Our results suggest that infants with severe LRTI and positive PCR for HRV, alone or in co-detection with RSV, stayed hospitalized longer periods and utilized more supplemental oxygen, when compared to children infected by other viruses, including those with RSV-alone. Our data also reinforce previous findings that identified RSV as the major agent associated with severe LRTIs among children in a hospital setting, in populations of low socio-economic status, where other environmental and social variables potentially play a role [16, 17]. Infants younger than six months and those with a family history of asthma/recurrent wheeze are also at greater risk for disease severity.
RSV was the most frequently detected virus, accounting for a high burden of LRTIs in our population. Although it is not possible to establish an unequivocal correlation between LRTIs and upper airway viral detection, the finding of RSV in over 50% of hospitalized children in our study strongly suggests that its impact is still indeed very high in this region, regardless of the presence of newly identified viruses. These results are in accordance with recently published studies in Brazil, which also identified RSV as the main agent responsible for severe LRTI, especially in a hospital setting. Nascimento and coworkers have shown an overall viral detection rate of 93% from nasopharyngeal samples in a small group of children below 2 years of age, and reported RSV as the most prevalent virus (63.6%) . Another study aiming to investigate the role of HBov and hMPV in LRTIs in southern Brazil also showed similar results (at least one positive virus in 90% of the samples and RSV positive in 49.3%) . The high detection rate of RSV in children with LRTI in a hospital setting such as ours is consistent with most studies worldwide and the burden due to viral respiratory disease seems as high in these locales as they are in more developed countries. A recent analysis of children admitted into the hospital due to acute bronchiolitis in Texas, USA, has shown a steady increase in admissions over a 5-year period and this has been credited mostly to RSV . This increasing role for severe viral LRTIs, observed also in other studies, is probably explained by a series of complex environmental and social changes that seem to affect how viruses spread in communities.
Some studies have reported different clinical outcomes for specific viruses causing LRTIs, especially in the presence of co-detections, such as with RSV and HBov [22, 23], while others did not reproduce such findings [17, 24, 25] and these associations remain unclear. A lack of association between an overall finding of any viral co-detection and LRTI severity was reported in studies performed in non-affluent countries [2, 12, 26], as well as in developed countries [13, 14]. In our study, patients detected with HRV alone and RSV + HRV presented increased length of hospitalization and increased time of supplemental oxygen use. Papadopoulos et al. has shown a five-fold increase in clinical severity in infants with acute bronchiolitis due to HRV, compared to those infected only with RSV. Compared to those with positive RSV samples without HRV co-detection, infants with HRV were older, had lower birth weights and were hospitalized earlier . Some explanations for apparently contradictory findings in a myriad of studies could be attributed to the lack of uniform criteria for subject inclusion and standardized statistical analysis . Other plausible explanations are the natural variation in HRV prevalence in different seasons and possible variations in the prevalence of type C HRV. This agent is associated with more severe disease and was already described as a major cause of LRTI in infants from non-affluent countries [27, 28]. Unfortunately, in our study, we were not able to determine the prevalence of HRV subtypes, and this stands as an interesting subject for further research.
The association of HRV (alone or with RSV) with LRTI severity and atopy has not been widely studied. The relationship between persistent wheezing at 3 years and at 6 years versus relevant HRV infection in early life is well established [9, 29], but there are few studies looking at these relationships in the first year of life. A recent study suggests that the relationship between HRV in early life LRTI and subsequent recurrent wheeze/asthma is dependent on allergic sensitization, which seems to precede the viral insult in a causal model . This association we have found between HRV with increased severity (using the surrogates of length of hospital stay and days in supplemental oxygen) is a major finding. Hence, the association between HRV infection, increased severity and atopy remains to be better clarified.
It has already been shown that HRV is able to reduce cell proliferation and decreases the self-repair capacity of bronchial epithelial cells . Therefore, our data may suggest that in certain subsets of patients the burden of HRV in acute LRTI should be considered distinct from that of other viruses. Another plausible explanation for our findings could be the possibility of HRV persistence in the airways leading to an “over detection” of the virus, simultaneously with those infected only by RSV . In our study this hypothesis seems improbable since we detected a clear worsening in the clinical markers in patients with RSV that were also detected with HRV.
Another interesting finding of our study was the high prevalence of newly described viruses. hMPV was detected in almost one third of all episodes, but did not seem to affect the main outcomes studied here, in the way RSV and HRV have done. While the recognition of the impact of human hMPV is increasing, its prevalence is still probably underestimated in clinical practice, since laboratory testing has become widely available only in recent years [18, 24, 33]. HBov was also detected in a large number of nasal samples and it was very frequently associated (co-detected) with other agents. In our study, only 2/27 patients with HBov had this virus detected as single agent. The overall HBov detection rate was higher in our data compared to previous studies [34, 35], and this may be explained again by natural seasonal variations. It is also interesting to notice the seasonal pattern of both hMPV and HBov, which present their peak prevalence rates in late winter, right after the RSV peak, which occurs earlier in winter.
The main limitation of our study is the lack of surveillance in consecutive years, which could have biased results in case of an outbreak of one specific virus in a given year. Our eight months of viral surveillance could potentially have failed to detect any atypical outbreak, which did not seem likely to have occurred. Also, reliable tests capable of ruling out bacterial co-detection were not available at the time of the study. This could have underestimated the burden of bacteria in our sample and the co-detection of viruses and bacteria remains an interesting issue for further studies.