Viral Lower Respiratory Infections Research Articles

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated positive correlation with interferon-related protein expression and negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insight into the lower airway and systemic proteome of severe pediatric vLRTI.

Electronic Clinical Decision Support Tools: Strategies to Improve the Management of Lower Respiratory Tract Infections in Low-Resource Settings.

Lower respiratory tract infection (LRTI) is a common reason for hospitalization and antibacterial use globally. There is considerable overlap in the clinical presentation of bacterial and viral LRTIs. Low- or middle-income countries (LMICs) face the dual challenge of appropriately targeting antibacterials for bacterial LRTI while reducing inappropriate antibacterials for viral LRTI. We propose a framework by which an electronic clinical decision support tool (eCDST) for diagnosing LRTI and reducing unnecessary antibacterial use may be developed, validated, and prospectively evaluated in an LMIC. The developed tool would be data driven, low-cost, feasible in the local setting, adaptable based on resource availability, and updated in real time, with prospective assessment to identify its clinical impact. We draw upon our team's recent experience developing an eCDST for LRTI management in Sri Lanka. Publicly sharing such processes and data is valuable, such that we can collectively improve clinical care in LMICs and other settings.

Nirsevimab Effectiveness Against Severe RSV Infection in the Primary Care Setting.

This study assesses the effectiveness of nirsevimab, a monoclonal antibody, in preventing medically attended respiratory syncytial virus-lower respiratory tract infections (RSV-LRTI) in a large primary care network in Spain, in both overall and catch-up infants under ten months of age. The 2023-24 immunization campaign with nirsevimab in Spain targeted all infants born after April 1st, 2023. Those born after October 1st received it at birth in hospitals, while others received it through a catch-up program. The MEDIPRIM network of primary care centers recruited all infants with LRTI for RSV PCR testing and employed a test-negative design (TND) approach to estimate the effectiveness of nirsevimab. The study included 160 infants, 141 (88%) of them received nirsevimab and 128 belonged to the catch-up group (88% received nirsevimab). Overall, RSV was detected in 44 infants (27.5%). Within the catch-up group, 37 (28.9%) were positive for RSV. The overall effectiveness was 75.8% (95% CI: 40.4-92.7), and 80.2% (95% CI: 44.3-95.4) in infants belonging to the catch-up group. This study underscores the effectiveness of nirsevimab in preventing medically attended LRTI in infants in outpatient settings and emphasizes the importance of a catch-up immunization program to reduce the disease burden in primary care.

Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial-viral differentiation.

Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Safety and Pharmacokinetics of Nirsevimab in Immunocompromised Children.

Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged ≤24 months. Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occured through day 151. Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown.

Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner: Cohort Study.

Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. Using a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States. We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites. We were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis. The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment. RR2-10.1101/2023.07.27.23293272.

Passive Immunization Strategies to Prevent Severe Respiratory Syncytial Virus Infection Among Newborns and Young Infants.

Newborns and young infants are at risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection. Passive immunity is the mainstay of infection prevention in this cohort. Transplacental transfer of maternal antibodies provides the newborn with immediate protection from life-threatening infections, however, is dependent upon gestational age, birth weight, mother's age, recent maternal vaccination, maternal nutritional status, maternal immunocompetence and medical conditions, and placental integrity. Efficient transplacental transfer of RSV-neutralizing antibodies have led to the development and approval of maternal RSV immunization for the protection of the newborn. Additionally, administration of RSV-specific antibodies to infants leads to high serum titers of RSV-neutralizing antibodies and further protection from severe disease.

Population Attributable Risk of Wheeze in 2-

There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Prevalence and predictors of antibiotic prescription among patients hospitalized with viral lower respiratory tract infections in Southern Province, Sri Lanka.

Antimicrobial overprescription is common for lower respiratory tract infections (LRTI), as viral and bacterial infections generally present with similar clinical features. Overprescription is associated with downstream antimicrobial resistance. This study aims to identify the prevalence and predictors of antibiotic prescription among patients hospitalized with viral LRTI. A prospective cohort study was conducted among patients aged ≥1 year hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from 2018-2021. Demographic, clinical, and laboratory data were recorded. Nasopharyngeal and blood samples were collected for multiplex polymerase chain reaction testing for 21 respiratory pathogens and procalcitonin (PCT) detection, respectively. Demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests; significant variables (p<0.05) were further included in multivariable logistic regression models. The potential impact of biomarker testing on antibiotic prescription was simulated using standard c-reactive protein (CRP) and PCT cut-offs. Of 1217 patients enrolled, 438 (36.0%) had ≥1 respiratory virus detected, with 48.4% of these patients being male and 30.8% children. Influenza A (39.3%) and human rhinovirus/ enterovirus (28.3%) were most commonly detected. A total of 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics. Among children, neutrophil percentage (median 63.6% vs 47.6%, p = 0.04) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p = 0.003), crepitations/crackles (55.3% vs 21.6%, p<0.001), rhonchi/wheezing (42.9% vs 18.9%, p = 0.005), and chest x-ray opacities (27.4% vs 8.1%, p = 0.01) were associated with antibiotic prescription. Access to CRP and procalcitonin test results could have potentially decreased inappropriate antibiotic prescription in this study by 89.5% and 83.3%, respectively. High proportions of viral detection and antibiotic prescription were observed among a large inpatient cohort with LRTI. Increased access to point-of-care biomarker testing may improve antimicrobial prescription.

Bronchiolitis: Safely Doing Less Is the Next Big Thing

Bronchiolitis is a viral lower respiratory tract infection primarily affecting children younger than 2 years; a common cause of health care encounters, including hospitalization; and a considerable economic burden for health care systems in the United States and worldwide. The American Academy of Pediatrics (AAP) most recently updated its bronchiolitis guideline in 2014 and reaffirmed supportive care as the mainstay of treatment. Despite these recommendations, there is still significant variability in care provided for these children, especially in bronchodilator usage, radiography, and high-flow nasal cannula. Since the 2014 AAP guideline, many pediatric hospitalists have undertaken quality initiatives to improve the adherence to published guidelines, yet a large gap remains between what is recommended and what is practiced. This article presents research on the efficacy of common interventions as well as an introduction to diagnostics and treatments potentially on the horizon. [ Pediatr Ann . 2024;53(6):e223–e228.]

Maternal Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Otherwise Healthy Preterm and Term Infants: A Systematic Review and Meta-analysis.

To date, there is no published, formal assessment of all maternal risk factors for respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) in infants. A systematic literature review and meta-analysis were undertaken to ascertain: What maternal risk factors are associated with an increased risk of RSV-LRTI in infants? The systematic literature review used explicit methods to identify, select and analyze relevant data. PubMed, Embase and the Cochrane Library were searched (November 2022) using terms regarding: (1) RSV/LRTI; (2) risk factors; (3) pregnant/postpartum population. Bayesian meta-analysis compared RSV hospitalization (RSVH) risk in infants born to mothers with or without certain risk factors. A total of 2353 citations were assessed and 20 were included in the final review (10 individual studies; 10 pooled analyses). In 10 studies examining infants (<1 year) without comorbidities (primary outcome), 10 maternal risk factors were associated with RSV-LRTI/RSVH in multivariate analyses. Meta-analysis revealed smoking while pregnant increased infant RSVH risk by 2.01 (95% credible interval: 1.52-2.64) times, while breast-feeding was protective (0.73, 95% credible interval: 0.58-0.90). Risk scoring tools have reported that maternal risk factors contribute between 9% and 21% of an infant's total risk score for RSVH. A greater understanding of maternal risk factors and their relative contribution to infant RSV-LRTI will enable more accurate assessments of the impact of preventive strategies.

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024.

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.

Personalized Infant Risk Prediction for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Requiring Intensive Care Unit Admission.

Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission. We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome. In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]). We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.

Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.

Understanding the use and outcomes of high-flow nasal cannula among infants admitted to Canadian hospitals with bronchiolitis (CanFLO): a protocol for a multicentre, retrospective cohort study

IntroductionBronchiolitis is the most common viral lower respiratory tract infection in children under 2 years of age. Respiratory support with high-flow nasal cannula (HFNC) is increasingly used in this patient...

Evaluation of Etiological Causes and Factors Affect Length of Hospitalization in Neonates Hospitalized with Lower Respiratory Tract Infection.

This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to lower respiratory tract infection (LRTI), to determine the factors that affect the duration of hospitalization, and to determine the underlying microbial factors and evaluate them in the light of the literature. This study evaluated the data of newborns hospitalized with LTRI between 01 October 2022 and 31 March 2023. Demographic characteristics of the patients detected viral agents, duration of hospitalization and risk factors were recorded in the study form. Babies divided viral LRTI and non-viral LRTI, and then compared with each other. Additionally, the facts that might affect the duration of hospitalization were investigated. The study included 57 babies. Viral agent was detected in 50.9% of the babies, the most frequently viral agent was respiratory syncytial virus (RSV) (48.2%). Other viral factors, in order of frequency; Adenovirus, SARS-CoV-2, Influenza A and B. There is no demographic difference between the viral agent positive and negative groups. The patients were evaluated according to length of hospitalization, it was seen that the hospital stay was longer in babies who were found to be viral positive and needed oxygen therapy (p=0.02, p=0.03, respectively). The male gender ratio was higher in the group with longer hospital stays, but this difference was not statistically significant. Although the rate of exclusive breastfeeding was higher in the group with a short hospitalization period, this difference was not statistically significant (p>0.05). RSV is currently the most frequently detected viral agent in lower respiratory tract infections in newborns. The hospital stay of babies diagnosed with RSV is longer than those with non-RSV viral agents. So struggling with RSV is important in preventing lower respiratory tract infections in newborns. It is necessary to develop a vaccine or immunoglobulin application against RSV infection not only for preterm babies but also for all newborn babies.

Changes in clinical, demographic, and outcome patterns of children hospitalized with non-SARS-CoV-2 viral low respiratory tract infections before and during the COVID pandemic in Rome, Italy.

We performed this study aiming to evaluate changes in epidemiology, clinical presentation and outcomes of children hospitalized for viral lower respiratory tract infections (LRTI). We performed a retrospective study of children younger than 18 years of age hospitalized for LRTIs with a positive respiratory viral testing from 2018 to 2022. We compared need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. A total of 523 were included in the analysis. In the pandemic period, the detection of influenza was 95% less likely to occur (odds ratio [OR]: 0.05; 95% confidence interval [95% CI]: 0.02-0.12; p < .001), likewise the detection of adenovirus was 77% less likely to occur (OR: 0.23; 95% CI: 0.10-0.51; p < .001). In the pandemic period, the number of codetections increased from 15.52% in 2018 to 57.25% in 2022, resulting in a significantly increasing trend (p < .001). The odds of transfer to PICU was more than five times greater during the pandemic period (OR: 5.31; 95% CI: 1.78-15.86; p = .003). We found that the pattern of LRTI in children during COVID-19 pandemic significantly changed in terms of etiologies and increased severity.

Admissions for Bronchiolitis at Children’s Hospitals Before and During the COVID-19 Pandemic

The COVID-19 pandemic has been associated with a transient decrease in bronchiolitis hospitalizations compared with prepandemic patterns, but current effects remain unknown. To analyze changes in patterns of bronchiolitis admissions at US children's hospitals during the 2020-2023 bronchiolitis seasons compared with the 2010-2019 seasons. This retrospective cross-sectional study used data from 41 US children's hospitals in the Pediatric Health Information System database. Bronchiolitis has winter-predominant seasonality, so hospitalizations were grouped according to bronchiolitis season (from July through June). This study included all patients aged younger than 2 years admitted with a diagnosis of bronchiolitis between July 1, 2010, and June 30, 2023. Bronchiolitis seasons from July through June between 2010-2011 and 2019-2020 were classified as the prepandemic era, and seasons between 2020-2021 and 2022-2023 were classified as the pandemic era. Data analysis was performed from July 1, 2010, through June 30, 2023. Admission date. The primary outcome was number of hospitalizations for bronchiolitis by season and month. Monthly admission counts from the prepandemic era were transformed into time series and used to train seasonal ensemble forecasting models. Forecasts were compared to monthly admissions during the pandemic era. In this study, there were 400 801 bronchiolitis admissions among 349 609 patients between July 1, 2010, and June 30, 2023. The median patient age was 6 (IQR, 2-12) months; 58.7% were boys and 43.7% were White. Hospitalizations increased gradually during the prepandemic era (median, 29 309 [IQR, 26 196-34 157]), decreased 69.2% (n = 9030) in the 2020-2021 season, and increased 75.3% (n = 51 397) in the 2022-2023 season. Patients in the pandemic era were older than those in the prepandemic era (median, 7 [IQR, 3-14] vs 6 [2-12] months; P < .001). Intensive care unit (ICU) admissions increased from 32.2% (96 245 of 298 535) in the prepandemic era to 36.7% (37 516 of 102 266) in the pandemic era (P < .001). The seasonality of bronchiolitis admissions changed during the pandemic era. Admissions peaked in August 2021 (actual 5036 vs 943 [95% CI, 0-2491] forecasted) and November 2022 (actual 10 120 vs 5268 [95% CI, 3425-7419] forecasted). These findings were unchanged in sensitivity analyses excluding children with complex chronic conditions and excluding repeat admissions. In a sensitivity analysis including all viral lower respiratory tract infections in children aged younger than 5 years, there were 66 767 admissions in 2022-2023 vs 35 623 (31 301-41 002) in the prepandemic era, with the largest increase in children aged 24 to 59 months. The findings of this cross-sectional study suggest that bronchiolitis hospitalizations decreased transiently and then increased markedly during the COVID-19 pandemic era. Patients admitted during the pandemic era were older and were more likely to be admitted to an ICU. These findings suggest that bronchiolitis seasonality has not yet returned to prepandemic patterns, and US hospitals should prepare for the possibility of atypical timing again in 2023.

Severe viral lower respiratory tract infections in Brazilian children: Clinical features of a national cohort

BackgroundThe accurate etiological diagnosis of lower respiratory tract infections (LRTI) is essential for their effective clinical management. The extensive use of molecular methods during the COVID-19 pandemic has enabled massive data acquisition on viral lower respiratory tract infections. The current study aims to identify clinical features associated with eight viral agents among children presenting severe LRTI. Methodsretrospective cohort study of data from the Brazilian Influenza Epidemiological Surveillance Information System. Patients under 20 years-old who had severe LRTI with etiological confirmation through RT-PCR between 2020 and 2022 were included. Binary logistic regressions were used to examine associations between pathogens and symptoms. Results60,657 cases were assessed. The main viral agents detected were Sars-CoV-2 (COV2) (41.2%), Respiratory Syncytial Virus (29.1%), Human Rhinovirus (HRV) (12.1%), and Influenza (FLU) (5.5%). A general mortality rate of 4.3% was observed. The multivariate analysis evidenced that COV2 less likely presented with cough (OR: 0.34; 95%CI: 0.32–0.36), respiratory discomfort (Adjusted Odds Ratio (aOR): 0.61; 95%Confidence Interval (CI): 0.59–0.64), and desaturation (aOR: 0.71; 95%CI: 0.69–0.75). RSV strongly associated with cough (aOR: 2.59; 95%CI: 2.45–2.75) and respiratory discomfort (aOR: 1.54; 95%CI: 1.46–1.62), whereas FLU was linked to fever (aOR: 2.27; 95%CI: 2.06–2.50) and sore throat (aOR: 1.48; 95%CI: 1.34–1.64). ConclusionsThe viral agents responsible for severe LRTI have distinct associations with clinical features in children.