RSV and hMPV are frequent causes of hospitalization among young children [2–6, 17–19, 21–28]. RSV was the most common etiology of hospitalization for ARTI among children in our hospital during the winter 2014-2015 whereas hMPV was found in a much smaller proportion of children as reported in the literature [15, 27, 29]. Our study refers to one of the longest period of observation published for hMPV infection. Both viruses show a preferential but distinct seasonality with a predictable peak for the RSV in November and December in Belgium and epidemics of hMPV occurring in late winter or early spring as previously reported [18, 19]. Nonetheless, the recent impact of COVID-19 pandemic and lockdowns may affect the predictability of upcoming outbreaks of RSV as recently seen in Australia .
Molecular diagnostic tests remain the gold standard for the detection of respiratory viruses, but they are more costly and only reimbursed by the Belgian social security for children in intensive care units or in oncologic wards. Using molecular rather than non-molecular diagnostic tests could impact therapeutical strategies, the prescription of antibiotic drugs or the duration of hospitalization [31, 32]. However, PCR methods can detect resolved infections and interfere with the objectivity of the results including cured, asymptomatic or even ill patients enduring another viral infection or a bacterial superinfection. If molecular diagnosis is not available or not deemed necessary, the use of antigen detection tests and viral culture are other options . When an antigen detection test or a cell culture is positive for a specific virus, the probability of its implication in the actual infection is thus higher, making this kind of tests a good choice when studying disease symptoms. We could confirm the lower sensitivity of viral culture for hMPV than for RSV detection . In contrasts with other publications, we observed more co-infections with hMPV than with RSV in children hospitalized, [18, 33]. This could be explained by the longer period of observation in the hMPV group which may result in a longer exposition to other germs.
The age distribution of children infected with RSV infection is similar to another Belgian study, RSV showing a peak in children younger than 3 months, while for hMPV, the peak is around 6-12 months . The younger age of children hospitalized for RSV infection than for hMPV infection is concordant with the literature [12, 15, 16, 34]. In contrasts with other studies, we observed a significantly higher proportion of children born prematurely, but not extreme premature, in the RSV group than in hMPV group [14, 23, 35]. Preterm birth is a well-known risk factor for severe RSV infection . Belgium follows the international consensus on the Palivizumab policy and reimburses this prophylaxis during the RSV season in all infants born before 28 weeks gestational age . This is probably the reason why extreme prematurity was not increased in the group of RSV infected children. Other comorbidities such as chronic respiratory disease were more associated with hMPV in concordance with other publications [16, 17, 23, 35], but did not remain significant after adjusting for age and gender. Nevertheless, much remains to be discovered in hMPV infections in order to propose a vaccine strategy for children with risk factors for severe disease [9, 10].
In our observation, children hospitalized with RSV infection suffered from more severe respiratory involvement requiring frequently supportive treatments, whereas children with hMPV were more often febrile, diagnosed with pneumonia and treated with antibiotics. Literature comparing RSV and hMPV infections is controversial. If some studies did not report any difference between RSV and hMPV infection in children , others reported that non-specific symptoms such as fever or gastrointestinal complains were more related to hMPV [14, 15, 23] while respiratory symptoms or feeding difficulties were more associated with RSV [16, 34]. It is also recognized that RSV and hMPV can differ in X-ray patterns . Although inconsistently, hMPV has been associated with more pneumonia than RSV [14, 15, 39]. Furthermore, our study shows more frequent pulmonary infiltrates in females. In a Canadian prospective study, Papenbourg et al reported that females with hMPV infection experienced more severe disease . Our data did not show any increased morbidity in female. However the demonstration of pulmonary superinfections by chest x-ray has limtations, the emergent use of lung ultrasound to diagnose pneumonia seems more sensitive .We found no difference in the rate of hospitalization between these 2 viruses but we observed longer hospitalization for RSV than for hMPV infection which is not in line with other studies [11, 13, 16, 42].
Our study presents some limitations. Related to the retrospective design, data collection was based on non-standardized medical charts completed by different physicians. As a result, missing data are numerous. The indication for a NPA or a NPS was not standardized which may result in an overestimation of hospitalization rates related to each virus. While our number of hMPV infected children is one of the biggest in European publications, we compared 8 years hMPV circulation with only one RSV season. As the pathogenicity of RSV vary from one year to another, one year might not be representative of the pathogenicity of RSV. Finally, identification of the viruses were not based on molecular methods antigen detection tests and viral culture are less sensitive than molecular methods for the detection of RSV and hMPV, but the sensitivity of rapid antigen methods are closer to the one of molecular tests for patients with recent symptoms [42, 43].
To conclude, despite their genetic resemblance, RSV and hMPV are leading to two distinct clinical entities. hMPV is is an important source of pneumonia, requiring hospitalization with more antibiotics administration and is more often present with co-infection.
RSV is 10 times more prevalent, the epidemic starts earlier and causes more severe symptoms in youngest children with more respiratory distress requiring oxygen administration or respiratory support, and a higher rate of transfer in a PICU compared to hMPV. Recent trials for a RSV maternal vaccine using transplacental transfer of maternal antibodies strategy are promising perspective .