Effects of Vitamin D Supplementation and Baseline Vitamin D Status on Acute Respiratory Infections and Cathelicidin: A Randomized Controlled Trial.

Background: Vitamin D supplementation may lower the risk of acute respiratory infection (ARI), and the effects may be mediated through the induction of cathelicidin production. Objective: To study the effect of vitamin D supplementation on ARI and cathelicidin concentration in a randomized controlled trial (RCT) and to study the associations between baseline serum 25 hydroxyvitamin D (25(OH)D) and ARIs and cathelicidin concentrations in a 14-week follow-up study. Methods: In the RCT study, the participants were randomized into 2 groups to receive either 20 µg of vitamin D3 or an identical placebo daily. Blood samples were obtained 3 times, at the beginning (study week 0), mid-term (study week 6), and at the end of the study period (study week 14). The follow-up study had 412 voluntary young men from 2 different locations and seasons (January and July). The primary outcomes were the number of ARIs diagnosed and the number of days off because of ARI. Results: In the RCT, vitamin D supplementation had no effect on ARI or days off because of ARI. However, regardless of the group, vitamin D insufficiency (<50 nmol/L) was associated with increased ARI. In the 14-week follow-up study, insufficient serum 25(OH)D at baseline was also associated with increased risk of ARI (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7) and also days-off duty (OR, 2.3; 95% CI, 1.3-4.0) and was inversely associated with cathelicidin concentration (OR, 0.49; 95% CI, .24-.99). Conclusions: Sufficient serum 25(OH)D may be preventive against acute respiratory infection and the preventive effect could be mediated through the induction of cathelicidin production. Clinical Trial Registry number: NCT05014048. https://clinicaltrials.gov/study/NCT05014048?term=NCT05014048&rank=1.

Genetic absence of PD-L1 does not restore CD8+ T cell function during respiratory virus infection and delays virus clearance.

A key mediator of T cell impairment during respiratory virus infection is the inhibitory receptor PD-1. PD-1 is induced on T cells following antigen exposure, whereas proinflammatory cytokines upregulate the ligands PD-L1 and PD-L2. Respiratory virus infection leads to upregulation of PD-L1 on airway epithelial cells, dendritic cells, and alveolar macrophages. However, the role of PD-L1 on different cell types in acute respiratory virus infections is not known. We sought to determine the role of PD-L1 on different cell types in CD8+ T cell impairment. We found that PD-L1-/- mice challenged with human metapneumovirus or influenza showed a similar level of CD8+ T cell impairment compared to wild-type (WT) mice. Moreover, virus clearance was delayed in PD-L1-/- mice compared to WT. CD8+ T cells from PD-L1-deficient mice expressed higher levels of inhibitory receptors both at baseline and after respiratory virus infection. The antibody blockade of PD-L2 failed to restore function to the impaired cells. While reciprocal bone marrow chimeras between WT and PD-L1-/- mice did not restore CD8+ T cell function after the respiratory virus challenge, mice that received the PD-L1-/- bone marrow had higher inhibitory receptor expression on CD8+ cells. This discrepancy in the inhibitory receptor expression suggests that cells of the hematopoietic compartment contribute to T cell impairment on CD8+ T cells.IMPORTANCEThe phenomenon of pulmonary CD8+ T cell impairment with diminished antiviral function occurs during acute respiratory virus infection mediated by Programmed Cell Death-1 (PD-1) signaling. Moreover, PD-1 blockade enhances T cell function to hasten viral clearance. The ligand PD-L1 is expressed in many cell types, but which cells drive lung T cell impairment is not known. We used genetic approaches to determine the contribution of PD-L1 on lung T cell impairment. We found that PD-L2 cannot compensate for the loss of PD-L1, and PD-L1-deficient mice exhibit increased expression of other inhibitory receptors. Bone marrow chimeras between PD-L1-deficient and wild-type mice indicated that hematopoietic PD-L1 expression is associated with inhibitory receptor upregulation and impairment.

Human adenovirus type 4 (HAdV-4) associated acute respiratory tract infection in children & genetic characteristics of HAdV-4 in China: a prospective multicenter study.

BACKGROUND: Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. METHODS: Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. RESULTS: There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. CONCLUSIONS: The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs.

Individual- and community-level predictors of healthcare-seeking behaviour for acute respiratory tract infections among children under five in 29 low-and middle-income countries: a multilevel analysis.

OBJECTIVES: This study aimed to identify the individual- and community-level determinants of mothers' healthcare-seeking behaviour for children under the age of 5 years with acute respiratory infection (ARI) symptoms in low-and middle-income countries (LMICs). STUDY DESIGN: Nationally representative Demographic and Health Survey datasets from 29 LMICs were used. METHODS: The study included 16,893 children aged under 5 years with ARI symptoms in the 2 weeks prior to the survey. A multilevel logistic regression model was used to examine associations between individual- and community-level factors with health-seeking behaviour for ARIs. The adjusted odds ratio (AOR) along with 95% confidence intervals (CIs) were reported as a measure of association. RESULTS: The overall prevalence of healthcare-seeking behaviour for ARIs among children under 5 years in LMICs was 58.83% (95% CI: 58.08, 59.57). Findings showed that mothers with primary or higher education (AOR = 1.20; 95% CI: 1.08, 1.33), and those residing in rich households (AOR = 1.32; 95% CI: 1.18, 1.48), attending antenatal care (ANC) visits (AOR = 1.53; 95% CI: 1.31, 1.79) and delivering at a healthcare facility (AOR = 1.28; 95% CI: 1.16, 1.41) were more likely to seek healthcare for ARIs. A higher level of community maternal education (AOR = 1.44; 95% CI: 1.24, 1.68) was positively associated with seeking healthcare for ARIs, while a higher level of community poverty (AOR = 0.83; 95% CI: 0.72, 0.96) was negatively associated with healthcare seeking for ARIs. CONCLUSIONS: This study revealed that mothers' healthcare-seeking behaviour for ARIs was closely linked to modifiable risk factors, including maternal education, household wealth, use of maternal health services (e.g., ANC), as well as community poverty and literacy levels. Future interventions should consider these modifiable risk factors when developing strategies to improve child health outcomes in LMICs.

Severity of Respiratory Syncytial Virus compared with SARS-CoV-2 and Influenza among hospitalised adults ≥65 years.

INTRODUCTION: Our aim was to estimate the risk of pneumonia, admission to intensive care unit (ICU) or death in individuals ≥65 years old admitted to hospital with RSV, compared to influenza or COVID-19. METHODS: We included hospitalised patients from Severe Acute Respiratory Infection Surveillance in Spain between 2021-2024, aged ≥65 years, laboratory confirmed for RSV, influenza or SARS-CoV-2. Using a binomial regression with logarithmic link, we estimated the relative risk (RR) of pneumonia, ICU admission and in-hospital mortality, in patients with RSV compared to influenza or SARS-CoV-2, adjusting for age, sex, season and comorbidities. We stratified the estimates by vaccination status for influenza or SARS-CoV2. RESULTS: Among patients unvaccinated for influenza or SARS-CoV-2, those with RSV had similar or lower risk of pneumonia [vs. influenza: RR=0.91 (95% Confidence Interval: 0.72-1.16); vs. SARS-CoV-2: 0.81(0.67-0.98)], ICU admission [vs. influenza: 0.93(0.41-2.08); vs. SARS-CoV-2: 1.10 (0.61-1.99)] and mortality [vs. influenza: 0.64(0.32-1.28); vs. SARS-CoV-2: 0.56(0.30-1.04)]. Among the vaccinated, results were largely similar except for a higher risk of ICU admission with RSV [vs. influenza: 2.13(1.16-3.89); vs. SARS-CoV-2: 1.83 (1.02-3.28)] CONCLUSIONS: RSV presented similar or lower intrinsic severity than influenza or SARS-CoV2. Among vaccinated patients, RSV was associated to higher ICU-admission, suggesting the potential for preventive RSV vaccination.

Human metapneumovirus (hMPV): an associated etiology of severe acute respiratory infection in children of Eastern Uttar Pradesh, India.

Acute respiratory infections (ARIs) are a serious public health concern across the world, causing considerable morbidity and mortality. Every year, around 13 million children under the age of five die. Approximately 95% of them are from developing nations, and ARIs are responsible for one-third of all deaths. Human Metapneumovirus (hMPV) is one of the causative agents associated with respiratory tract infections. There is lack of information about hMPV from the eastern region of Uttar Pradesh. At Indian Council of Medical Research- Regional Medical Research Centre, Gorakhpur (ICMR-RMRC, Gorakhpur) in Uttar Pradesh, India; we tested respiratory pathogens in under-five patients presenting with ARI and severe acute respiratory illness (SARI) through semi nested PCR. A total of 100 nasal and throat specimens were collected from the outdoor and indoor patient Departments (OPD) and (IPD) of Department of Paediatrics, BRD Medical College, Gorakhpur during February to April 2022. Out of 100 enrolled paediatric patients, 4(4%) were found to be hMPV positive. Among the patients who tested positive for hMPV, 25%(1/4) unfortunately died. The phylogenetic analysis of hMPV showed the close resemblance with the clade of Singapore and USA hMPV isolates. The study underlines the importance of hMPV as the cause of acute respiratory infections in children and the highlight the need for routine testing for this virus in laboratories. Further more comprehensive detailed study on various aspects of hMPV in this area is needed.

Initial assessment and management of adults with suspected acute respiratory infection: a rapid evidence synthesis of reviews and cost-effectiveness studies.

Background: This work was undertaken to inform a National Institute for Health and Care Excellence guideline on the initial assessment of adults with suspected acute respiratory infection. Objective: To undertake a rapid evidence synthesis of systematic reviews and cost-effectiveness studies of signs, symptoms and early warning scores for the initial assessment of adults with suspected acute respiratory infection. Methods: MEDLINE, EMBASE and Cochrane Database of Systematic Reviews were searched for systematic reviews and MEDLINE, EMBASE, EconLit and National Health Service Economic Evaluation Database were searched for cost-effectiveness studies in May 2023. References of relevant studies were checked. Clinical outcomes of interest included escalation of care, antibiotic/antiviral use, time to resolution of symptoms, mortality and health-related quality of life. Risk of bias was assessed using the Risk of Bias in Systematic Reviews tool or the National Institute for Health and Care Excellence economic evaluations checklist. Results were summarised using narrative synthesis. Results: Nine systematic reviews and one cost-effectiveness study met eligibility criteria. Seven reviews assessed several early warning scores for patients with community- acquired pneumonia, one assessed early warning scores for nursing home-acquired pneumonia and one assessed individual signs/symptoms and the Centor score for patients with sore throat symptoms; all in face-to-face settings. Two good-quality reviews concluded that further research is needed to validate the CRB-65 in primary care/community settings. One also concluded that further research is needed on the Pneumonia Severity Index in community settings; however, the Pneumonia Severity Index requires data from tests not routinely conducted in community settings. One good-quality review concluded that National Early Warning Score appears to be useful in an emergency department/acute medical setting. One review (unclear quality) concluded that the Pneumonia Severity Index and CURB-65 appear useful in an emergency department setting. Two poor-quality reviews concluded that early warning scores can support clinical judgement and one poor-quality review found numerous problems with using early warning scores in a nursing home setting. A good-quality review concluded that individual signs and symptoms have a modest ability to diagnose streptococcal pharyngitis, and that the Centor score can enhance appropriate prescribing of antibiotics. The cost-effectiveness study assessed clinical scores and rapid antigen detection tests for sore throat, compared to delayed antibiotic prescribing. The study concluded that the clinical score is a cost-effective approach when compared to delayed prescribing and rapid antigen testing. Conclusions: Several early warning scores have been evaluated in adults with suspected acute respiratory infection, mainly the CRB-65, CURB-65 and Pneumonia Severity Index in patients with community-acquired pneumonia. The evidence was insufficient to determine what triage strategies avoid serious illness. Some early warning scores (CURB-65, Pneumonia Severity Index and National Early Warning Score) appear to be useful in an emergency department/acute medical setting; however, further research is required to validate the CRB-65 and Pneumonia Severity Index in primary care/community settings. The economic evidence indicated that clinical scores may be a cost-effective approach to triage patients compared with delayed prescribing. Future work and limitations: Only systematic reviews were eligible for inclusion in the synthesis of clinical evidence. There was a great deal of overlap in the primary studies included in the reviews, many of which had significant limitations. No studies were undertaken in remote settings (e.g. NHS 111). Only one cost-effectiveness study was identified, with limited applicability to the review question. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159945.

Acute respiratory infections, such as cold and flu, are common and can be caused by viruses or bacteria. People with symptoms of acute respiratory infection often go to their general practitioner, who may advise them to stay at home (with or without antibiotics or antivirals) or might refer them to hospital if the infection is serious. Doctors assess the patient's symptoms or may use a tool called an 'early warning score' to judge whether the infection is serious. A systematic review is a research method where all relevant studies assessing a specific question are found and summarised. We aimed to summarise all systematic reviews and cost-effectiveness studies that assessed signs, symptoms and 'early warning scores' in adults with suspected acute respiratory infections in the community (i.e. not hospitalised patients). We found nine systematic reviews and one cost-effectiveness study. Several different early warning scores for acute respiratory infection have been assessed in systematic reviews. Seven of the reviews assessed early warning scores in patients with community-acquired pneumonia. Good-quality reviews concluded that further research is needed to see how useful the 'CRB-65' and 'Pneumonia Severity Index' early warning scores are for assessing pneumonia severity in the community. Another good-quality review concluded that the 'National Early Warning Score' early warning score appears to be useful in an emergency department setting. A good-quality review found that individual symptoms are not very reliable for diagnosing pharyngitis caused by streptococcal bacteria in patients with sore throat; the review also found that the 'Centor score' can help doctors decide whether to prescribe antibiotics for pharyngitis. The cost-effectiveness study assessed clinical scores and rapid antigen detection tests (which test for substances that increase in our blood when we have certain infections) in patients with sore throat, and found that clinical scores may be cost-effective compared to delaying prescribing antibiotics.

Evaluation of the influenza-like illness case definition and the acute respiratory infection case definition in the diagnosis of influenza and COVID-19 in healthcare personnel.

BACKGROUND: To evaluate the influenza-like illness (ILI) and acute respiratory infection (ARI) case definitions in the diagnosis of COVID-19 and influenza in healthcare personnel (HCP). METHODS: We followed a cohort of 5752 HCP from November 2022 to May 2023. Symptomatic HCP were tested for SARS-CoV-2 and influenza by real-time PCR and/or rapid antigen detection test. ILI was defined as the sudden onset of ≥1 systemic symptom and ≥1 respiratory symptom. ARI was defined as the sudden onset of ≥1 respiratory symptom. Patients with respiratory symptoms were grouped either as ILI or as ARI based on the presence of fever, malaise, headache and/or myalgia. RESULTS: Overall, 466 ILI cases and 383 ARI cases occurred. HCP with ILI had an adjusted odds ratio (aOR) of 22.05 [95% confidence interval (CI): 6.23-78.04] to be diagnosed with influenza. HCP with ARI had an aOR of 2.70 (95% CI: 1.88-3.88) to be diagnosed with COVID-19. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ILI for influenza were 96.6%, 49.9%, 18.2%, and 99.2%, respectively. The sensitivity, specificity, PPV, and NPV of ARI for COVID-19 were 51.7%, 73.6%, 84.9%, and 34.8%, respectively. ILI and ARI had an overall correct classification rate of 89.6% and 74.1%, respectively. CONCLUSION: Our findings support the use of both ILI and ARI case definitions in the diagnosis of influenza and COVID-19 in HCP.

Effects of the Local Environment and Nutritional Status on the Incidence of Acute Respiratory Infections Among Children Under 5 Years Old in Indonesia.

Objectives: This study aimed to map the incidence of acute respiratory infections (ARIs) among under-5 children in Indonesia, address the triple burden of malnutrition, and analyze the impact of malnutrition on ARIs, taking into account the environmental and wealth disparities in Indonesia. Methods: This study utilized an ecological design, analyzing aggregate data from the Indonesia Nutrition Survey, 2022. It encompassed 33 provinces and 486 districts/cities, involving a total of 334,848 children under 5 years of age. Partial least squares structural equation modeling was employed to investigate the relationships among wealth, environment, malnutrition (stunting, wasting, and underweight), and ARIs. Results: The proportion of ARI cases in Indonesia was generally concentrated in central Sumatra, the western and eastern parts of Java, and eastern Papua. In contrast, the northern part of Sumatra, central Kalimantan, central Sulawesi, and central Papua had a higher proportion of malnutrition cases compared to other regions. Negative associations were found between malnutrition and ARIs (path coefficient = -0.072, p<0.01) and between wealth and environment (path coefficient = -0.633, p<0.001), malnutrition (path coefficient = -0.399, p<0.001), and ARIs (path coefficient = -0.918, p<0.001). Conclusions: An increasing wealth index is expected to contribute to reducing ARIs, malnutrition and environmental burdens in the future. This study emphasizes the necessity for focused strategies that address both immediate health challenges and the underlying socioeconomic determinants to improve child health outcomes in the Indonesian context.

Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a systematic review, dose-response and pairwise meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.

Investigating neighbourhood environmental risk factors associated with childhood acute respiratory infection symptoms in Ethiopia mixed effect and multilevel logistic regression analysis based on EDHS 2016.

Background: Acute respiratory infection is an infectious illness caused by acute viral or bacterial infection. According to a 2018 WHO report, exposures to indoor and ambient air environmental pollution were contributing factors to a higher risk of respiratory problems following 7 million deaths of children under five globally. Housing conditions such as wall material, roof type, kitchen location, sanitation condition, and cooking fuel type are household-level predictors of acute respiratory disease among children under five years of age. Method: This research used EDHS-2016 secondary data, which are nationally representative. The data collection period was from January 18, 2016, to June 27, 2016. Among the 16,650 total surveys, 10,006 households that had children below 5 years of age. The outcome variable for this study was acute respiratory infection symptoms. Analyses were performed using STATA Version 17.1. The data were weighted before performing analysis to reinstate the representativeness of the sample. In the bivariable analysis, a p value <0.2 was used to screen for multivariable. Multicollinearity was checked using the variance inflation factor. Then, a multilevel multivariable regression model was used in this study for the analysis of acute respiratory infection symptoms and possible predictor variables. Variables with a p value <0.05 in multivariable regression analysis were considered statistically significant predictors. Results: Most (95.00%) households commonly used solid fuel for cooking, and household main construction materials: 81.44 and 91.03% of floors and walls of households were constructed with unprocessed natural materials, respectively. The prevalence of acute respiratory infection symptoms among children under five years of age was 7.955% (7.397, 8.551%). The findings indicated that acute respiratory infection symptoms among children under five years of age were significantly linked with the age of the children, diarrhea status, residence, region, fuel type, stool disposal, wall material, and floor material. Conclusion: Interventions should target modifiable factors such as proper stool disposal of the youngest child, informing the health effects of poor housing conditions such as improving wall and floor construction material to reduce acute respiratory infection symptoms among children under five years of age.

Interpretable prediction of acute respiratory infection disease among under-five children in Ethiopia using ensemble machine learning and Shapley additive explanations (SHAP).

Background: Although the prevalence of childhood illnesses has significantly decreased, acute respiratory infections continue to be the leading cause of death and disease among children in low- and middle-income countries. Seven percent of children under five experienced symptoms in the two weeks preceding the Ethiopian demographic and health survey. Hence, this study aimed to identify interpretable predicting factors of acute respiratory infection disease among under-five children in Ethiopia using machine learning analysis techniques. Methods: Secondary data analysis was performed using 2016 Ethiopian demographic and health survey data. Data were extracted using STATA and imported into Jupyter Notebook for further analysis. The presence of acute respiratory infection in a child under the age of 5 was the outcome variable, categorized as yes and no. Five ensemble boosting machine learning algorithms such as adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), Gradient Boost, CatBoost, and light gradient-boosting machine (LightGBM) were employed on a total sample of 10,641 children under the age of 5. The Shapley additive explanations technique was used to identify the important features and effects of each feature driving the prediction. Results: The XGBoost model achieved an accuracy of 79.3%, an F1 score of 78.4%, a recall of 78.3%, a precision of 81.7%, and a receiver operating curve area under the curve of 86.1% after model optimization. Child age (month), history of diarrhea, number of living children, duration of breastfeeding, and mother's occupation were the top predicting factors of acute respiratory infection among children under the age of 5 in Ethiopia. Conclusion: The XGBoost classifier was the best predictive model with improved performance, and predicting factors of acute respiratory infection were identified with the help of the Shapely additive explanation. The findings of this study can help policymakers and stakeholders understand the decision-making process for acute respiratory infection prevention among under-five children in Ethiopia.

Weekly Vitamin D Supplementation to Prevent Acute Respiratory Infections in Young Children at Different Latitudes: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of weekly vitamin D supplementation in reducing the number of acute respiratory infections (ARI) in preschool children. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial in 303 children aged 1.5-3.5 years from 2014 to 2105 in 3 Chilean cities at different latitudes: Santiago (33°S, n = 101), Talcahuano (37°S, n = 103), and Punta Arenas (53°S, n = 99). Participants were allocated (1:1:1) to receive placebo, cholecalciferol (vitamin D3 (VD3)) 5600 IU/week (low-dose), or 11 200 IU/week (high-dose) for 6 months. Primary outcome was parent-reported number of ARI; secondary outcomes included number of ARI hospitalizations, change of serum 25-hydroxyvitamin D (25(OH)D) and LL-37/cathelicidin levels, and adverse events. RESULTS: The mean age of participants was 26 ± 6 months; 45% were female. Baseline 25(OH)D was 24.9 ± 6.1 ng/ml, with 23% having 25(OH)D <20 ng/ml. No significant baseline clinical or laboratory differences were observed among groups. Overall, 64% (n = 194) completed study participation, without baseline differences between subjects lost to follow-up vs those completing participation or differences in completion rates across groups. After 6 months, a dose-dependent increase in serum 25(OH)D was observed from the VD3 intervention (P < .001), with a higher proportion of subjects ending the trial with 25(OH)D <20 ng/ml in the placebo group (30.8%) vs the low-dose (7.4%) and high-dose groups (5.1%). However, no group differences were observed in number of ARI (P = .85), ARI hospitalizations (P = .20), LL-37/cathelicidin change (P = .30), or adverse events (P = .41). CONCLUSIONS: While weekly VD3 supplementation, in doses equivalent to 800 IU and 1600 IU daily, was associated with improved 25(OH)D levels in preschoolers, we did not find a reduced number of ARI in this sample.

Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES:  Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares the clinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. METHODS:  This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. RESULTS:  From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0), shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. CONCLUSIONS: Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Use of proxy indicators for automated surveillance of severe acute respiratory infection, the Netherlands, 2017 to 2023: a proof-of-concept study.

BackgroundEffective pandemic preparedness requires robust severe acute respiratory infection (SARI) surveillance. However, identifying SARI patients based on symptoms is time-consuming. Using the number of reverse transcription (RT)-PCR tests or contact and droplet precaution labels as a proxy for SARI could accurately reflect the epidemiology of patients presenting with SARI.AimWe aimed to compare the number of RT-PCR tests, contact and droplet precaution labels and SARI-related International Classification of Disease (ICD)-10 codes and evaluate their use as surveillance indicators.MethodsPatients from all age groups hospitalised at Leiden University Medical Center between 1 January 2017 up to and including 30 April 2023 were eligible for inclusion. We used a clinical data collection tool to extract data from electronic medical records. For each surveillance indicator, we plotted the absolute count for each week, the incidence proportion per week and the correlation between the three surveillance indicators.ResultsWe included 117,404 hospital admissions. The three surveillance indicators generally followed a similar pattern before and during the COVID-19 pandemic. The correlation was highest between contact and droplet precaution labels and ICD-10 diagnostic codes (Pearson correlation coefficient: 0.84). There was a strong increase in the number of RT-PCR tests after the start of the COVID-19 pandemic.DiscussionAll three surveillance indicators have advantages and disadvantages. ICD-10 diagnostic codes are suitable but are subject to reporting delays. Contact and droplet precaution labels are a feasible option for automated SARI surveillance, since these reflect trends in SARI incidence and may be available real-time.

Post-discharge mortality among patients hospitalised with severe acute respiratory infection, Bangladesh, 2012-2019: a prospective observational study.

Background: Enhancing outcomes post-hospitalisation requires an understanding of predictive factors for adverse events. This study aimed to estimate post-discharge mortality rates among patients with severe acute respiratory infection (SARI) in Bangladesh, identify associated factors, and document reported causes of death. Methods: From January 2012 to December 2019, we conducted follow-up calls to patients or their families 30 days after discharge to assess the status of patients with SARI. Proportions of deaths within 30 days of discharge were estimated, and a comparative analysis of demographics, clinical characteristics, and influenza illness between decedents and survivors was performed using multivariable Cox regression models. Findings: Among 23,360 patients with SARI (median age: 20 years, IQR: 1.5-48, 65% male), 351 (1.5%) died during hospitalisation. Of 23,009 patients alive at discharge, 20,044 (87%) were followed, with 633 (3.2%) deaths within 30 days of discharge. In children (<18 years), difficulty breathing (adjusted hazard ratio [aHR] 1.8; 95% CI 1.1-3.0), longer hospital stay (aHR 1.1; 95% CI 1.1-1.1), and heart diseases (aHR 8.5; 95% CI 3.2-23.1) were associated with higher post-discharge death risk. Among adults (≥18 years), difficulty breathing (aHR 2.3; 95% CI 1.7-3.0), chronic obstructive pulmonary disease (aHR 1.7; 95% CI 1.4-2.2), and intensive care unit admission (aHR 5.2; 95% CI 1.9-14.0) were linked to elevated post-discharge death risk. Influenza virus was detected in 13% (46/351) of in-hospital SARI deaths and 10% (65/633) of post-discharge SARI deaths. Interpretation: Nearly one in twenty patients with SARI died during hospitalisation or within 1 month of discharge, with two-thirds of deaths occurring post-discharge. Seasonal influenza vaccination is recommended to mitigate influenza-associated mortality. To enhance post-discharge outcomes, hospitals should consider developing safe-discharge algorithms, reinforcing post-discharge care plans, and establishing outpatient monitoring for recently discharged patients. Funding: Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA [U01GH002259].

Real-Time Enterovirus D68 Outbreak Detection through Hospital Surveillance of Severe Acute Respiratory Infection, Senegal, 2023.

In December 2023, we observed through hospital-based surveillance a severe outbreak of enterovirus D68 infection in pediatric inpatients in Dakar, Senegal. Molecular characterization revealed that subclade B3, the dominant lineage in outbreaks worldwide, was responsible for the outbreak. Enhanced surveillance in inpatient settings, including among patients with neurologic illnesses, is needed.

Factors of acute respiratory infection among under-five children across sub-Saharan African countries using machine learning approaches.

Symptoms of Acute Respiratory infections (ARIs) among under-five children are a global health challenge. We aimed to train and evaluate ten machine learning (ML) classification approaches in predicting symptoms of ARIs reported by mothers among children younger than 5 years in sub-Saharan African (sSA) countries. We used the most recent (2012-2022) nationally representative Demographic and Health Surveys data of 33 sSA countries. The air pollution covariates such as global annual surface particulate matter (PM 2.5) and the nitrogen dioxide available in the form of raster images were obtained from the National Aeronautics and Space Administration (NASA). The MLA was used for predicting the symptoms of ARIs among under-five children. We randomly split the dataset into two, 80% was used to train the model, and the remaining 20% was used to test the trained model. Model performance was evaluated using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve. A total of 327,507 under-five children were included in the study. About 7.10, 4.19, 20.61, and 21.02% of children reported symptoms of ARI, Severe ARI, cough, and fever in the 2 weeks preceding the survey years respectively. The prevalence of ARI was highest in Mozambique (15.3%), Uganda (15.05%), Togo (14.27%), and Namibia (13.65%,), whereas Uganda (40.10%), Burundi (38.18%), Zimbabwe (36.95%), and Namibia (31.2%) had the highest prevalence of cough. The results of the random forest plot revealed that spatial locations (longitude, latitude), particulate matter, land surface temperature, nitrogen dioxide, and the number of cattle in the houses are the most important features in predicting the diagnosis of symptoms of ARIs among under-five children in sSA. The RF algorithm was selected as the best ML model (AUC = 0.77, Accuracy = 0.72) to predict the symptoms of ARIs among children under five. The MLA performed well in predicting the symptoms of ARIs and associated predictors among under-five children across the sSA countries. Random forest MLA was identified as the best classifier to be employed for the prediction of the symptoms of ARI among under-five children.

SARS-CoV-2 infection decreases cardiorespiratory fitness and time-trial performance even two months after returning to regular training - Insights from a longitudinal case series of well-trained kayak athletes.

Objective: The aims of this study were to examine the effect of SARS-CoV-2 infection on cardiorespiratory fitness (CRF) and time-trial performance in vaccinated well-trained young kayak athletes. Methods: This is a longitudinal observational study. Sixteen (7 male, 9 female) vaccinated kayakers underwent body composition assessment, maximal graded exercise test, and 1000-m time-trial tests 21.9 ± 1.7 days before and 66.0 ± 2.2 days after the SARS-CoV-2 infection. The perception of training load was quantified with Borg's CR-10 scale before and after the infection return to sport period. Results: There were significant decreases in peak oxygen uptake (-9.7 %; effect size [ES] = 1.38), peak oxygen pulse (-5.7 %; ES = 0.96), and peak heart rate (-1.9 %; ES = 0.61). Peak minute ventilation, and minute ventilation/carbon dioxide production slope were unchanged after infection compared to the pre-infection values. In the entire 1000-m, the impaired tendencies were found in completion time, mean power, and mean speed (-2.4 to 1.2 %; small ESs = -0.40 to 0.47) as well as significant changes in stroke rate and stroke length (-4.5 to 3.7 %; ESs = -0.60 to 0.73). Conclusion: SARS-CoV-2 infection decreased CRF and time-trial performance even two months after return to regular training in vaccinated athletes.