Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

OBJECTIVE: The 'two-hit' hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. METHODS: We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6-7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported "cough, rattle, or wheeze" and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6-7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. RESULTS: Odds of asthma were higher in sensitized compared to nonsensitized children at age 6-7 years (OR = 14.46; 95% CI 3.99-52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6-7 years in both sensitized (OR = 1.13; 95% CI 1.02-1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11-1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. CONCLUSIONS: Our findings do not support 'two-hit' interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

Impact of Respiratory Viral Infections in Transplant Recipients.

Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population. In this review, we will define the epidemiology and outcomes of RVIs in SOT and HSCT recipients, describe the available assays for diagnosing a suspected RVI, highlight evolving management and vaccination strategies, review the risk of donor derived RVI in SOT recipients, and discuss considerations for delaying transplantation in the presence of an RVI.

Congenital heart surgery outcomes in patients with positive respiratory viral swabs.

OBJECTIVE: To examine whether or not viral positive patients experienced worse outcomes and assess differences in surgical outcomes between viral-positive patients with and without viral symptoms within 30 days of surgery. METHODS: This retrospective study reviewed charts of pediatric patients who underwent congenital heart surgery and routine viral testing at a single institution over a consecutive 3-year period (2017-2019). Patients with a history of heart transplants, pacemaker changes, or implants, and mediastinal washouts were excluded from the study. Surgical outcomes were compared by viral status and viral symptoms, using the Fisher exact and Wilcoxon rank sum tests. RESULTS: Among 1041 patients, 374 patients underwent routine preoperative viral testing, with 107 patients testing positive and 267 testing negative for viral swabs before surgery. There were no significant differences observed in surgical outcomes by viral status, including no differences in mortality. Among the 107 patients with positive viral swabs before surgery, comparisons between 24 patients with viral symptoms and 83 without symptoms within 30 days of surgery detected no significant differences in mortality or complication rates. However, symptomatic versus asymptomatic patients had significantly longer postoperative stay (23.4 vs 13.4 days; P = .02) and intubation time (9.8 vs 4.9 hours; P = .004). CONCLUSIONS: Patients who test positive before congenital heart surgery and are asymptomatic beyond the incubation period may proceed to surgery with no further delay. Patients who are viral positive and symptomatic have a longer postoperative stay and intubation time. A prospective study is needed to assess the importance of routine viral testing.

Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations.

Rationale: Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation.Objectives: To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response.Methods: The STOP2 (Standardized Treatment of Pulmonary Exacerbations II) study was a multicenter randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx. In this ancillary study, participant sputum samples from up to three study visits were tested for respiratory viruses using multiplex polymerase chain reactions. Baselines and treatment-associated changes in mean lung function (percent predicted forced expiratory volume in 1 s), respiratory symptoms (Chronic Respiratory Infection Symptom Score), weight, and C-reactive protein were compared as a function of virus detection. Odds of PEx retreatment within 30 days and future PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively.Results: A total of 1,254 sputum samples from 621 study participants were analyzed. One or more respiratory viruses were detected in sputum samples from 245 participants (39.5%). Virus-positive participants were more likely to be receiving CF transmembrane conductance regulator modulator therapy (45% vs. 34%) and/or chronic azithromycin therapy (54% vs. 44%) and more likely to have received treatment for nontuberculous Mycobacterium infection in the preceding 2 years (7% vs. 3%). At study visit 1, virus-positive participants were more symptomatic (mean Chronic Respiratory Infection Symptom Score, 53.8 vs. 51.1), had evidence of greater systemic inflammation (log10 C-reactive protein concentration, 1.32 log10 mg/L vs. 1.23 log10 mg/L), and had a greater drop in percent predicted forced expiratory volume in 1 second from the prior 6-month baseline (5.8 vs. 3.6). Virus positivity was associated with reduced risk of future PEx (hazard ratio, 0.82; 95% confidence interval, 0.69-0.99; P = 0.034) and longer median time to next PEx (255 d vs. 172 d; P = 0.021) compared with virus negativity.Conclusions: More than one-third of STOP2 participants treated for a PEx had a positive test result for a respiratory virus with more symptomatic initial presentation compared with virus-negative participants, but favorable long-term outcomes. More refined phenotyping of PEx, taking VRIs into account, may aid in optimizing personalized management of PEx.Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Comparative analysis of CRP as a biomarker of the inflammatory response intensity among common viral infections affecting the lungs: COVID-19 versus influenza A, influenza B and respiratory syncytial virus.

Severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) is associated with significant morbidity and mortality. C-reactive protein (CRP) is a useful inflammatory biomarker for patients admitted with an infection. This study aimed to compare CRP level as an indicator of inflammation severity between SARS-CoV-2 and common respiratory viral infections. A cross-sectional study of all adult patients hospitalized in the internal medicine department, geriatric department, or internal intensive care unit between 02/2012 and 06/2021 with laboratory-confirmed respiratory viral infection was performed. SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV) were studied. Patients with laboratory-confirmed concurrent viral or bacterial infections were excluded. Patients with malignancy were also excluded. Age, gender, comorbidities, and CRP level upon admission were compared between groups. Univariate and multivariable analyses were applied. Among 1124 patients, 18.2% had SARS­CoV­2, 48.3% influenza A, 18.9% RSV, and 14.6% influenza B. SARS­CoV­2 patients were significantly younger (median 69.4 vs. ≥ 76 years) and had lower Charlson score (median 3 vs. ≥ 4 in other groups) compared to patients with other viral pathogens. After adjustment for patients' age, gender and comorbidities, SARS­CoV­2 patients had a higher probability (OR = 1.84-2.02, p < 0.01) of having CRP values in the upper quartile (> 117 mg/L) compared to all other viral pathogens while between all others there was no significant difference. To conclude, a higher CRP level upon admission is approximately twice more common among SARS-CoV-2 patients compared to other widespread respiratory viruses which may demonstrate the higher intensity of inflammation caused by SARS-CoV-2.

Impact of RSV test positivity, patient characteristics, and treatment characteristics on the cost of hospitalization for acute bronchiolitis in a French university medical center (2010-2015).

Background: In young children, respiratory syncytial virus (RSV)-related bronchiolitis is typically more severe than other respiratory tract infections, with a greater need for oxygen therapy and respiratory support. Few studies have compared the cost of hospitalization with regard to virological status. The objective of this study was to compare the costs of hospitalization for RSV-positive vs. RSV-negative bronchiolitis in a French university medical center between 2010 and 2015. Methods: The cost models were compared using conventional goodness-of-fit criteria. Covariates included the characteristics of the patients, pre-existing respiratory and non-respiratory comorbidities, superinfections, medical care provided, and the length of stay. Results: RSV was detected in 679 (58.3%) of the 1,164 hospital stays by children under 2 years with virological data. Oxygen therapy and respiratory support were twice as frequent for the RSV-positive cases. The median hospitalization cost was estimated at €3,248.4 (interquartile range: €2,572.1). The cost distribution was positively skewed with a variation coefficient (CV = standard deviation/mean) greater than one (mean = €4,212.9, standard deviation = €5,047, CV = 1.2). In univariate analyses, there was no significant cost difference between the RSV-positive and RSV-negative cases. In the best multivariate model, the significant positive effect of RSV positivity on cost waned after the introduction of medical care variables and the length of stay. The results were sensitive to the specification of the model. Conclusions: It was impossible to firmly conclude that hospitalization costs were higher for the RSV-positive cases.

Viral respiratory infections in a rapidly changing climate: the need to prepare for the next pandemic.

Viral respiratory infections (VRIs) cause seasonal epidemics and pandemics, with their transmission influenced by climate conditions. Despite the risks posed by novel VRIs, the relationships between climate change and VRIs remain poorly understood. In this review, we synthesized existing literature to explore the connections between changes in meteorological conditions, extreme weather events, long-term climate warming, and seasonal outbreaks, epidemics, and pandemics of VRIs from an interdisciplinary perspective. We proposed a comprehensive conceptual framework highlighting the potential biological, socioeconomic, and ecological mechanisms underlying the impact of climate change on VRIs. Our findings suggested that climate change increases the risk of VRI emergence and transmission by affecting the biology of viruses, host susceptibility, human behavior, and environmental conditions of both society and ecosystems. Further interdisciplinary research is needed to address the dual challenge of climate change and pandemics.

Puff, Puff, Don't Pass: harm reduction for cannabis use during a viral respiratory pandemic.

BACKGROUND: Prior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns. METHODS: This cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis. RESULTS: Overall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p < 0.01); less respondents shared most of the time (19.5% before; 11.2% during; p < 0.01) and always during the pandemic (5.2% before; 3.1% during; p < 0.01). After adjusting for covariates, the odds of any sharing during the pandemic for those who reported ≥ weekly cannabis use was 0.53 (95% CI 0.38, 0.75) compared to those who reported ≤ monthly. CONCLUSIONS: Sharing of prepared cannabis and cannabis-related paraphernalia decreased during the COVID-19 pandemic compared to before the pandemic. This finding suggests potential risk mitigation strategies taken by participants for COVID-19 prevention either directly through behavior change or indirectly through adherence to COVID-19 prevention recommendations. Harm reduction messaging around sharing of cannabis during surges of COVID-19 or other respiratory infections may provide benefit in reducing infection among those who use cannabis, especially as cannabis use in the USA continues to increase.

Risk Factors for Respiratory Viral Infections: A Spotlight on Climate Change and Air Pollution.

Climate change has both direct and indirect effects on human health, and some populations are more vulnerable to these effects than others. Viral respiratory infections are most common illnesses in humans, with estimated 17 billion incident infections globally in 2019. Anthropogenic drivers of climate change, chiefly the emission of greenhouse gases and toxic pollutants from burning of fossil fuels, and the consequential changes in temperature, precipitation, and frequency of extreme weather events have been linked with increased susceptibility to viral respiratory infections. Air pollutants like nitrogen dioxide, particulate matter, diesel exhaust particles, and ozone have been shown to impact susceptibility and immune responses to viral infections through various mechanisms, including exaggerated or impaired innate and adaptive immune responses, disruption of the airway epithelial barrier, altered cell surface receptor expression, and impaired cytotoxic function. An estimated 90% of the world's population is exposed to air pollution, making this a topic with high relevance to human health. This review summarizes the available epidemiologic and experimental evidence for an association between climate change, air pollution, and viral respiratory infection.

Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals.

BACKGROUND: The COVID-19 pandemic highlighted the need for early detection of viral infections in symptomatic and asymptomatic individuals to allow for timely clinical management and public health interventions. METHODS: Twenty healthy adults were challenged with an influenza A (H3N2) virus and prospectively monitored from 7 days before through 10 days after inoculation, using wearable electrocardiogram and physical activity sensors. This framework allowed for responses to be accurately referenced to the infection event. For each participant, we trained a semisupervised multivariable anomaly detection model on data acquired before inoculation and used it to classify the postinoculation dataset. RESULTS: Inoculation with this challenge virus was well-tolerated with an infection rate of 85%. With the model classification threshold set so that no alarms were recorded in the 170 healthy days recorded, the algorithm correctly identified 16 of 17 (94%) positive presymptomatic and asymptomatic individuals, on average 58 hours postinoculation and 23 hours before the symptom onset. CONCLUSIONS: The data processing and modeling methodology show promise for the early detection of respiratory illness. The detection algorithm is compatible with data collected from smartwatches using optical techniques but needs to be validated in large heterogeneous cohorts in normal living conditions. Clinical Trials Registration. NCT04204493.

A Versatile Biomimic Nanotemplating Fluidic Assay for Multiplex Quantitative Monitoring of Viral Respiratory Infections and Immune Responses in Saliva and Blood.

The last pandemic exposed critical gaps in monitoring and mitigating the spread of viral respiratory infections at the point-of-need. A cost-effective multiplexed fluidic device (NFluidEX), as a home-test kit analogous to a glucometer, that uses saliva and blood for parallel quantitative detection of viral infection and body's immune response in an automated manner within 11 min is proposed. The technology integrates a versatile biomimetic receptor based on molecularly imprinted polymers in a core-shell structure with nano gold electrodes, a multiplexed fluidic-impedimetric readout, built-in saliva collection/preparation, and smartphone-enabled data acquisition and interpretation. NFluidEX is validated with Influenza A H1N1 and SARS-CoV-2 (original strain and variants of concern), and achieves low detection limit in saliva and blood for the viral proteins and the anti-receptor binding domain (RBD) Immunoglobulin G (IgG) and Immunoglobulin M (IgM), respectively. It is demonstrated that nanoprotrusions of gold electrodes are essential for the fine templating of antibodies and spike proteins during molecular imprinting, and differentiation of IgG and IgM in whole blood. In the clinical setting, NFluidEX achieves 100% sensitivity and 100% specificity by testing 44 COVID-positive and 25 COVID-negative saliva and blood samples on par with the real-time quantitative polymerase chain reaction (p < 0.001, 95% confidence) and the enzyme-linked immunosorbent assay.

Impact of a Rapid Respiratory Pathogen Panel on Antibiotic and Chest Radiography Usage and Hospital Length of Stay in the Pediatric Inpatient Setting.

IntroductionThe objective of this study was to compare the antibiotic initiation rate and duration, hospital length of stay, emergency department (ED) admission rate and chest radiography usage in a pediatric inpatient unit before and after the decentralization of rapid respiratory pathogen panel (RRPP) processing. MethodsThis retrospective cohort study examined antibiotic initiation rates and durations, hospital lengths of stay, ED admission rates, and chest radiography usage from 2 respiratory virus seasons. For the 2014 cohort, RRPPs were processed at a centralized laboratory, and result times averaged 26 hours, whereas for the 2015 cohort, RRPPs were processed on-site with result times averaging 2 hours. Demographic data were collected and demonstrated similar populations. Chi-square testing was used to detect the change of antibiotic initiation rates, ED admission rates, and chest radiography usage after on-site RRPP processing was introduced. Antibiotic duration and hospital length of stay were determined by Wilcoxon rank sum. ResultsThe study population included 94 patients from the 2014 respiratory virus season and 108 patients from the 2015 respiratory virus season. There were no statistically significant differences in gender, ethnicity, or age between the 2 cohorts. Antimicrobial initiation rates during hospital stay decreased from 46% to 27% (p = 0.005). The rate of admission from the ED decreased from 75% to 30% (p < 0.001). There were no statistically significant differences in antibiotic duration, hospital length of stay, or chest radiography usage. ConclusionRapid respiratory pathogen testing is a useful tool that can decrease unnecessary antibiotic initiation and hospital admissions in the pediatric population.

Risk of transmission of respiratory viruses during aerosol-generating medical procedures (AGMPs) revisited in the COVID-19 pandemic: a systematic review.

BACKGROUND: In many jurisdictions healthcare workers (HCWs) are using respirators for aerosol-generating medical procedures (AGMPs) performed on adult and pediatric populations with all suspect/confirmed viral respiratory infections (VRIs). This systematic review assessed the risk of VRIs to HCWs in the presence of AGMPs, the role respirators versus medical/surgical masks have on reducing that risk, and if the risk to HCWs during AGMPs differed when caring for adult or pediatric patient populations. MAIN TEXT: We searched MEDLINE, EMBASE, Cochrane Central, Cochrane SR, CINAHL, COVID-19 specific resources, and MedRxiv for English and French articles from database inception to September 9, 2021. Independent reviewers screened abstracts using pre-defined criteria, reviewed full-text articles, selected relevant studies, abstracted data, and conducted quality assessments of all studies using the ROBINS-I risk of bias tool. Disagreements were resolved by consensus. Thirty-eight studies were included; 23 studies on COVID-19, 10 on SARS, and 5 on MERS/ influenza/other respiratory viruses. Two of the 16 studies which assessed associations found that HCWs were 1.7 to 2.5 times more likely to contract COVID-19 after exposure to AGMPs vs. not exposed to AGMPs. Eight studies reported statistically significant associations for nine specific AGMPs and transmission of SARS to HCWS. Intubation was consistently associated with an increased risk of SARS. HCWs were more likely (OR 2.05, 95% CI 1.2-3.4) to contract human coronaviruses when exposed to an AGMP in one study. There were no reported associations between AGMP exposure and transmission of influenza or in a single study on MERS. There was limited evidence supporting the use of a respirator over a medical/surgical mask during an AGMP to reduce the risk of viral transmission. One study described outcomes of HCWs exposed to a pediatric patient during intubation. CONCLUSION: Exposure to an AGMP may increase the risk of transmission of COVID-19, SARS, and human coronaviruses to HCWs, however the evidence base is heterogenous and prone to confounding, particularly related to COVID-19. There continues to be a significant research gap in the epidemiology of the risk of VRIs among HCWs during AGMPs, particularly for pediatric patients. Further evidence is needed regarding what constitutes an AGMP.

Overnutrition, Nasopharyngeal Pathogenic Bacteria and Proinflammatory Cytokines in Infants with Viral Lower Respiratory Tract Infections.

Background: Little is known about the interaction between the nasopharyngeal bacterial profile and the nutritional status in children. In this study, our main goal was to evaluate the associations between overnutrition and the presence of four potentially pathogenic bacteria in the nasopharynx of infants with viral lower respiratory tract infections (LRTI). In addition, we determined whether changes in the nasopharyngeal bacterial profile were associated with mucosal and serum proinflammatory cytokines and with clinical disease severity. Methods: We enrolled 116 children less than 2 years old hospitalized for viral LRTI during two consecutive respiratory seasons (May 2016 to August 2017); their nutritional status was assessed, and nasopharyngeal and blood samples were obtained. S. aureus, S. pneumoniae, H. influenzae, M. catarrhalis, and respiratory viruses were identified in nasopharyngeal samples by qPCR. Cytokine concentrations were measured in nasopharyngeal and blood samples. Disease severity was assessed by the length of hospitalization and oxygen therapy. Results: Nasopharyngeal pathogenic bacteria were identified in 96.6% of the enrolled children, and 80% of them tested positive for two or more bacteria. The presence and loads of M. catarrhalis was higher (p = 0.001 and p = 0.022, respectively) in children with overnutrition (n = 47) compared with those with normal weights (n = 69). In addition, the detection of >2 bacteria was more frequent in children with overnutrition compared to those with normal weight (p = 0.02). Multivariate regression models showed that the presence and loads of S. pneumoniae and M. catarrhalis were associated with higher concentrations of IL-6 in plasma and TNF-α in mucosal samples in children with overnutrition. Conclusions: The nasopharyngeal profile of young children with overnutrition was characterized by an over representation of pathogenic bacteria and proinflammatory cytokines.

A Review on the Antiviral Activity of Functional Foods Against COVID-19 and Viral Respiratory Tract Infections.

Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.

Advances in the Rapid Diagnostic of Viral Respiratory Tract Infections.

Viral infections are a significant public health problem, primarily due to their high transmission rate, various pathological manifestations, ranging from mild to severe symptoms and subclinical onset. Laboratory diagnostic tests for infectious diseases, with a short enough turnaround time, are promising tools to improve patient care, antiviral therapeutic decisions, and infection prevention. Numerous microbiological molecular and serological diagnostic testing devices have been developed and authorised as benchtop systems, and only a few as rapid miniaturised, fully automated, portable digital platforms. Their successful implementation in virology relies on their performance and impact on patient management. This review describes the current progress and perspectives in developing micro- and nanotechnology-based solutions for rapidly detecting human viral respiratory infectious diseases. It provides a nonexhaustive overview of currently commercially available and under-study diagnostic testing methods and discusses the sampling and viral genetic trends as preanalytical components influencing the results. We describe the clinical performance of tests, focusing on alternatives such as microfluidics-, biosensors-, Internet-of-Things (IoT)-based devices for rapid and accurate viral loads and immunological responses detection. The conclusions highlight the potential impact of the newly developed devices on laboratory diagnostic and clinical outcomes.

Antibiotic Use and Outcomes in Young Children Hospitalized With Uncomplicated Community-Acquired Pneumonia.

Background: We aimed to compare children aged 36 months or younger hospitalized with uncomplicated community-acquired pneumonia (CAP) who are not treated with antibiotics to those treated with antibiotics in terms of clinical features and outcome measures. Methods: Administrative data and medical record review were used to identify patients from 3 to 36 months of age hospitalized from 2011 to 2019 with uncomplicated CAP. Patients were considered treated if they received antibiotics for >2 inpatient days and/or at discharge, and not treated if they received ≤2 inpatient days and no antibiotics at discharge. Untreated patients were compared to treated patients based on demographic features, clinical and laboratory results, and outcomes of interest, including illness severity, length of stay, and 30-day hospital readmissions. Results: Three hundred twenty-two CAP cases were included; 266 (83%) received antibiotics for >48 hours and/or at discharge. Fifty-six patients received ≤2 inpatient days of antibiotics and no antibiotics at discharge; the majority received no inpatient antibiotics. There were no differences between the 2 groups in illness severity, length of stay, or hospital readmissions. The proportion of patients treated with antibiotics decreased from 88% (2011-2013) to 66% during the most recent years studied (2017-2019). Conclusions: There was no difference in outcome of uncomplicated CAP in previously healthy children <36 months of age between those treated and not treated with antibiotics. Additional tools are needed to facilitate identification of viral CAP in young children and decrease unnecessary antibiotic use.

[A new approach to etiotropic therapy ARVI in children].

AIM: Confirmation of the efficacy and safety of the drug riamilovir (Triazavirin®), 100 mg capsules, in children aged 12-17 years with the diagnosis of acute viral respiratory infection (ARVI). MATERIALS AND METHODS: The multicenter study included 269 patients diagnosed with acute viral respiratory infection (ICD-10 code: J00, J02, J02.9, J04, J04.0, J04.1, J04.2, J06, J06.0, J06.9) in the presence of clinical manifestations and confirmation of the etiology of the disease by laboratory tests (PCR method). Patients were included in the study after one of the patient's parents/adoptive parents and the patient signed an informed consent to participate in the study. The interval between the appearance of the first symptoms of the disease and the inclusion of the patient in the study did not exceed 36 hours. RESULTS: As a result of a clinical study, the efficacy and safety of treatment with riamilovir (Triazavirin®) in sick children aged 12-17 years with a diagnosis of ARVI was shown. A decrease in the duration of the disease was shown when using the drug riamilovir (Triazavirin®) compared with the control group. No serious adverse events were detected during the study. CONCLUSION: As a result of the conducted clinical study, the high efficacy, safety and good tolerability of the drug riamilovir in the treatment of children aged 12-17 years with a diagnosis of ARVI was established. It is recommended to use the drug riamilovir in clinical practice as an etiotropic therapy in children aged 12-17 years with a diagnosis of ARVI due to its high efficacy and safety.

Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood.

Background: Genome-wide association studies of asthma have identified associations with variants in type-2 related genes. Also, specific interactions between genetic variants and viral bronchiolitis in the development of asthma has been suggested. Objective: To conduct a gene-based analysis of genetic variants in type 2 cytokine related genes as risk factors for allergic asthma at school age, and further, to study their interaction with specific viral infections in early childhood. Methods: A prospectively investigated cohort of children with previous bronchiolitis and controls came for follow-up at school age. The research visit, blinded to viral exposure, included detailed lung function tests, laboratory investigation, and questionnaires. Allergic asthma was defined as typical symptoms plus objective variable airway obstruction, in addition to laboratory verified atopy (elevated eosinophil count or sensitization to an allergen). Targeted and complete sequencing was performed for nine type 2 cytokine candidate genes: IL4, 5, 13, 25, 33 and 37, IL17RB, CRLF2 and TSLP. Results: At follow-up, there were 109 children with genetic data, 91 with a history of bronchiolitis (46% respiratory syncytial virus, 24% human rhinovirus, 15% human metapneumovirus and 14% mixed viral etiology) and 18 without. The median age was 9.4 years (range 6-13) and 41 (38%) had laboratory verified atopy. Twenty-one children (19%) met the definition of allergic asthma. After adjusting for age, sex and five viral categories, IL33 achieved nominal significance (p = 0.017) for a positive association with allergic asthma development. In the gene-virus interaction analysis, the variant set in IL17RB demonstrated a nominally significant positive interaction with human metapneumovirus infection (p=0.05). Conclusion: The results highlight the multifactorial nature of allergic asthma risk, with both viral infection and inherited genetic variants contributing to increasing risk. Results for IL33 and IL17RB were nominally significant and are potential candidate targets for designing therapeutics and early screening, but these results must be replicated in an independent study.

Do-not-intubate status and COVID-19 mortality in patients admitted to Dutch non-ICU wards.

Mortality from COVID-19 has been particularly high in elderly patients on mechanical ventilation. Treatment outcomes for patients with do-not-intubate (DNI) status are unknown. One hundred patients admitted to the non-ICU ward during the "first wave" were retrospectively analyzed. Mortality rate was 49% in patients with a DNI order. This subgroup was characterized by significantly higher age, more comorbidity, and care dependency. Mortality among DNI patients was three times higher than other patients, but not higher than some of the published mortality rates for elderly mechanically ventilated patients. Advanced care planning is essential in COVID-19 to assist patient autonomy and prevent non-beneficial medical interventions.