Disease Burden of RSV Infections and Bronchiolitis in Young Children (< 5 Years) in Primary Care and Emergency Departments: A Systematic Literature Review.

Respiratory syncytial virus (RSV) is the most common cause of acute respiratory infections in young children. Limited data are available on RSV disease burden in primary care and emergency departments (EDs). This review synthesizes the evidence on population-based incidence rates of RSV infections in young children (< 5 years) in primary care and EDs. A systematic literature review was performed in PubMed and Embase. Studies reporting yearly population-based RSV incidence rates in primary care and EDs were included. A total of 4244 records were screened and 32 studies were included, conducted between 1993 and 2019. Studies were mainly performed in high-income countries (n = 27), with 15 studies in North America and 10 studies in Europe. There was significant variability in study methodology and setting among studies, resulting in considerable variability in reported incidence rates. Incidence rates were higher in primary care-ranging from 0.8 to 330 (median = 109) per 1000 population-compared to EDs (7.5-144.0, median = 48). The highest incidence rates were reported in infants. Additionally, incidence rates were higher in high-income countries and in studies using laboratory-confirmed RSV cases compared to studies using bronchiolitis ICD-codes (non-laboratory confirmed). Our study found that a substantial number of children under 5 years of age attend primary care settings and EDs, every year for RSV infections. Due to the considerable heterogeneity in study methodology, it was impossible to draw definitive conclusions regarding factors explaining differences in reported incidence rates. Additionally, more studies in low- and middle-income countries are recommended.

Distinct clinical characteristics of bocavirus and Mycoplasma pneumoniae infection in children plastic bronchitis.

BACKGROUND: This study investigated clinical and laboratory characteristics of human bocavirus type 1 (HBoV1)-plastic bronchiolitis (PB), Mycoplasma pneumoniae (MP)-associated plastic bronchitis (PB) and MP-NPB in children, highlighting inflammation, coagulation, and bronchoscopic needs. METHODS: Data on preschool children with PB during HBoV1 or MP infection were collected, comparing MP-PB to severe Mycoplasma pneumoniae pneumonia. RESULT: Compared with the MP-PB group, the HBoV1-PB group, with younger children, had significantly milder clinical symptoms but higher WBC counts (p = .028). The MP-PB group exhibited notably elevated Fibrinogen (p = .045) and d-dimer levels (p < .001). When contrasting the MP-PB with the MP-NPB group, children in MP-PB group still had higher levels of d-dimer and increased inflammatory indicators such as C-reactive protein, procalcitonin, lactate dehydrogenase, and interleukin-6, which were significantly elevated compared with the MP-NPB group. MP-PB showed a higher prevalence of plastic bronchial casts in lower lobes (p = .016) and a dominance of neutrophils in BALF cytology. Additionally, children in the MP-PB group tended to undergo a greater number of bronchoscopies. CONCLUSION: This study identifies key differences in plastic bronchitis in children due to HBoV1 and MP, highlighting HBoV1's milder inflammation in younger kids and MP's link to severe inflammatory and coagulation responses, guiding clinical diagnosis and treatment.

Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021-2022 Bronchiolitis Season in England, Scotland, and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637-29 486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study.

OBJECTIVE: To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit. STUDY DESIGN: In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV-). RESULTS: Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV- children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life. CONCLUSION: RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV- children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Identifying the impact of non-pharmaceutical interventions on RSV transmission in a single-centre observational study.

During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory syncytial virus (RSV), the predominant cause of bronchiolitis. As NPIs were eased, it was speculated that RSV transmission would return with an increase in the severity of bronchiolitis. In a large tertiary hospital, a dramatic reduction in the incidence of bronchiolitis was seen during the COVID-19 pandemic. The easing of NPIs correlated with an increase in RSV transmission particularly in the community; however, there was no evidence of an increase in the severity of bronchiolitis.

Gut and respiratory tract microbiota in children younger than 12 months hospitalized for bronchiolitis compared with healthy children: can we predict the severity and medium-term respiratory outcome?

Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (n = 57, both RSV and non-RSV associated) to a control group (n = 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (R2 = 0.0639, P = 0.006) and NPA (R2 = 0.0803, P = 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in Haemophilus, Streptococcus, and Neisseria) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up. IMPORTANCE: Both the intestinal and respiratory microbiota of children with bronchiolitis, especially those with respiratory syncytial virus infection, are altered and differ from that of healthy children. The microbiota pattern in the acute episode could identify those children who will later have other respiratory episodes in the first year of life. Preventive measures could be adopted for this group of infants.

Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID-19: Results From Four Health Systems, 2015-2023.

BACKGROUND: Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID-19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described. METHODS: Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023. RESULTS: Prior to widespread circulation of SARS-CoV-2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID-19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era. CONCLUSIONS: Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

BACKGROUND: Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. METHODS: We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit. RESULTS: A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001). CONCLUSIONS: This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.

Epidemiological shifts in bronchiolitis patterns and impact of the COVID-19: A two-season comparative study.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection (LRTI) affecting infants and young children. Respiratory syncytial virus (RSV) has historically been the primary causative agent, but other viruses also contribute to the LRTI epidemiology. Recent changes in epidemiology and clinical patterns due to the coronavirus disease 2019 (COVID-19) pandemic have raised concerns. This study aims to analyze the impact of the pandemic on bronchiolitis epidemiology and severity. METHODS: Two consecutive bronchiolitis seasons (October 2021 to March 2022 and October 2022 to March 2023) were compared. Data on viral agents, hospitalization duration, clinical severity, and respiratory support requirements were collected from pediatric patients at San Marco Hospital, University of Catania. RESULTS: In the 2021-2022 season, RSV was the predominant virus (40%), followed by other viruses, with mild clinical outcomes. In the 2022-2023 season, RSV remained prevalent (58.7%), but other viruses, including rhinovirus (RV) and influenza, showed a significant increase (p < .05) in bronchiolitis cases and severity. Notably, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season, contrary to the previous year. CONCLUSION: The COVID-19 pandemic appears to have shifted the epidemiological landscape of bronchiolitis, with a peak incidence in November instead of January/February. Non-RSV viruses (RV, influenza A and B, as well as metapneumovirus) have gained prominence, possibly due to viral competition and reduced pandemic-related restrictions. Traditionally, RSV has been the primary pathogen responsible for most bronchiolitis cases. Nonetheless, the findings of this study indicate a shifting landscape in bronchiolitis etiology, with RSV gradually diminishing in its role. Contrary to the previous year, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season.

Validity of Clinical Severity Scores for Respiratory Syncytial Virus: A Systematic Review.

BACKGROUND: Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score. METHODS: We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated. RESULTS: Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified. CONCLUSIONS: No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets.

Gimap5 promoted RSV degradation through interaction with M6PR.

Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life-threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. RT-qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

The burden and surveillance of RSV disease in young children in Belgium-expert opinion.

Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2-10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5-10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered. CONCLUSION: The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future. WHAT IS KNOWN: • RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated. WHAT IS NEW: • This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system.

Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia.

BACKGROUND: Following a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020. METHOD: At a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020. RESULTS: RSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity. INTERPRETATION: The 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naïve children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.

Inhibition of NF-κB/IL-33/ST2 Axis Ameliorates Acute Bronchiolitis Induced by Respiratory Syncytial Virus.

BACKGROUND/AIM: Bronchiolitis is a common acute lower respiratory tract infectious disease in infants. Respiratory syncytial virus (RSV) infection is one of the main causes. Bronchiolitis can lead to a significant increase in the incidence of asthma in young children, but the mechanism of bronchiolitis transforming into asthma is still unclear. The study was aimed at investigating the role of NF-κB/IL-33/ST2 axis on RSV-induced acute bronchiolitis. METHODS: A total of 40 infants diagnosed with acute bronchiolitis infected by RSV, and 20 normal infants were included in this study. BALB/c mice (6-8 weeks old, 20 ± 1.1 g) were used as study models. Enzyme-linked immunosorbent assay (ELISA), quantitative real time PCR, western blot analysis, immunohistochemical staining, and flow cytometry analysis were performed to examine relevant indicators. RESULTS: IL-33 level was significantly elevated, and Th1/Th2 ratio is imbalance after in infants with acute bronchiolitis. In vivo study, we found that NF-κB/IL-33/ST2 axis is mediated the Th2 cytokine levels and BAL cell number induced by RSV. Acute bronchiolitis induced by RSV in a mouse model is attenuated after inhibition of NF-κB/IL-33/ST2 pathway. Moreover, we also confirmed that macrophages are important sources of IL-33 and are regulated by NF-κB pathway in RSV-induced mice. CONCLUSION: We confirmed that inhibition of NF-κB/IL-33/ST2 axis could attenuate acute bronchiolitis by RSV infected. Our findings not only demonstrate the potential role of IL-33 antibody in attenuating RSV-induced lung damage but also provide a new insight into better prevention of RSV-induced asthma by mediating NF-κB/IL-33/ST2 axis.

Bronchiolitis and SARS-CoV-2.

BACKGROUND: It has been speculated that the SARS-CoV-2 was already widespread in western countries before February 2020. METHODS: We gauged this hypothesis by analysing the nasal swab of infants with either bronchiolitis or a non-infectious disease admitted to the Ospedale Maggiore, Milan (one of the first epicentres of SARS-CoV-2 outbreak in Europe) from November 2019. RESULTS: The SARS-CoV-2 RNA was never detected in 218 infants with bronchiolitis (95 females, median age 4.9 months) and 49 infants (22 females, median age 5.6 months) with a non-infectious disease between November 2019 and February 2020. On the contrary, two infants hospitalised for bronchiolitis between March and April 2020 tested positive for SARS-CoV-2. CONCLUSIONS: This study does not support the hypothesis that SARS-CoV-2 was already circulating among infants before the official outbreak of SARS-CoV-2 infection. However, it shows for the first time that SARS-CoV-2 might cause bronchiolitis requiring hospitalisation.