August Wrotek

Introduction and objective: Respiratory syncytial virus is a major cause of lower respiratory tract infections, particularly in children under two years of age. Diagnostic methods include rapid antigen diagnostic tests, which have shown high specificity and variable sensitivity. The aims of this study were to verify the performance of these tests in hospitalised children, and to identify factors influencing the results. Materials and methods: The study enrolled children under two years old who were tested for respiratory syncytial virus using both rapid antigen diagnostic test and a cartridge-based nucleic acid amplification test. The sensitivity, specificity, and positive and negative predictive values of the tests were calculated. The influence of symptoms and fever duration, socioeconomic conditions, presence of siblings, and feeding method were analysed. Results: A total of 164 patients aged 10 days to 24 months (median 2.5 months) were included. Sensitivity reached 75% (95% confidence interval: 67.3–81.7%), specificity – 100% (73.5–100%), positive predictive value – 100%, and negative predictive value – 24% (19.3–29.4%). Lower sensitivity was associated with longer duration of signs/symptoms, with the lowest value obtained in the group with 6–7 days of signs/symptoms – 47.4% (24.5–71.1%), which differed from the 2–3 days group (p = 0.005) and the 4–5 days group (p = 0.016). No association was found between sensitivity and patient age, socioeconomic conditions, presence of siblings, clinical course including fever, or feeding method. None of these factors affected specificity, positive or negative predictive value. Conclusions: The reliability of the rapid antigen diagnostic tests in cases of positive results appears to be high, though negative results should be interpreted with caution. Prolonged duration of signs/symptoms before testing might reduce the level of sensitivity.

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7–100%) versus 93.6% (95% CI 78.6–99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2–100%) and 93.1% (95% CI 77.2–99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (− 2.8, − 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI − 2.83, − 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.

Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in children. An association between air pollution and RSV has received worldwide attention because pollution may contribute to both increased morbidity and disease severity. However, data on this topic are limited,...

Introduction and objective: Bronchiolitis in young children often requires hospitalisation. It is mostly caused by respiratory syncytial virus (RSV) and aetiological factors may be associated with clinical presentation and prognosis. We aimed to compare the epidemiology, clinical features, severity and management of RSV and non-RSV bronchiolitis. Materials and methods: This cross-sectional retrospective study included hospitalised children under 2 years of age. Children with a positive rapid antigen diagnostic test and/or molecular study were included in the RSV group, while those with a negative result were classified as non-RSV bronchiolitis. We compared patient history, clinical presentation, disease severity including passive oxygen therapy, intensive care unit transfer, death, length of hospital stay, presence of complications, oxygen saturation <92%, acidosis, hypercapnia and treatment used. Results: The study included 524 patients (median age 2 months): 462 (88%) RSV and 62 (12%) non-RSV cases. A 7-fold increase in the number of cases was observed between 2010–2011 and 2017–2018. A univariate regression model showed lower odds of family history of atopy (odds ratio, OR = 0.46), higher odds of cough (OR = 4.74), apathy (OR = 2.61), feeding difficulties (OR = 2.03) and vomiting (OR = 3.34) in the RSV group. RSV patients required oxygen therapy (OR = 3.78) and antibiotics (OR = 2.82) more frequently, received inhaled steroid therapy for longer (9 vs. 8 days) and had a higher likelihood of complications (OR = 4.24). A multivariate model showed statistical significance for cough (OR = 6.22), oxygen therapy (OR = 4.43) and complications (OR = 15.95). Conclusions: We observed an increasing trend in bronchiolitis hospitalisations, including RSV bronchiolitis, which was associated with a more severe disease course. No significant clinical features were identified to replace laboratory tests.

Background: Respiratory syncytial virus (RSV) is one of the leading causes of pediatric hospitalizations, mainly in children under 2 years of age. Hospitalization affects the caregivers’ quality of life (QoL). We assessed the caregivers’ QoL during RSV-confirmed hospitalizations of children under 2 years old, identified the most affected QoL dimensions and calculated utilities focusing on the assessment methods and potential confounders. Methods: The caregivers filled out the EQ-5D questionnaire, consisting of a descriptive system (assessing 5 QoL dimensions) and a visual analog scale (EQ VAS). Utility, utility loss and quality-adjusted life years (QALY) loss were calculated, and a concordance between the two systems was assessed. Results: A disturbance in any of the five assessed dimensions was reported by 42% (55 out of 132) of the caregivers, mostly anxiety/depression (37%) and pain/discomfort (17%). The utilities varied between 0.17 and 1 in the descriptive system and 0.33–1 (median 0.86) in the EQ VAS, with a utility loss of 0.14 (IQR: 0.1–0.2). The calculated QALY loss reached a median of 2.45 × 10⁻³ (IQR: 1.37 × 10⁻³–4.56 × 10⁻³) and was not influenced by the patient’s age or the final clinical diagnosis (QALY loss for bronchiolitis: 2.74 × 10⁻³, pneumonia: 1.84 × 10⁻³, bronchitis: 1.78 × 10⁻³, differences statistically insignificant). Only a moderate concordance between the descriptive system and the EQ VAS was seen (Spearman’s rank correlation coefficient = 0.437, p < 0.05), with the latter revealing a higher degree of QoL disturbances. Conclusions: RSV hospitalization influences parental QoL significantly, and anxiety/depression is the most commonly reported issue. Utility impairment scores depend on the assessment method but not on the patient’s age or final diagnosis. Thus, the impact of RSV on caregivers’ QoL cannot be underestimated.

Objective: Concentrations of air pollutants (PM in particular) in Poland are one of the highest in the EU. Although the influence of air pollutants (AP) exposure on increasing risk of viral infections is widely known, there is lack of comprehensive research on relationships between AP exposure and hospitalizations due to respiratory syncytial virus (RSV) infections. Materials and methods: Data from the National Health Fund on RSV LRTIs from 10 consecutive seasons (2010-2019) and official data on daily mean concentrations of PM_2.5, PM₁₀ and NO₂ from 7 Polish cities were used. Patients were included in the analyses based on the final diagnosis of J12.1, J20.5 and J21.0. General Regression Models (GRM) were used to determine the statistically significant effects of single variables with their interactions on health outcomes. Models were evaluated using the adjusted coefficient of determination (R²). Results: 7 cities with the highest number of RSV cases (12,485 hospitalizations in total) were included in the analyses. A substantial part of the RSV hospitalizations in these cities and the analyzed period may have been attributable to the AP. R² in case of multivariate models varied from 0.05 in the city of Walbrzych to 0.31 in case of Gdansk. 10 μg/m³ increase of PM_2.5, PM₁₀ and NO₂ concentration was associated with an average growth in RSV hospitalizations of 0.087-0.16, 0.031-0.087 and 0.04-0.29 respectively. In the univariate model, most significant effects were observed in PM_2.5 and NO₂. Significant association between concentration of these AP and RSV hospitalization was found in 5 out of 7 cities. Conclusions: PM2.5, PM10 and NO2 concentrations explain noticeable part of pediatric RSV hospitalizations.