BACKGROUND: Regional monitoring of the proportion of the population who have been infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. We aimed to estimate in near real time the proportion of adults who have been infected by SARS-CoV-2. METHODS: In this modelling study, we developed a method to reconstruct the proportion of adults who have been infected by SARS-CoV-2 and the proportion of infections being detected, using the joint analysis of age-stratified seroprevalence, hospitalisation, and case data, with deconvolution methods. We developed our method on a dataset consisting of seroprevalence estimates from 9782 participants (aged ≥20 years) in the two worst affected regions of France in May, 2020, and applied our approach to the 13 French metropolitan regions over the period March, 2020, to January, 2021. We validated our method externally using data from a national seroprevalence study done between May and June, 2020. FINDINGS: We estimate that 5·7% (95% CI 5·1-6·4) of adults in metropolitan France had been infected with SARS-CoV-2 by May 11, 2020. This proportion remained stable until August, 2020, and increased to 14·9% (13·2-16·9) by Jan 15, 2021. With 26·5% (23·4-29·8) of adult residents having been infected in Île-de-France (Paris region) compared with 5·1% (4·5-5·8) in Brittany by January, 2021, regional variations remained large (coefficient of variation [CV] 0·50) although less so than in May, 2020 (CV 0·74). The proportion infected was twice as high (20·4%, 15·6-26·3) in 20-49-year-olds than in individuals aged 50 years or older (9·7%, 6·9-14·1). 40·2% (34·3-46·3) of infections in adults were detected in June to August, 2020, compared with 49·3% (42·9-55·9) in November, 2020, to January, 2021. Our regional estimates of seroprevalence were strongly correlated with the external validation dataset (coefficient of correlation 0·89). INTERPRETATION: Our simple approach to estimate the proportion of adults that have been infected with SARS-CoV-2 can help to characterise the burden of SARS-CoV-2 infection, epidemic dynamics, and the performance of surveillance in different regions. FUNDING: EU RECOVER, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale (Inserm).

An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1β, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.

PURPOSE: To assess the associations between adherence to 24-hour movement behaviors guidelines and child general health and functional status measured by health-related quality of life. METHODS: The Longitudinal Study of Australian Children (2004-2016) a nationally representative sample with data available for children aged 2-15 years was used. Physical activity time, recreational screen time, and sleep time were calculated from time use diaries and classified as 'meeting guidelines' or 'not' based on the age-specific 24-h movement guidelines. Child general health and functional status were measured using the multidimensional Pediatric Quality of Life Inventory (PedsQL). Associations between meeting guidelines and PedsQL were assessed using linear mixed effects models. RESULTS: 8919 children were included. Each additional guideline met was associated with a 0.52 (95% confidence interval [CI] 0.39-0.65) increase in PedsQL total score. Compared with meeting no guidelines, the effect of meeting physical activity guidelines alone (β = 0.93, 95% CI 0.42-1.44) was larger compared to meeting screen (β = 0.66, 95% CI 0.06-1.27) or sleep time (β = 0.47, 95% CI 0.04-0.89) guidelines alone. The highest increment was observed in meeting both screen time and physical activity guidelines (β = 1.89, 95% CI 1.36-2.43). Associations were stronger in children from lower-income families (β for meeting all versus none = 2.88, 95% CI 1.77-3.99) and children aged 14-15 years (β = 4.44, 95% CI 2.49-6.40). CONCLUSIONS: The integration of screen time and physical activity guidelines is associated with the highest PedsQL improvement. The association between guidelines adherence and PedsQL appears stronger for adolescents and those from low-income families.

Unprotected sexual transmission is the cause of approximately 70%-80% of human immunodeficiency virus (HIV) infections worldwide. Prevalence of HIV infection in 2011 was more than ten fold higher (3.8%) among men who have sex with men (MSM) than in the general population (0.33%) in Nepal. This study aimed to explore sexual behaviors, and social and demographic characteristics of MSM in Kathmandu Valley, Nepal. A quantitative cross sectional study was conducted among 113 MSM. MSM is a hidden population in Nepalese society, therefore, it was difficult to construct a sample frame for this research so, respondent driven sampling was used which gives unbiased estimates of population parameters and has the potential to reach MSM, who are not easily accessible. A structured interview was used to obtain the information. The majority of respondents were above 20 years old (mean = 27.9 years, SD = 7.4 years). Most respondents were receptive, 43.4% identified themselves as Meti. Forty six percent of respondents were married. The majority had sex with males which was predominantly anal. MSM had an average number of 74 sex partners (last three months). Nearly 95% had used a condom, and 92% had used lubricant during their last sex act. Thirty eight percent perceived themselves as at risk of HIV. The majority knew of a place for confidential HIV testing in Kathmandu. This study highlights the importance of partner tracing during HIV counseling and testing, the importance of drop-in centers to increase access to condoms, and supports the need to increase comprehensive health services and peer led participatory behavioral change communication activities to this population in the national HIV response.

INTRODUCTION: The COVID-19 pandemic demanded a rapid response within Radiation Oncology services to minimise the risk of infection to patients and workforce. This study aimed to assess whether the operational changes put in place to reduce infection risks were effective in engaging and supporting staff. METHODS: Our service's response saw staff and patients split into morning or afternoon shifts without overlap. Changes included extended clinic hours, modified treatment regimens, expanded online/electronic communication and remote working. Staff were invited to respond to an electronic questionnaire in September 2020, just after the peak of the second COVID-19 wave in Victoria. Responses captured demographic data, parental status, profession, happiness levels, fear of COVID-19 and e-communication efficacy. RESULTS: A 57% response rate was achieved. 69% of respondents were female; 40% were aged 45+ and 35% had school-aged children. Staff aged 45+ showed a significantly greater fear of COVID-19 than younger staff. 36% of respondents reported feeling nervous or anxious watching news reports about COVID-19. 92% of staff were happy with their work arrangements; staff with children were happier than staff without children with their shifts. Online chat/channels were reported as the preferred e-communication method between colleagues. CONCLUSION: Staff provided predominantly positive feedback to the changes made in response to the pandemic, reporting high levels of happiness and willingness to continue with the changes implemented during COVID-19. The strategies adopted worked well and the overall high levels of staff satisfaction will allow our service to quickly pivot should further surges, or another pandemic, arise.

COVID-19 had a variable impact on urgent interventions among hospitalized patients in Ontario Canada.

BACKGROUND: Prior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection. METHODS: Children with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture. RESULTS: The median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L). CONCLUSIONS: Children with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.

BACKGROUND: The comparative yield of respiratory virus detection from nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain. Furthermore, the significance of virus detection and its relationship to lower airway neutrophilic inflammation is poorly studied. OBJECTIVES: To evaluate the sensitivity, specificity and predictive values of NPA for detecting respiratory viruses in BAL; and to determine the relationship between viruses and lower airway neutrophilia in children with non-acute respiratory illness. STUDY DESIGN: 150 paired NPA and BAL samples were obtained from 75 children aged <18 years undergoing flexible bronchoscopy for investigation of chronic respiratory symptoms. Viral studies were performed using polymerase chain reaction (PCR). Cellularity studies were performed on BALs. Diagnostic parameters of NPA compared to BAL and associations between viruses and lower airway %neutrophils were evaluated. RESULTS: NPA had a higher yield than BAL for detection of any respiratory virus (52 versus 38, respectively). NPA had a high sensitivity (92%) and low specificity (57%) for detecting HRV in BAL with poor kappa agreement value of 0.398 (95% CI 0.218-0.578, p<0.001). NPA had a fair sensitivity (69%) and good specificity (90.3%) for detecting HAdV on BAL, kappa agreement was 0.561 (95% CI 0.321-0.801, p<0.001). HAdV positivity on NPA, compared to negativity, was independently associated with heightened airway neutrophilia [mean difference (95% CI): 18 (1,35); p=0.042]. CONCLUSIONS: NPA has a higher yield for respiratory virus detection than BAL, however its diagnostic accuracy is dependent on viral species. Adenovirus positivity is associated with significantly heightened lower airway neutrophilia in children with chronic respiratory symptoms.

BACKGROUND: The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). METHODS: Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. RESULTS: Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). CONCLUSIONS: HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.