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Respiratory syncytial virus (RSV) is becoming increasingly recognized as a serious threat to vulnerable population subgroups. This study describes the statistical analysis plan for a retrospective cohort study of adults hospitalized for acute respiratory infection (ARI) to estimate the population burden of RSV especially for groups such as the elderly, pregnant women and solid organ transplant patients. Disease burden estimates are essential for setting vaccine policy, e.g., should RSV vaccine become available, burden estimates may inform recommendations to prioritize certain high-risk groups. The study population is residents of Allegheny County, Pennsylvania ≥18 years of age who were hospitalized in Pennsylvania during the period September 1, 2015-August 31, 2018. Data sources will include U.S. Census, Pennsylvania Health Care Cost Containment Council (PHC4) and the electronic medical record for the health system to which the hospitals belong. The algorithm involves: 1) ARI-associated hospitalizations in PHC4 data; 2) adjustment for ARI hospitalizations among county residents but admitted to hospitals outside the county; and 3) RSV detections from respiratory viral panels. Key sensitivity analyses will adjust for undertesting for viruses in the fall and spring quarters. The results will be population-based estimates, stratified by age and risk groups. Adjusting hospitalization data using a multiplier method is a simple means to estimate the impact of RSV in a given area. This algorithm can be applied to other health systems and localities to estimate RSV and other respiratory pathogen burden in adults, to estimate burden following introduction of RSV vaccine and to make cost-effectiveness estimates.

Here we review the existing evidence of animal alphacoronaviruses ( Alphacoronavirus 1 species ) circulating in human patients with acute respiratory illness. Thus far, the viruses similar to canine, feline and porcine alphacoronaviruses (including the most recent CCoV-HuPn-2018 and HuCCoV_Z19) have been detected in humans in Haiti, Malaysia, Thailand, and USA. The available data suggest that these viruses emerged in different geographic locations independently and have circulated in humans for at least 20 years. Additional studies are needed to investigate their prevalence and disease impact.

Background: Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses., Methods: We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1-4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS)., Results: Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11-2.34]), RSV (aOR = 4.48; 95% CI = [2.81-7.14]), HMPV (aOR = 3.39; 95% CI = [1.69-6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14-3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS., Conclusions: HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Respiratory syncytial virus (RSV) infections are the leading cause of hospitalization in young children. We assessed the epidemiology, severity, clinical characteristics, molecular profile and genetic factors of RSV infections compared to acute respiratory illness (ARI) caused by other respiratory viruses., Methods: Prospective cohort study was conducted from 2017 to 2018 with children under 2 years old hospitalized with ARI. Detection of respiratory viruses was carried out using RT-PCR. RSVs were genotyped via nucleotide sequencing, and host interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) were determined using SNP TaqMan® Genotyping Assays., Results: A total of 468 children were included; 288 (61.5%) had an infection by a single virus: 202 (70.1%) cases by RSV followed by rhinovirus 36 (12.5%) and influenza 16 (5.6%). Of the RSV cases, 36% were genotyped with a higher prevalence of RSV B (62.1%). The RSV group presented median age of 2.7 months (1.6-6.8), higher frequency in: intensive care unit admission (p = 0.004), mechanical ventilation use (p = 0.018), wheezing (p < 0.001), antimicrobial use (p < 0.001) and low oxygen saturation (p < 0.001). Prematurity (27.2%) was the most frequent comorbidity. RSV patients without comorbidities demonstrated a higher frequency in the combination of IL28B rs12979860 CT/IL28B rs8099917 TG and IL28B rs12979860 TT/IL28B rs8099917 TT genotypes. Viral coinfection was detected in 27 (5.7%) children, with the most frequent being RSV and rhinovirus (14.2%)., Conclusions: This study highlighted the burden of RSV infection in children under 2 years of age, without comorbidities, with a higher need for pediatric ICU admission. Some IL28B allele combinations had a significant association with RSV frequency of infections., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ABSTRACT Associations between the severity of respiratory signs and symptoms and the respiratory viruses identified in 214 Japanese children with acute respiratory illness (ARI) enrolled between January and December 2012 were studied. Respiratory rate, wheezing, cyanosis, and the use of accessory muscles were used as indices of respiratory severity and phylogenetic analysis of the viruses identified in these children was performed. Respiratory viruses such as respiratory syncytial virus (RSV), human rhinovirus (HRV), human parainfluenza virus (HPIV), and human metapneumovirus (HMPV) were prevalent, being detected in approximately 70% of the patients (151/214 patients). Co-detection of viruses occurred in about 9% of patients. RSV was identified more frequently in cases scored as moderate/severe than in those scored as mild ( P < 0.05). Severity scores of patients with RSV were significantly higher than those of cases with HPIV. Moreover, severity scores in patients with mild disease and co-detections were higher than in those in whom only HPIV or adenovirus was detected. Phylogenetic analysis showed that many genotypes of HRV-A and -C with wide genetic divergence were associated with acute respiratory illness (ARI). On the other hand, only a limited number of genotypes of RSV were associated with ARI. HPIV and HMPV were associated with ARI at similar frequencies. These results suggest that different respiratory viruses with unique genetic characteristics can be found in patients with mild to severe ARI. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory illness, a leading cause of cough in children, accounts for a substantial proportion of childhood morbidity and mortality worldwide. In some children acute cough progresses to chronic cough (>4 weeks duration), impacting on morbidity and decreasing quality of life. Despite the importance of chronic cough as a cause of substantial childhood morbidity and associated economic, family and social costs, data on the prevalence, predictors, aetiology and natural history of the symptom are scarce. This study aims to comprehensively describe the epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children presenting to a tertiary paediatric emergency department. Methods/design: A prospective cohort study of children aged <15 years attending the Royal Children's Hospital Emergency Department, Brisbane, for a respiratory illness that includes parent reported cough (wet or dry) as a symptom. The primary objective is to determine the prevalence and predictors of chronic cough (=4 weeks duration) post presentation with acute respiratory illness. Demographic, epidemiological, risk factor, microbiological and clinical data are completed at enrolment. Subjects complete daily cough dairies and weekly follow-up contacts for 28(±3) days to ascertain cough persistence. Children who continue to cough for 28 days post enrolment are referred to a paediatric respiratory physician for review. Primary analysis will be the proportion of children with persistent cough at day 28(±3). Multivariate analyses will be performed to evaluate variables independently associated with chronic cough at day 28(±3). Discussion: Our protocol will be the first to comprehensively describe the natural history, epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children. The results will contribute to studies leading to the development of evidence-based clinical guidelines to improve the early detection and management of chronic cough in children during and after acute respiratory illness. [ABSTRACT FROM AUTHOR]

Abstract: While the discovery of HRV-Cs is recent, there are no indications that they are new viruses, or that they are emerging in real-time. Genetically, HRV-Cs are most closely related to the members of HRV-A and HRV-B but even a small genetic difference can impart encompass significant changes to their clinical impact, complicated by a diverse human background of prior virus exposure and underlying host immune and disease variability. It is well known that HRVs are a major trigger of asthma exacerbations and HRV-Cs are now under investigation for their potential involvement in asthma inception. The newly described HRV-Cs account for a large proportion of HRV-related illness, including common colds and wheezing exacerbations. HRV-Cs are genetically diverse and appear to circulate with seasonal variation, exchanging dominance with HRV-A. Whether HRV-Cs are consistently more pathogenic or “asthmagenic” is unproven. Antigenic diversity complicates passive and active prophylactic interventions (i.e. antibodies or vaccines), so further identification and characterisation of individual types (and their neutralising antigens) is likely to inform future preventive strategies. In the meantime, new antivirals should benefit groups at risk of the most severe disease. [Copyright &y& Elsevier]

Abstract: In tropical countries of Asia, like India, approximately 0.5 million children of <5years of age die annually due to acute respiratory illness (ARI). Of common respiratory pathogens, influenza viruses (A & B) are associated with annual worldwide epidemics; while the information on influenza C virus is inadequate. During January 2011 through December 2012, 2737 nasal and/or throat swabs were collected from patients reporting at outpatient department of hospitals in eastern India with ARI. Nucleotide sequencing was carried out using gene specific primers followed by pair-wise sequence alignments, multiple alignments, construction of phylogenetic tree and analysis of deduced amino acid sequences. Study reveals that, out of 2737 samples, 1616 (59.04%) were positive for one or more respiratory viruses; of which 23.72% were positive for influenza A and B viruses. From influenza A & B negative samples, influenza C virus was screened and detected with a frequency of 0.18%. Phylogenetic analysis showed that the HE, matrix, NS, PB1 and PB2 gene of the studied strain (C/Eastern-India/1202/2011) possessed a close relatedness to C/Yamagata/26/81 like strains. The P3 gene shows proximity with C/Mississipi/80 like strains whereas NP gene revealed similarity with C/Miyagi/1/93 like strains. The outcome of the whole genome analysis of the strain C/Eastern-India/1202/2011 provided useful information regarding genetic diversity of influenza C strains in India. [Copyright &y& Elsevier]

Inefficient cookstoves contribute to deforestation and global climate change, require substantial time (usually of women and girls) collecting wood or money for fuel and lead to just under two million deaths a year. We examined the effect of solar ovens on fuel use, time spent collecting wood, carbon monoxide exposure, and respiratory illness symptoms. A phased randomised controlled trial was run among women interested in purchasing a solar oven in rural Senegal. Of the envisioned 1000 households, 465 treatments and 325 controls took part in the baseline survey. Households randomly allocated to the control group received their stoves 6 months after treatments. Eighty per cent of our respondents typically cook for more people than the capacity of the solar oven and thus even cooks using the solar oven continue using their traditional stove. In the sixth month of owning the stove, treatments used their solar oven 19 per cent of days measured and did not have statistically significantly lower fuel consumption, time spent collecting fuel or time spent next to the cook fire. However, treatments cooking for 7–12 persons did lower their wood consumption for cooking by 14 per cent (P < .01). There is no evidence solar ovens reduced exposure to carbon monoxide or self-reported respiratory symptoms such as coughs and sore throats. This evaluation was a policy success because its results halted the proposed nationwide rollout of the solar oven, thus avoiding mass distribution of a stove which cannot reduce indoor air pollution or generate a sizeable decrease in fuel use. The results from this randomised controlled trial show that the HotPot is a poor product choice for the population as a one-pot stove cannot replace the three-stone fire for the lunch meal due to complex cooking patterns with multiple stoves, cooks and burners. A key result from our programme is stove designers – both solar and other improved biomass cookstoves – should reassess the product design to produce stoves that are affordable, durable, locally appropriate, consistent with current cooking practices (i.e., containing two burners) and large enough to accommodate multi-generational and/or polygamous households with limited incomes and no electricity. [ABSTRACT FROM PUBLISHER]

Background: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries. Active surveillance is essential to identify the causative agents and to improve clinical management, especially in the context of possible circulation of pandemic viruses. Findings: A prospective study was conducted in the Central African Republic (CAR) between January and December 2010 among infants and children aged 0-15 years attending sentinel sites for influenza-like illness or acute respiratory illness. Nasopharyngeal swabs were collected, and one-step real-time and multiplex reverse transcription-polymerase chain reaction were used to detect respiratory viruses. Respiratory viruses were detected in 49 of the 329 (14.9%) nasopharyngeal samples: 29 (8.8%) contained influenza viruses (5 (1.5%) had pandemic influenza A/H1N1 virus and 24 (7.3%) had influenza B viruses), 11 (3.3%) contained parainfluenza viruses types 1 and 3 and 9 (2.7%) contained human respiratory syncytial virus. Most cases were detected during the rainy season in the CAR. Analysis of the amplicon sequences confirmed the identity of each detected virus. Conclusions: The influenza surveillance system in the CAR has provided valuable data on the seasonality of influenza and the circulation of other respiratory viruses. Our network could therefore play a valuable role in the prevention and control of influenza epidemics in the CAR. [ABSTRACT FROM AUTHOR]

In 2005, human coronavirus HKU1 (HCoV-HKU1) was isolated and identified from a 71-year-old man with pneumonia in Hong Kong. To identify and classify genotypes of HCoV-HKU1 in Korea, a sensitive, specific, and quantitative real-time polymerase chain reaction (PCR) assay was developed and analyzed the sequences of HCoV-HKU1 isolated in Korea. A total of 1,985 respiratory specimens taken from patients with acute respiratory illness were tested for HCoV-HKU1 from January 2007 to May 2008. The major clinical symptoms associated with HCoV-HKU1 infection were examined statistically and sequence variations of the RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid genes were also analyzed. Fifty cases (2.5%) HCoV-HKU1 were identified by real-time PCR and viral loads ranged from 6.7 × 104 to 1.6 × 109 copies/ml. The clinical symptoms of HCoV-HKU1 infection included rhinorrhea (72%), cough (64%), nasal congestion (56%), fever (32%), sputum (30%), sore throat (18%), chills (16%), postnasal discharge (14%), and tonsillar hypertrophy (10%). There was a seasonal distribution of HCoV-HKU1 infection, peaking in winter and spring. Both genotypes A and B were detected but no recombination between them was found. This is the first report on the identification and genotyping of HCoV-HKU1 as a causative agent of acute respiratory illness in Korea. The data suggest that at least two genotypes, A and B, of HCoV-HKU1 with scattered silent mutations were circulating in Korea from 2007 to 2008. J. Med. Virol. 85:309-314, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The respiratory system is often affected by complications of immunodeficiency, typically manifesting clinically as acute respiratory illness. Ongoing literature reviews regarding the appropriateness of imaging in these patients are critical, as advanced medical therapies such as stem cell transplantation, chemotherapy, and immunosuppressive therapies for autoimmune disease continue to keep high the population of immunosuppressed patients in our health care system today. This ACR Appropriateness Criteria® topic describes clinical scenarios of acute respiratory illness in immunocompromised patients with cough, dyspnea, chest pain, and fever; in those with negative, equivocal, or nonspecific findings on chest radiography; in those with diffuse or confluent opacities on chest radiography; and in those in whom noninfectious disease is suspected. The use of chest radiography, chest CT, transthoracic needle biopsy, and nuclear medicine imaging are all discussed in the contexts of these clinical scenarios. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: WU and KI polyomaviruses (PyV) were discovered in 2007 in respiratory tract samples in adults and children. Other polyomaviruses (BKPyV and JCPyV) have been associated with illness in immunocompromised patients, and some studies suggest a higher prevalence of WUPyV and KIPyV in this population. Objective: To determine whether a higher prevalence or viral load for WUPyV and KIPyV exists in immunocompromised children compared with immunocompetent children. Study design: We measured the prevalence and viral load of WU and KI PyV by quantitative real-time PCR of viral DNA in respiratory tract specimens from pediatric hematology/oncology patients and immunocompetent controls with acute respiratory illnesses. Results: The prevalence of WUPyV in the immunocompromised population was 5/161 (3%) versus 14/295 (5%) in the control population (P =0.5), and 9/161 (5.6%) versus 7/295 (2.3%) respectively for KIPyV (P =0.13). The mean viral load (in copies per cell or mL of sample) for KIPyV, was higher in the immunocompromised group compared to the control group (P =0.019), but was not statistically different for WUPyV. A higher prevalence was seen in the hematopoietic stem cell transplant recipients compared with other immunocompromised patients (6/26 versus 3/43, P =0.054). Viral persistence was demonstrated only in 1/25 (4%) of sequential samples for KIPyV, and no persistence was seen for WUPyV. Conclusions: A higher prevalence of WUPyV or KIPyV in the immunocompromised population compared with the immunocompetent group was not demonstrated. Higher viral loads for KIPyV in the immunocompromised group may suggest an increased pathogenic potential in this population. [Copyright &y& Elsevier]

Abstract: Acute respiratory illnesses (ARI), comprising influenza-like illness (ILI) and other wintertime respiratory illnesses (ORI), impose substantial health and economic burdens on the United States. Little is known about the impact of ILI among household members (HHM), particularly children, on employees’ productivity. To quantify the impact of employee and HHM-ILI and ARI on employee productivity, a prospective, observational cohort study was conducted among employees from three large US companies. Employees who had at least one child living at home (N =2013) completed a monthly survey during the 2007–2008 influenza season, reporting the number of days missed from work and hours of presenteeism due to: (1) personal ILI, (2) HHM-ILI, and (3) personal and HHM-ARI. Employee ILI ranged from 4.8% (April) to 13.5% (February). Employees reporting ILI reported more absences than employees not reporting ILI (72% vs 30%, respectively; P <0.001). Overall, 61.2% of employees surveyed had at least one child with an ILI; these employees missed more days of work due to HHM illness than employees without an ARI-ill child (0.9 days vs 0.3 days, respectively; P <0.001). Employees with ILI were less productive, on average, for 4.8h each day that they worked while sick, 2.5h of which was attributable to ILI. HHM illnesses accounted for 17.7% (1389/7868 days) of employee absenteeism, over half of which was due to HHM-ARI. ILI causes a significant amount of employee absence. Household members, particularly children, comprise a sizable proportion of general illness and injury-related employee absences. [Copyright &y& Elsevier]

The Haemophilus influenzae type b (Hib) conjugate vaccine has been administered for almost 20 years in developed countries with remarkable success. More recently, the vaccine has been introduced in resource-poor settings, mainly those in Africa. African countries have documented large declines in Hib-invasive disease following universal vaccine introduction based on evaluation of routine surveillance data. As of 2007, only Mongolia in Asia had introduced the vaccine. Consequently, studies are limited to clinical trials in Bangladesh and Indonesia, and these also demonstrate substantial vaccine impact. Beyond invasive disease, three pivotal trials in Africa and Asia have demonstrated vaccine impact against clinical pneumonia end points. In all settings evaluated, Hib vaccine was shown to be cost effective, although the vaccine is not yet cost saving based on pentavalent vaccine prices in excess of US$3 per dose. Future issues include monitoring for serotype replacement and the effects of the HIV epidemic, evaluating the usefulness of a booster dose or new vaccine schedules and working to lower vaccine prices. [ABSTRACT FROM AUTHOR]

OBJECTIVE. We aimed to investigate differences in upper and lower respiratory tract symptoms in relation to respiratory viral infections detected with polymerase chain reaction assays in young children with cystic fibrosis and healthy control subjects. METHODS. In a 6-month winter period, 20 young children with cystic fibrosis and 18 age-matched, healthy, control subjects were contacted twice per week for detection of symptoms of an acute respiratory illness. If any symptom was present, then a home visit was made for physical examination and collection of nasopharyngeal swabs for viral analysis. In addition, parents were instructed to collect nasopharyngeal swabs every 2 weeks. RESULTS. Children with cystic fibrosis and healthy control subjects had similar frequencies of acute respiratory illnesses (3.8 ± 1.0 and 4.2 ± 1.7 episodes, respectively). Although there were no significant differences in upper respiratory tract symptoms, the children with cystic fibrosis had longer periods of lower respiratory tract symptoms (22.4 ± 22.2 vs 12.8 ± 13.8 days) and a higher mean severity score per episode (2.35 ± 0.64 vs 1.92 ± 0.46). In addition, similar increases in upper respiratory tract symptom scores were associated with significantly greater increases in lower respiratory tract symptom scores in children with cystic fibrosis. No differences in the seasonal occurrences and distributions of respiratory viruses were observed, with picornaviruses and coronaviruses being the most prevalent. CONCLUSIONS.Although there were no differences in the seasonal occurrences and distributions of polymerase chain reaction-detected respiratory viruses, acute respiratory illnesses were frequently associated with increased lower respiratory tract morbidity in young children with cystic fibrosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age. Objectives: Identify candidate pathogens in pediatric patients with unexplained respiratory disease. Study design: Forty-four nasopharyngeal washes collected during the 2004–2005 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis. Results: Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR. Conclusions: Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease. [Copyright &y& Elsevier]

Influenza disease impacts every year up to 10% of the world’s population, i.e. up to 500 millions of people. The international surveillance network organised by WHO allows the detection of important antigenic variation of the virus in humans but also animals (especially birds and pigs). Epidemiological data are summarised twice a year in two meetings (one in February, the other in September) allowing WHO to propose new recommendations for vaccines formulations for each northern and southern hemisphere influenza season annual vaccination. According to such recommendation, vaccine manufacturers proceed each year with two different vaccine production campaigns in order to match the vaccine composition with global epidemiological surveillance data and so, develop each time an updated vaccine formulation. To date within 6 months production periods, almost 250 million of doses are brought annually on market in more than 100 countries. In such a tight schedule, the annual production requires careful coordination of a highly complex process involving both public health laboratories and vaccine companies, in order to provide on time safe and effective vaccines. Major steps of this vaccine production process including the milestones and the bottlenecks need to be detailed in order to well understand difficulties and hurdles towards increase of global capacity and introduction of new vaccines. [Copyright &y& Elsevier]

During 2018-2019, a severe human adenovirus (HAdV) infection outbreak occurred in southern China. Here, we screened 18 respiratory pathogens in 1704 children (≤ 14 years old) hospitalized with acute respiratory illness in Guangzhou, China, in 2019. In total, 151 patients had positive HAdV test results; 34.4% (52/151) of them exhibited severe illness. HAdV infection occurred throughout the year, with a peak in summer. The median patient age was 3.0 (interquartile range: 1.1-5.0) years. Patients with severe HAdV infection exhibited increases in 12 clinical indexes (P ​≤ ​0.019) and decreases in four indexes (P ​≤ ​0.007), compared with patients exhibiting non-severe infection. No significant differences were found in age or sex distribution according to HAdV infection severity (P ​> ​0.05); however, the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity (P ​< ​0.05). The main epidemic types were HAdV-3 (47.0%, 71/151) and HAdV-7 (46.4%, 70/151). However, the severe illness rate was significantly higher in patients with HAdV-7 (51.4%) than in patients with HAdV-3 (19.7%) and other types of HAdV (20%) (P ​< ​0.001). Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates. A representative HAdV-7 isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhou01 (accession no. DQ099432) (P ​> ​0.05); the HAdV-7 isolate exhibited stronger virulence and infectivity, compared with HAdV-3 (P ​< ​0.001). Overall, comorbid disease, HAdV co-infection, and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection; these data can facilitate treatment, control, and prevention of HAdV infection., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Objectives: In mainland China, the disease burden of influenza is not yet fully understood. Based on population-based data, we aimed to estimate incidence rates of medically attended influenza and influenza virus infections in Ningbo City., Methods: We used data for outpatient acute respiratory illness (OARI) from a platform covering all health and medical institutes in Yingzhou District, Ningbo City. We applied generalized additive regression models to estimate influenza-associated excess incidence rate of OARI by age. We recruited local residents aged ≥60 years in the autumn of 2019 and conducted follow-up nearly 9 months later. Every survey, the sera were collected for testing hemagglutination inhibition antibody., Results: From 2017-2018 to 2019-2020, the annual average of influenza-associated incidence rate of OARI in all ages was 10.9%. The influenza-associated incidence rate of OARI was the highest in 2017-2018 (16.9%) and the lowest in 2019-2020 (4.8%). Regularly, influenza-associated incidence rates of OARI were the highest in children aged 5-14 years (range: 44.1-77.6%) and 0-4 years (range: 8.3-46.6%). The annual average of excess OARI incidence rate in all ages was the highest for influenza B/Yamagata (3.9%). The overall incidence rate of influenza infections indicated by serology in elderly people was 21% during the winter season of 2019-2020., Conclusions: We identified substantial outpatient influenza burden in all ages in Ningbo. Our cohort study limited in elderly people found that this age group had a high risk of seasonal influenza infections. Our study informs the importance of increasing influenza vaccine coverage in high-risk population including elderly people., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Aim: To test the internal validity of the test-negative design (TND) by investigating associations between maternal influenza vaccination, and new virus detection episodes (VDEs), acute respiratory illness, and healthcare visits in their children., Methods: Eighty-five children from a birth cohort provided daily symptoms, weekly nasal swabs, and healthcare use data until age 2-years. Effect estimates are summarised as incidence rate ratios (IRR)., Results: There was no association between maternal vaccination and VDEs in children (IRR = 1.1; 95 %CI = 0.9-1.2). Influenza-vaccinated mothers were more likely than unvaccinated mothers to both report, and seek healthcare for, acute lower respiratory illness in their children, IRR = 2.4; 95 %CI = 1.2-4.8 and IRR = 2.2; 95 %CI = 1.1-4.3, respectively., Conclusion: A key assumption of the TND, that healthcare seeking behaviour for conditions of the same severity is not associated with vaccine receipt, did not hold. Further studies of the performance of the TND in different populations are required to confirm its validity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Rapid diagnostic tests (RDTs) for influenza used by individuals at home could potentially expand access to testing and reduce the impact of influenza on health systems. Improving access to testing could lead to earlier diagnosis following symptom onset, allowing more rapid interventions for those who test positive, including behavioral changes to minimize spread. However, the accuracy of RDTs for influenza has not been determined in self-testing populations., Objective: This study aims to assess the accuracy of an influenza RDT conducted at home by lay users with acute respiratory illness compared with that of a self-collected sample by the same individual mailed to a laboratory for reference testing., Methods: We conducted a comparative accuracy study of an at-home influenza RDT (Ellume) in a convenience sample of individuals experiencing acute respiratory illness symptoms. Participants were enrolled in February and March 2020 from the Greater Seattle region in Washington, United States. Participants were mailed the influenza RDT and reference sample collection materials, which they completed and returned for quantitative reverse-transcription polymerase chain reaction influenza testing in a central laboratory. We explored the impact of age, influenza type, duration, and severity of symptoms on RDT accuracy and on cycle threshold for influenza virus and ribonuclease P, a marker of human DNA., Results: A total of 605 participants completed all study steps and were included in our analysis, of whom 87 (14.4%) tested positive for influenza by quantitative reverse-transcription polymerase chain reaction (70/87, 80% for influenza A and 17/87, 20% for influenza B). The overall sensitivity and specificity of the RDT compared with the reference test were 61% (95% CI 50%-71%) and 95% (95% CI 93%-97%), respectively. Among individuals with symptom onset ≤72 hours, sensitivity was 63% (95% CI 48%-76%) and specificity was 94% (95% CI 91%-97%), whereas, for those with duration >72 hours, sensitivity and specificity were 58% (95% CI 41%-74%) and 96% (95% CI 93%-98%), respectively. Viral load on reference swabs was negatively correlated with symptom onset, and quantities of the endogenous marker gene ribonuclease P did not differ among reference standard positive and negative groups, age groups, or influenza subtypes. The RDT did not have higher sensitivity or specificity among those who reported more severe illnesses., Conclusions: The sensitivity and specificity of the self-test were comparable with those of influenza RDTs used in clinical settings. False-negative self-test results were more common when the test was used after 72 hours of symptom onset but were not related to inadequate swab collection or severity of illness. Therefore, the deployment of home tests may provide a valuable tool to support the management of influenza and other respiratory infections., (©Rachel E Geyer, Jack Henry Kotnik, Victoria Lyon, Elisabeth Brandstetter, Monica Zigman Suchsland, Peter D Han, Chelsey Graham, Misja Ilcisin, Ashley E Kim, Helen Y Chu, Deborah A Nickerson, Lea M Starita, Trevor Bedford, Barry Lutz, Matthew J Thompson. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 22.02.2022.)

Background: Whether acute respiratory illnesses (ARIs), often associated with virus detection, are associated with lower risk for subsequent ARI remains unclear. We assessed the association between symptomatic ARI and subsequent ARI in young children., Methods: In a prospective cohort of Peruvian children <3 years, we examined the impact of index ARI on subsequent ARI risk. Index ARI were matched with ≤3 asymptomatic observations and followed over 28 days. We compared risk of subsequent ARI between groups using conditional logistic regression adjusting for several covariates, accounting for repeat observations from individual children., Results: Among 983 index ARI, 339 (34%) had an ARI event during follow-up, compared with 876/2826 (31%) matched asymptomatic observations. We found no significant association of index ARI and subsequent ARI risk during follow-up overall (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI], .98-1.23) or when limited to index ARI with respiratory viruses detected (aOR, 1.03; 95% CI, .86-1.24). Similarly, when the outcome was limited to ARI in which viruses were detected, no significant association was seen (aOR, 1.05; 95% CI, .87-1.27)., Conclusions: ARIs were not associated with short-term protection against subsequent ARI in these children. Additional longitudinal studies are needed to understand drivers of recurrent ARI in young children., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We established cohorts to assess associations between viral influenza and cognitive development to inform the value proposition of vaccination., Methods: From 2014 through 2017, we called women seeking care at four prenatal clinics in Panama and El Salvador to identify acute respiratory illnesses (ARIs). Within 2 weeks of childbirth, mothers were asked to enroll their neonates in the cognitive development study. Staff obtained nasopharyngeal swabs from children with febrile ARIs for real-time reverse transcription polymerase chain reaction (rtPCR) detection of viral RNA. Toddlers were administered Bayley developmental tests at ages 12 and 18-24 months. We used multilevel linear regression to explore associations between Bayley scores, ARIs, fever, and laboratory-confirmed influenza, controlling for maternal respiratory or Zika illnesses, infant influenza vaccination, birth during influenza epidemics, and the number of children in households., Results: We enrolled 1567 neonates of which 68% (n = 1062) underwent developmental testing once and 40% (n = 623) twice. Children with previous ARIs scored an average of 3 points lower on their cognitive scores than children without ARIs (p = 0.001). Children with previous fevers scored an average of 2.1 points lower on their cognitive scores than afebrile children (p = 0.02). In the second year, children with previous laboratory-confirmed influenza scored 4 points lower on their cognitive scores than children without influenza (p = 0.04, after controlling for first Bayley cognitive scores)., Conclusions: ARIs and fever during infancy were associated with lower Bayley scores at 12 months, and laboratory-confirmed influenza was associated with lower cognitive scores at 24 months suggesting the potential value of vaccination to prevent non-respiratory complications of influenza., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

The sudden outbreak of the novel coronavirus infection (COVID-19, SARS-CoV-2 virus) is posing a significant threat by affecting millions of people across the globe showing mild to severe symptoms of pneumonia and acute respiratory distress. The absence of precise information on primary transmission, diagnosis, prognosis, and therapeutics for patients with COVID-19 makes prevention and control tough. In the current scenario, only supportive treatment is available, which in turn possess a biggest challenge for scientists to develop specific drugs and vaccines for COVID-19. Further, India, with the second largest populated country and fluctuating climatic conditions quarterly, has high vulnerability towards COVID-19 infection. Thus, this highlights the importance of a better understanding of the COVID-19 infection, pathology, diagnosis and its treatment. The present review article has been intended to discuss the COVID-19 biology, mechanism of infection in humans with primary effects on pregnancy, the nervous system, diabetes, and cardiovascular disease. The article will also discuss the drug repurposing strategy as an alternative line of treatment and clinical practices recommended by the World Health Organization and other government agencies and represent the COVID-19 scenario with the Indian context., Competing Interests: Conflict of InterestSKM, AB, PS, and RM declare no conflict of interest., (© The National Academy of Sciences, India 2022.)

Objective: To better understand public beliefs and use of antibiotics for acute respiratory illnesses.Design: Cross-sectional telephone survey.Participants: Three hundred eighty-six adult members (aged 18 years or older) of a group-model HMO in the Denver metropolitan area.Measurements and Main Results: Two hundred seventy-three (70%) of the respondents reported that antibiotics were beneficial for bacterial respiratory illnesses, 211 (55%) reported that antibiotics were beneficial for viral respiratory illnesses, and 82 (21%) reported that antibiotics were beneficial for bacterial but not for viral illness. Multivariate regression analysis identified consulting an advice nurse (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.7, 5.3), ever being told by a provider that antibiotics were not needed for a respiratory illness episode (OR 2.0; 95% CI 1.2, 3.6), having a chronic medical condition (OR 2.0; 95% CI 1.0, 3.9), and believing antibiotics to be helpful for viral (OR 2.5; 95% CI 1.3, 4.7) or bacterial (OR 2.6; 95% CI 1.2, 6.7) respiratory illnesses to be independently associated with antibiotic use for respiratory illnesses during the previous year. There was a trend toward lower previous antibiotic use among those believing antibiotics to be helpful for bacterial illness but not for viral illness.Conclusions: A lack of understanding about antibiotic effectiveness exists in the community. Increased previous antibiotic use among those believing antibiotics to be effective for viral illnesses suggests that improvements are needed in communications to patients and the public about antibiotic appropriateness. [ABSTRACT FROM AUTHOR]

Objectives: To describe the clinical features of adults diagnosed with acute bronchitis, and to identify clinical variables associated with antibiotic treatment of acute bronchitis.Design: Prospective, cohort study.Setting: Primary care office practices at a group-model HMO in the Denver metropolitan area.Patients/participants: Patients were adults seeking care for acute respiratory illnesses. Participating clinicians included internists, family medicine physicians, nurse practitioners, physician assistants, and registered nurses.Measurements and Main Results: Clinicians voluntarily completed encounter forms for patients presenting with acute respiratory illnesses between February and May, 1996. Acute bronchitis was the primary diagnosis in 16% of acute respiratory illness visits (n = 1,525). The most frequent symptoms of acute bronchitis were cough (92%), phlegm production (63%), "runny nose" (50%), and throat pain (50%). The most frequent physical examination findings were pharyngeal erythema (45%), cervical lymphadenopathy (19%), wheezes (18%), and rhonchi (17%). Antibiotics were prescribed to 85% of patients diagnosed with acute bronchitis. Purulent nasal discharge by patient report, and sinus tenderness on physical examination were moderately associated with antibiotic treatment (p = .06 and .08, respectively). Antibiotic prescription rates did not vary by patient age or gender, duration of illness, days of work lost due to illness, or clinician type.Conclusions: Acute bronchitis is frequently treated with antibiotics in ambulatory practice. The clinical factors we identified to be associated with antibiotic use for acute bronchitis appear to play a minor role in explaining the excessive use of antibiotics for this condition. These findings suggest that clinicians use the diagnosis of acute bronchitis as an indication for antibiotic treatment, despite clinical trials and expert recommendations to the contrary. [ABSTRACT FROM AUTHOR]

We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed substantial reductions in pneumococcal and Staphylococcus aureus carriage and rapid expansion in the abundance of certain resistance genes., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)