress.14,23–28 One of the most important of these was performed in Vienna by Aberle et al.,14 between 2000 and 2004. They reported that airway obstruction was more severe when RSV contributed to the coinfection, and mean hospital stay lengthened if rhinovirus was involved. In another study, Grensill et al.26 showed that when the coinfection consisted of RSV and metapneumovirus, progress was poorer. Furthermore, Richard et al.,28 who studied the relationship of coinfection with need for PICU admission, concluded that the presence of two or more viruses increased the likelihood of PICU admission 2.7-fold. However, in another study conducted in patients admitted to the PICU, Ghani et al.29 found that only bacterial confection was associated with a longer hospital stay, with no increase in mortality.

We should also remember that the detection of more than one virus may be due to the presence of viral fragments persisting for up to 5–6 weeks after onset of symptoms,14 which may not have any real role in the pathogenicity of the clinical process.30 Relationships may be established with the help of epidemiological techniques, but the use of quantitative techniques would be much more useful for interpreting the contradictions produced by attributing greater or lesser severity to coinfections.

One important limitation of this study of the role of coinfection in upper respiratory tract infections is the small number of cases evaluated, compared to the high number seen in normal pediatric practice. The vast majority of cases do not need hospitalization, and this limits our knowledge of the real situation and prevents us from extrapolating our data to the general population. One final issue that remains unclear is the long-term effect that these coinfections may have on the respiratory system and the development of chronic lung disease.

Although an inverse relationship was found between the number of viruses detected in nasopharyngeal aspirate, the need for oxygen therapy and hospital stay, the results of our study differ widely from the data published by other groups. More epidemiological studies and improved quantitative detection techniques are needed to define the role of viral coinfections in respiratory disease and how they correlate with clinical severity.

The authors state that they have no conflict of interests.