4. Discussion:
Our study shows a significant impact of bronchiolitis in our setting during the 2022-2023
season. We observed a remarkable number of children requiring critical care and MV,
compared to the last five seasons, and a significant rise in the severity of bronchiolitis as
expressed by increased urgent codes at ED presentation, increased need, and median duration of respiratory support, and increased median length of stay.
We also confirmed a progressive increase in seasonal admissions for bronchiolitis, mostly sustained by RSV which is shown to be persistently more prevalent after the SARS-CoV-2
pandemic.
Conversely, we observed a decrease in SARS-CoV-2 cases, confirming what is known from the literature about the limited role of SARS-CoV-2 as an etiological agent of bronchiolitis [14].
The non-pharmaceutical interventions imposed by the pandemic initially determined a
dramatic reduction in incidence rates of all infections, including bronchiolitis [15-17], followed by a significant resurgence associated with epidemiological changes, including out-of-season outbreaks [6,10,18].
In our setting, as we have previously described, we had an out-of-season resurgence in summer 2021, mainly driven by RSV, followed by an intense and early 2021-2022 bronchiolitis season. In the last season, an unprecedented peak of admissions, with an even earlier start was observed. However, the seasonality pattern seems to be realigning to the pre-pandemic seasons, and the 2023-2024 season may confirm this observation.
Interestingly, as in the out-of-season period (May-August) 2021, we had a significant number of children with out-seasonal bronchiolitis requiring hospitalization in 2023. However, all 2023 cases were sustained by different viruses other than RSV and had a mild disease course.
The so-called “immunity debt”, is one of the possible explanations for these epidemiological events observed worldwide [19]. It refers to the lack of immune stimulation due to the reduced circulation of viral and bacterial agents during the pandemic which may have increased the pool of immunologically vulnerable individuals, specifically children. The ”immunity debt” may be responsible for the increased impact of the disease at the time of the RSV resurgence with the relaxing of the non-pharmaceutical interventions.
In support of this theory, a decline in neutralizing RSV antibody titers was found in infants and women of childbearing age in the Vancouver metropolitan area, over one year (May – June 2020 and February – June 2021) [20].
Usually, infants achieve partial and transient immunity each year by transplacental transfer. The decreased spread of RSV as a result of anti-COVID-19 measures may have reduced the natural protection of the population (including parents) against RSV thus powering the intra-familial transmission. As a matter of fact, in our series, we had a high number of infants aged 3 months or less affected by severe disease.
More than three years after the beginning of the pandemic, the worsening epidemiological trends seem to persist and the observation of such an increase in disease severity must be carefully considered as a substantial warning sign in our setting and demands adequate interventions.
Currently, the only available strategy against RSV is the use of palivizumab, a monoclonal
antibody that guarantees passive immunity in high-risk categories. The use of palivizumab
is limited by high costs and the need for monthly administration throughout the whole RSV season.
Recently, Nirsevimab a highly potent, long-acting, human recombinant monoclonal antibody has been approved for use by the European Medicines Agency [21].
The possibility of administering only one dose at the beginning of the RSV season opens the opportunity for universal prophylaxis for all newborns, not only for at-risk categories.
Indeed, in our series, most of the patients who required intubation and MV were previously healthy infants with no comorbidities and no indication for RSV prophylaxis. This confirms the efficacy of our prophylaxis strategies in at-risk infants, which were modified according to the epidemiological observations of the previous seasons. Moreover, it highlights the urgent need for therapeutic/preventive interventions to protect all newborns and infants without risk factors.
The potential reasons for the observed increase in the severity of bronchiolitis are unclear. Pre-SARS-CoV-2 pandemic studies already showed a rising trend in ICU admissions in
Europe over the last two decades [22], likely due to the increased utilization of non-invasive respiratory support modalities, while the number of patients requiring MV remained stable.
In our hospital, we observed a significant rise in the use of HFNC but, at the same time, we were overwhelmed by the high number of children requiring MV, determining substantial distress on hospital resources and threatening critical care accessibility for other conditions. In ”normal” RSV seasons the number of mechanically ventilated bronchiolitis in our center is unremarkable. For three months during this season, one-fourth of the ICU beds were occupied by patients with severe bronchiolitis.
Nevertheless, the establishment of a new stand-alone pediatric IMCU in our Institute in December 2020 may have helped in relieving pressure on the ICU and saving hospital costs and resources, allowing the management outside the ICU of a significant number of cases not strictly requiring critical care.
Other authors have tried to explain the increase in severity, suggesting also that factors related to the COVID-19 pandemic may have favored the emergence of more transmissible or virulent RSV strains [23], or that SARS-CoV-2 infections may have induced immune dysregulation in children, increasing their susceptibility to other respiratory viruses, such as RSV [24]. However, current data does not appear to support these hypotheses.
A recent study carried out in Rome, Italy [25], found that the intense RSV peak in 2021–2022 was driven by RSV-A phylogenetically related to pre-pandemic strains and therefore was attributable to the immune debt created by pandemic restrictions. Interestingly, as in our study, they observed an increase in disease severity in 2022-2023 with most of the cases sustained by a genetically divergent strain of RSV-B. This genetic divergence may have increased the RSV-B-specific immune debt, being a possible contributor to bronchiolitis severity in 2022–2023. Unfortunately, we did not perform genetic characterization of viral strains and cannot confirm these observations.
Limitations include the retrospective design and the single center setting of the study. Moreover, our findings may be influenced by local factors. In our series, 59% of patients who required MV were referred to our center from local pediatric EDs. This could suggest that intubation may have been a precautionary measure for the transport thus overestimating the severity. However, our hospital has always been the referral center for the Liguria region and the clinical management of bronchiolitis refers to well-defined clinical and therapeutic pathways with no changes in the last decade. Moreover, the ICU Critical Care and ECMO Transfer Team of our hospital oversees all transfers, and intubation was never reported as a precautionary measure in this cohort.
Similarly, although the organization of our hospital was modified at the end of 2020 with the establishment of a new standing-alone IMCU, the management of bronchiolitis in our institution has not changed in terms of clinical and therapeutic decisions.