In this study of children with i RV / EV complex infection living at high altitudes, 47.3% were found to have severe disease that required transfer to pediatric intensive care. Children with comorbidities such as prematurity, heart disease and inborn errors of metabolism were especially prone to severe disease. The clinical course frequently includes ARDS and a mortality similar to RSV, which has traditionally been responsible for a significant burden of disease [8].
The study population’s median age was much lower than that reported in the literature in high-income countries. Sapeder et al., in a retrospective cohort study carried out in Baltimore with 519 patients, showed a median age of 2.7 years (very similar to what we found in our group) for those hospitalized for RV / EV with severe infection [9]. In a study in New York with 155 children, Smith et al. found a median age of 4 years [5].
Vásconez-García et al. have linked nutritional risk and the presence of worse outcomes and high mortality during severe viral respiratory infection in Latin American individuals with comorbidities [10–11]. However, in our population, malnutrition was observed in only 41%, a finding consistent with the dietary problems of low- and middle-income countries where the prevalence of chronic noncommunicable diseases such as overweight is progressively increasing [12–15]
Traditionally, severe ARI has been described in patients with comorbidities. Tijerina et al., in a cross-sectional study in Mexico with 295 patients, described a higher rate of hospitalization in patients with prematurity [16] and bronchopulmonary dysplasia, relating it to the lack of coverage in vaccination, abandonment of breastfeeding, poverty, social commitment and the socioeconomic level [11] [17]. In our population, we found that children hospitalized for RV / EV presented significant comorbidities and frequently needed to be transferred to intensive care. As mentioned previously, this virus has generally been thought to cause self-limited upper respiratory infection in most cases [18], but studies like ours show that, in risk groups, this virus can have a similar behavior in terms of severity to others previously described, such as RSV.
We found that younger patients infected with RV / EV required transfer to intensive care more often and had a longer hospital stay. Roeleveld et al., in high-income countries, found that RV / EV infection, regardless of comorbidities, is not associated with a longer length of hospital stay [19]. The difference in our population can be explained by the greater difficulty in accessing health services in low- and middle-income countries, which often leads to late consultations. This is related to the significant frequency of ARDS seen in our series in children with RV / VE, which is higher than that observed with RSV.
Traditionally, RSV causes significant morbidity / mortality in children under two years of age. The study by Bianchini et al. shows that this virus is the second leading cause of infant mortality and the leading cause of lower respiratory tract infections in children worldwide, with clinical manifestations and severe complications including ARDS [20]. Having seen these results with RV / EV infection, it is striking that this germ had a more aggressive behavior, with a higher frequency of ARDS and viral coinfection and a greater need for respiratory support. This has not been described before in middle-income countries. We consider that it is important to look further into the pathophysiological mechanisms that explain this more severe behavior of RV / EV.
Messacar et al. found that pediatric patients admitted with the RV / EV complex had the same probability of requiring admission to the PICU or mechanical ventilation as children admitted with other respiratory viruses, historically considered to be more severe, such as influenza [21] [22]. In a previous publication by our group, the RV / EV complex was described as the most frequent etiological agent (30%), followed by RSV (19%), parainfluenza (7.4%) and adenovirus (5.7%). Influenza only accounted for 1.2% of the total RT-PCRs taken [23]. In his series, Messacar found that only 18% of the patients with RV / EV required transfer to intensive care, while 60% of our patients were transferred [21]. Socioeconomic factors, comorbidities and limitation of access to health services can explain this situation.
Despite the fact that it has been considered to be a minor infection, the risk of developing ARDS was more frequent with the RV / EV complex than with RSV infection in our population. This is an important fact, and we must consider that children admitted to intensive care with RV / EV infection may have an unsatisfactory course and require more frequent and intense support than those with other viruses such as RSV [5]. Comorbidities such as prematurity, heart disease and inborn errors of metabolism may partially explain this evolution, but this implies that, in these risk groups, RV / EV infection cannot be considered to be a mild infection, and its possible complications must be taken into account [5].
We consider that our study has several limitations. In the first place, it is the experience of a single university center that only evaluated children who, due to their severity, required hospitalization. This may be an explanation of why children with some comorbidities may require more transfers to intensive care. However, RV / EV infection was more severe and frequent in patients with comorbidities than RSV was in the same group. Another limitation of our study is that we did not have a control group with a negative RT-PCR and ARIthat required a transfer to intensive care. However, when compared with RSV, we observed that the RV / EV behavior is more severe and has a more aggressive natural course. Additionally, the commercial brand of RT/PCR did not allow us to differentially evaluate the enterovirus and rhinovirus to understand the differences between these viruses from the same family [24]. In general, they are analyzed together in most of the tests available commercially today.