Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood

This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies

Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population

Comparison of nasopharyngeal nylon flocked swabs with universal transport medium and rayon- bud swabs with a sponge reservoir of viral transport medium in the diagnosis of paediatric influenza

This study compared a kit containing a nasopharyngeal nylon flocked swab and a tube with a liquid universal transport medium (UTM) with a kit containing a plastic-shafted rayon-budded swab with a sponge reservoir of viral transport medium for the molecular detection of influenza viruses in children. Respiratory samples were collected from 314 children aged ,5 years with influenza-like illness (186 males; mean age 2.32±2.27 years) using both swabs in a randomized sequence for each patient. The flocked swabs permitted the detection of 28 influenza A (8.9 %) and 45 influenza B (14.3 %) cases, and the rayon-bud swabs 26 influenza A (8.3 %) and 43 influenza B (13.7 %) cases, with detection rates of 23.2 and 22.0 %, respectively, and similar cycle threshold values. Paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. These findings show that the flocked swabs with UTM and the rayon-bud swabs with a sponge transport medium are similarly efficient in preserving influenza virus nucleic acid, but that the kit containing a flocked swab with a UTM allows easier and more rapid collection and processing of specimens. INTRODUCTION Respiratory infections are the most common diseases of infants and children Antigen detection tests and PCR-based methods are both currently used to detect viruses in respiratory secretions There are various kits containing a nasopharyngeal swab and a tube with transport medium on the market, but only a few studies, mainly of adults, have compared their efficiency in collecting respiratory cells and preserving influenza virus nucleic acid Sample collection. Two samples were collected from each patient and transported by means of two kits: one containing a flexible nasopharyngeal nylon flocked swab and a mini-tube with 1 ml liquid universal transport medium (UTM; Copan Italia), and the other a rayon-budded swab with a tube containing a sponge pre-impregnated with transport medium (Virocult; Medical Wire &amp; Equipment). Using the swabs in a randomized sequence, two nasopharyngeal samples were collected from each child (one from each nostril) by trained paediatricians (L. C., L. G. and S. B.). The distance between the patient&apos;s nares and ear lobe was measured to estimate the length of insertion, after which the swabs were gently inserted towards the pharynx until resistance was felt and then rotated three times to obtain epithelial cells. They were then withdrawn and put into the tube containing the specific transport medium. All of the specimens were kept cool and delivered to the laboratory within 3 h of collection. Sample processing. In the laboratory, each swab was processed in triplicate by three researchers (C. G. M., C. D. and A. V.) as indicated by the manufacturers: 190 ml of the liquid transport medium for the flocked swabs was used directly, whereas the rayon-budded swabs were placed in a tube containing 1 ml liquid lysis buffer (the same amount as that contained in the mini-UTM), the tube was vortexed and incubated for 10 min at room temperature, and 190 ml of the solution was used for extraction. PCR. Viral RNA was extracted from all of the samples by means of a NucliSENS EasyMAG automated extraction system (bioMeriéux), using phocine distemper virus (PDV) as an extraction/PCR inhibition control as described previously (Bosis et al., 2005; Staff satisfaction. Trained paediatricians and members of the laboratory staff were asked to record their satisfaction with the simplicity and rapidity using the swabs after the enrolment of each patient or the completion of the analysis of each pair of swabs by completing a 5-point scale (from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;). Statistical analysis. The data relating to the paired specimens collected from 314 children (186 males, 59.2 %), with a mean age of 2.32±2.27 years, were compared using SAS version 9.1 software (SAS Institute). Continuous variables were analysed using Wilcoxon&apos;s signed rank test or rank sum test as appropriate, and the categorical variables by means of contingency tables and a x 2 or Fisher&apos;s test. RESULTS AND DISCUSSION Satisfaction was based on a 5-point scale from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;. .20 for influenza B virus. However, the paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and the rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. Our study showed that the flocked swabs with UTM and the rayon-budded swabs with transport medium preimpregnated sponge were similarly efficient in preserving influenza virus nucleic acid, but that the former were considered better in terms of the simplicity and rapidity of collection and laboratory testing. Systematic evaluation of the aetiology of paediatric respiratory infections is increasingly being considered an important means of preventing their spread and rationalizing therapy Our main finding was that the paediatricians preferred the flocked swabs because they were more flexible and made it easier and quicker to collect the samples. In addition, the laboratory staff found that the kit containing a flocked swab and liquid transport medium was advantageous insofar as it allowed RNA extraction and PCR to be performed directly on the liquid without the need to add further buffer, whereas the kit containing a transport medium pre-impregnated sponge required an additional step that made the procedure more complicated, timeconsuming and at risk of contamination. One limitation of this study is represented by the fact that the interpretation of the results on simplicity and rapidity of collection and laboratory testing may be devalued by repeated scoring and clustering by the same staff members. This means that further studies that involve several swab collectors and laboratory researchers are required to confirm our results. Moreover, our aim was to compare the efficiency of the two kits in detecting influenza virus nucleic acid, but further studies are required to evaluate the sensitivity of the two transport systems with serial dilutions of positive samples of influenza A and B viruses. Finally, a complete comparison of the sensitivity and specificity of the two kits should also include detection of other respiratory viruses that are commonly found in respiratory samples (e.g. respiratory syncytial virus, adenovirus, rhinovirus), and future research should address this aim. In conclusion, both the flocked swabs with UTM and the rayon-bud swabs with a sponge reservoir of viral transport medium allow adequate collection, transport and preservation of nasal secretions for influenza detection. However, the kit containing a flocked swab with a liquid transport medium facilitated rapid specimen collection and processing. These factors should be considered together with local costs when choosing a product to use in clinical practice. ACKNOWLEDGEMENT

Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009

<p>Abstract</p> <p>Background</p> <p>There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness.</p> <p>Methods</p> <p>Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households.</p> <p>Results</p> <p>Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05).</p> <p>Conclusions</p> <p>Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.</p

Safety Profile and Outcomes of Early COVID-19 Treatments in Immunocompromised Patients: A Single-Centre Cohort Study

Background: Early treatment with remdesivir (RMD) or monoclonal antibodies (mAbs) could be a valuable tool in patients at risk of severe COVID-19 with unsatisfactory responses to vaccination. We aim to assess the safety and clinical outcomes of these treatments among immunocompromised subjects. Methods: We retrospectively reviewed all nonhospitalized patients who received an early treatment with RMD or mAbs for COVID-19, from 25 November 2021 to 25 January 2022, in a large tertiary hospital. Outcomes included frequency of adverse drug reaction (ADR), duration of symptoms and molecular swab positivity, emergency department access, hospital or intensive care unit admission, and mortality in the 14 days following treatment administration. Results: Early treatments were administered to 143 patients, 106/143 (74.1%) immunocompromised, including 41 solid organ and 6 hematopoietic stem cell transplant recipients. Overall, 23/143 (16.1%) subjects reported ADRs. Median time from treatment start to SARS-CoV-2 nasopharyngeal swab negativity and symptom resolution was 10 (IQR 6&ndash;16) and 2.5 days (IQR 1.0&ndash;6.0), respectively, without differences between immunocompromised and nonimmunocompromised patients. In the 14 days after treatment administration, 5/143 patients (3.5%) were hospitalized and one died as a result of causes related to COVID-19, all of them were immunocompromised. Conclusions: RMD and mAbs have minimal ADRs and favourable outcomes in immunocompromised patients

Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use