Hospitalization for bronchiolitis in children aged ≤ 1year, Southern Italy, year 2021: need for new preventive strategies?

Viral bronchiolitis is a common cause of hospitalization in young children. Despite RSV being recognized as the main cause of bronchiolitis presentations in infants, the community burden of RSV infections still remains underestimated worldwide. Severe bronchiolitis mainly affects children aged < 6 months [3‐5]. However, the COVID-19 pandemic altered the epidemiology and seasonality of many respiratory viruses, causing out-of-seasonal outbreaks worldwide [22].

The present study analyzed children aged 0–12 months in the Apulia region of southern Italy who were hospitalized for bronchiolitis in 2021. Most of these children were aged ≤ 3 months, with no differences between boys and girls. Four children aged 0–3 months showed a coinfection with SARS-CoV-2 but none of them required intensive care support, suggesting that the severe clinical picture of children who required intensive care support was not associated with COVID-19. A single center study in the Apulia region found that younger children were more likely to present with dyspnea and require oxygen support, whereas older children were more likely to present with fever and comorbidities [17]. Despite the low prevalence of risk factors, more than 70% of these children required oxygen support. In particular, only 13% of these children were born prematurely, rates lower than in recent studies from Italy (24.5%) and the USA (33%) [23, 24]. Only 12% of the children in the present study had comorbidities, similar to the percentage in a Norwegian study but lower than that reported in children from the USA [24, 25].

It has been demonstrated that most children hospitalized with RSV infection were previously healthy, with only 3% of RSV-infected children in primary care having comorbidities and only 5% born prematurely [26, 27]. These findings indicate that targeting preventive strategies exclusively at high-risk children would have a limited effect on the total disease burden of RSV infection. It has been estimated that 93% of infants hospitalized were ineligible for prophylaxis with palivizumab [28]. The low prevalence of risk factors in this population, making them ineligible for prophylaxis, suggests that an all-infant immunization strategy should be considered after a cost-effectiveness analysis.

Acute seasonal bronchiolitis is an important public health issue, with severe RSV disease having significant economic costs for healthcare systems. RSV was found to reduce health‑related quality of life (HRQoL) almost 40% during the first week after onset of symptoms in patients aged < 2 years, when the illness is most severe [29]. The disease also has an impact on parents/caregivers, as they experience worry, anxiety and distress [29]. A recent Italian study estimated that the mean cost of hospitalization for bronchiolitis in a pediatric ward was more than 5,000 euros, with the cost being higher for hospitalization in pediatric intensive care units (PICU) [19]. Nearly 35% of the children in the present study who required oxygen support needed to stay in neonatal sub-intensive care units, as they needed high flow oxygen administration. Moreover about 13% of patients requiring oxygen administration needed intensive care support (n-CPAP, n-IPPV, endotracheal intubation), with almost 80% being full-term newborns. A previous European study estimated that the average cost of PICU hospitalization for bronchiolitis in children aged < 12 months was four times higher than the cost for hospitalization in a pediatric ward and more than 20 times higher than children managed in the Emergency Department [30]. More than 80% of the children described in the present study were aged 0–3 months. This age range has been reported to be a risk factor for severe bronchiolitis, with hospital admission for bronchiolitis in this age group associated with higher costs [19, 31]. Because almost all the children in the present study requiring hospitalization in the PICU were aged 0–3 months, preventive strategies aimed at protecting this age group, such as maternal vaccination and monoclonal antibody immunoprophylaxis for newborns, could potentially reduce the economic impact of bronchiolitis [19].

Currently, the only approved prophylactic measure is the administration of palivizumab. Palivizumab, however, is expensive, provides short-lived protection, and re-quires up to five monthly doses [32, 33]. The approval of the new long-acting mono-clonal antibody nirsevimab is the next expected advance in RSV prevention. In term and preterm infants, nirsevimab showed an overall efficacy of 75% in preventing ALRTIs requiring medical attention [28]. Moreover, when compared with placebo, nirsevimab showed greater ability to prevent hospitalization and provided a longer duration of protection [34]. Use of this preventive strategy in all infants during their first RSV season has been estimated to reduce direct medical costs 49%, although the costs of nirsevimab could represent a barrier to its implementation [28, 35]. A recent evaluation of the cost-effectiveness of nirsevimab programs in England and Wales revealed that, at a price per dose of £63, a large-scale seasonal program would be a cost-effective strategy for all infants at birth [33]. Moreover, by reducing the numbers of patients infected with RSV, this strategy would reduce the numbers of patients prescribed antibiotics, reducing both costs and the negative effects of antimicrobial resistance on other pathogens [33]. Despite evidence suggesting that antibiotics do not benefit patients with viral bronchiolitis, due to the low rate of bacterial superinfections, the use of antibiotics is still widespread [1, 24, 36].

The study had several limitations. First, data on the etiology of bronchiolitis were available for only 70% of the included patients, with the remaining 30% not undergoing molecular tests for RSV. The recent proposal of the World Health Organization to add RSV testing to existing influenza surveillance systems could lead to the implementation of molecular testing, at least in hospital settings [37, 38]. Second, data on possible coinfection with viruses other than SARS-CoV-2 were not available. The presence of coinfections could have affected length of hospital stay or the need for oxygen support in some patients with severe bronchiolitis.