Increased bronchiolitis burden and severity after the pandemic: a national multicentric study

In high-income countries, bronchiolitis represents the leading cause of infant admission at the hospital [1], causing a significant burden for emergency departments (ED) and paediatric wards due to clinical care requirements, number of cases and seasonal distribution with a typical winter peak led by respiratory syncytial virus (RSV) [2, 3]. Bronchiolitis may often induce the need for respiratory or nutritional support representing a leading cause of admission to paediatric or neonatal intensive care units (ICU) in the most severe cases [4]. During the SARS-COV-2 pandemic, social distancing and masking measures profoundly changed viruses’ distribution and seasonal patterns, determining a nearly complete disappearance of viral bronchiolitis with a very different seasonality [5‐7]. The withdrawal of these measures resulted in an unusual seasonal distribution of hospitalization for bronchiolitis the following year with a precocious and higher peak but a similar overall number of cases due to a faster reduction [8, 9]. Surprisingly, after the pandemic there was also an increase in the use of high flow nasal cannula (HFNC) and in the admission to ICU [8]; whether this change is attributable to a more severe disease or a change in the attitude of physicians after the pandemic is to be determined.

The study aims to establish the trend in need for bronchiolitis-related hospitalization, severity and microbiological characteristics during the last five years in Italy.

We conducted a retrospective study in six Italian hospitals: Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste; Bambino Gesù Children’s Hospital IRCCS, Rome; Vittore Buzzi Children’s Hospital, University of Milan, Milan; ASST Spedali Civili, Brescia; Ca’ Granda Ospedale Maggiore Policlinico, Milan; Ospedale Regionale Ca Foncello, Treviso. We retrospectively reviewed medical records of all children (< 1 year) hospitalized between 1st September and 31st March (winter season) of every subsequent year since September 2018. We included for the analysis all the patients with a final diagnosis of bronchiolitis at discharge as reported by the clinical records ICD 9 codes 466.11 and 466.19.

For every patient, we collected the following data: age, sex, gestational age and weight at birth and underlying comorbidities, defined as any disease already present at the bronchiolitis onset. The comorbidities were grouped, according with the literature [10], into the following five groups: ex-preterm, patients with neuromuscular disease, patients with congenital heart disease, patients with chronic lung illness, patients with immunodeficiency. We collected data on virologic results of polymerase chain reaction (PCR) panels capable of detecting at least 5 viruses nasal or pharyngeal swabs or aspirates, date of hospitalisation and discharge, admission to the ICU and length of ICU stay, need for and days spent on oxygen therapy, high flow nasal cannula (HFNC), non-invasive and invasive respiratory support, respectively.

This study describes a marked increase in the absolute number of hospitalizations for viral bronchiolitis during the last winter season, and the severity of disease course is defined as a higher percentage of ICU admissions and MV rates. In particular, the number of children who were hospitalized for viral bronchiolitis in the 2022–2023 winter was roughly double compared to the pre-pandemic seasons and presented a 70% increase compared to 2021–2022 winter season. Our study is the first one reporting such a post-pandemic abrupt increase in bronchiolitis-related hospitalisation and growing severity.

It could be due to the combined effect of the complete removal of restrictions on the 25th of March 2022 in Italy (dl n.24 22G00034) and to [11] the relaxation of self-imposed anti-infective rules by parents.

The abrupt and precocious fall in the number of patients presenting an RSV infection in the January of 2022 resulted in a more extended RSV-free period this year, leading to an enlarged gap between the possible last maternal RSV infection and the delivery. This phenomenon may have reduced the effectiveness of the transplacental immunoglobulin newborns’ coverage [12], causing a less effective passive immunisation of the infants [13], thus justifying a more severe disease presentation with an increased need for hospitalisation.

However, despite the different total amount of hospitalisation last winter, the monthly distribution of cases was much closer to the pre-pandemic period, thus suggesting a less naive population than what was speculated for the 2021–2022 winter and, therefore a slower spreading of RSV [14].

From this perspective, this increase may also be partially explained by a rise in coinfections. After the pandemic, the higher prevalence of coinfections of RSV and other viruses, such as rhinovirus, may result from the transmission of multiple viruses at once by the same subject that presents an immune debt [15]. The coinfection phenomenon in these patients is consistent with the co-dissemination of social contagion theory, which relies on the synergy between viruses rather than the competition if the patient encounters them quickly before an effective immunological response [16]. Influenza virus was completely absent through the 2020–2021 winter, probably due to social distancing and COVID-19 containment measures as already reported. On the contrary the absence of influenza virus in the 2021–2022 winter season in patients with bronchiolitis is in contrast with the partial resurgence of this particular virus reported in adults that year [17]. The last winter season influenza more than doubled compared to the baseline represented by the two pre-pandemic winter seasons. With this sort of delay in its resurgence influenza virus constitute a unicum in our study that is yet to be understood.

Another remarkable finding is the trend of influenza virus that was never detected in our patients during the containment measures and the following year [18] but spread during this winter season to reach a higher incidence compared to the pre-pandemic years.

Concerning disease severity, we noted that the percentage of subjects admitted to ICU, length of stay and the need for respiratory support presented a marked increase throughout the years. Firstly, last winter, the number of patients requiring intubation quadrupled compared to the previous years. HFNCs were utilized more frequently than oxygen (61% vs 53%). Remarkably, this winter, 80 patients received HFNC with room air in this series, possibly as a consequence of the endorsement given by the guideline to use HFNC to administer a minimal positive end-expiratory pressure [19], notwithstanding the weak evidence sustaining the efficacy of this device in preventing respiratory failure in bronchiolitis [20]. This unprecedented finding outside of clinical studies on HFNC raised concerns about the need for a more precise indication for the use of HFNC [21].

The trend toward a more aggressive approach to treating bronchiolitis has been debated recently. possibly motivated by the increased availability of relatively more advanced respiratory support outside the intensive care units [22‐24]. In particular, the broad availability of high-flow nasal cannula seems to play a crucial role in this process, and it has been reported as paradoxically even leading to an increase in mortality [25‐28]. A remarkable finding of our study is that despite the increased HFNC use this winter, the number of MV patients contextually reached its peak and the length of hospital stay was higher. Increased severity of the disease may determine these data. However, it may also support the hypothesis of a lack of efficacy of HFNC in pre-empting the need for MV, as recently reported, in contrast to previous findings [29, 30]. Remarkably, The HFNC use remained stable at 29% until the pandemic winter season and grew the following winter to 53% and 61% the past winter. This hit suggests that physicians may have developed a different attitude in treating respiratory distress more aggressively during the pandemic [31].

Although statistically significant, the raised NIRS use in our study is less pronounced than the massive augmented use of HFNC since the pandemic. On the opposite side to HFNC, the efficacy of NIRS to reduce the necessity for intubation is established [32]. Despite the extensive usage of these effective devices, we also registered an abrupt increase in the intubation rate this winter. The trend favouring more aggressive management of patients with bronchiolitis [33] cannot be addressed for the whole phenomenon, including intubations. It seems unlikely that an attitude change could be addressed for such an increase in NIRS usage and this significant growth in the intubation rate; moreover, although only close to the statistically significant figure, the length of stay in the ICU also extended this year. From our perspective, the data suggest that this year patients experienced, on average, a more severe disease, with a higher need for advanced respiratory support and intubation rate. The lack of a clear explanation of this newly discovered phenomenon might partly be a consequence of the expected lowering of maternal antibodies to the anticipation of the RSV season the past winter [13]. However, it should not be addressed for the whole phenomenon, and we speculated about the role of a likely immunological debt [15] due to the profound reduction of virus circulation during the pandemic [17]. On the other hand, the increase in hospitalization may be the consequence of an overall more severe course of the disease due to the “immunological debt” and the higher rate of coinfections in the 2022–2023 winter season that seems to play a role in disease severity in contrast with the pre-pandemic literature that reports similar bronchiolitis severity for patients with and without coinfections [26]. However, it could be speculated that patients from the previous literature were not coming from a background of lack of exposure to infections as the post-pandemic ones.

This study shows a significant increase in hospitalisations and disease severity for bronchiolitis in infants and invasive respiratory support in the 2022–2023 winter season. Coinfections have played a major role in the hypothesis of a post-pandemic immunological debt, but more data are needed to confirm our results.