Understanding the risk of transmission of respiratory viral infections in childcare centres: protocol for the DISeases TrANsmission in ChildcarE (DISTANCE) multicentre cohort study.

INTRODUCTION: Childcare centre is considered a high-risk setting for transmission of respiratory viruses. Further evidence is needed to understand the risk of transmission in childcare centres. To this end, we established the DISeases TrANsmission in ChildcarE (DISTANCE) study to understand the interaction among contact patterns, detection of respiratory viruses from environment samples and transmission of viral infections in childcare centres. METHODS AND ANALYSIS: The DISTANCE study is a prospective cohort study in multiple childcare centres of Jiangsu Province, China. Study subjects will be childcare attendees and teaching staff of different grades. A range of information will be collected from the study subjects and participating childcare centres, including attendance, contact behaviours (collected by onsite observers), respiratory viral infection (weekly respiratory throat swabs tested by multiplex PCR), presence of respiratory viruses on touch surfaces of childcare centres and weekly follow-up survey on respiratory symptoms and healthcare seeking among subjects tested positive for any respiratory viruses. Detection patterns of respiratory viruses from study subjects and environment samples, contact patterns, and transmission risk will be analysed by developing statistical and mathematical models as appropriate. The study has been initiated in September 2022 in 1 childcare centre in Wuxi City, with a total of 104 children and 12 teaching staff included in the cohort; data collection and follow-up is ongoing. One more childcare centre in Nanjing City (anticipated to include 100 children and 10 teaching staff) will start recruitment in 2023. ETHICS AND DISSEMINATION: The study has received ethics approval from Nanjing Medical University Ethics Committee (No. 2022-936) and ethics approval from Wuxi Center for Disease Control and Prevention Ethics Committee (No. 2022-011). We plan to disseminate the study findings mainly through publications in peer-reviewed journals and presentations in academic conferences. Aggregated research data will be shared freely to researchers.

SARS-CoV-2 infection of intestinal epithelia cells sensed by RIG-I and DHX-15 evokes innate immune response and immune cross-talk.

SARS-CoV-2 causes a spectrum of clinical symptoms from respiratory damage to gastrointestinal disorders. Intestinal infection of SARS-CoV-2 triggers immune response. However, the cellular mechanism that how SARS-CoV-2 initiates and induces intestinal immunity is not understood. Here, we exploited SARS-CoV-2-GFP/ΔN trVLP pseudo-virus system and demonstrated that RIG-I and DHX15 are required for sensing SARS-CoV-2 and inducing cellular immune response through MAVS signaling in intestinal epithelial cells (IECs) upon SARS-CoV-2 infection. NLRP6 also engages in the regulation of SARS-CoV-2 immunity by producing IL-18. Furthermore, primary cellular immune response provoked by SARS-CoV-2 in IECs further cascades activation of MAIT cells and produces cytotoxic cytokines including IFN-γ, granzyme B via an IL-18 dependent mechanism. These findings taken together unveil molecular basis of immune recognition in IECs in response to SARS-CoV-2, and provide insights that intestinal immune cross-talk with other immune cells triggers amplified immunity and probably contributes to immunopathogenesis of COVID-19.

Evaluation of COVID-19 vaccines in primary prevention against infections and reduction in severity of illness following the outbreak of SARS-CoV-2 omicron variant in Shanghai.

Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessen the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Data sources: Data from 153,544 COVID-19 patients admitted to the Shanghai "Four-Leaf Clover" Fangcang makeshift shelter hospital were collected using a structured electronic questionnaire, which was then merged with electronic medical records of the hospital. For healthy controls, data on vaccination status and other information were obtained from 228 community-based residents, using the same structured electronic questionnaire. Methods: To investigate whether inactivated vaccines were effective in protecting against SARS-CoV-2 virus, we estimated the odds ratio (OR) of the vaccination by comparing cases and matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied multivariate stepwise logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in the COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Results: Of the 153,544 COVID-19 patients included in the analysis, the mean age was 41.59 years and 90,830 were males (59.2%). Of the study cohort, 118,124 patients had been vaccinated (76.9%) and 143,225 were asymptomatic patients (93.3%). Of the 10,319 symptomatic patients, 10,031 (97.2%), 281 (2.7%), and 7 (0.1%) experienced mild, moderate, and severe infections, respectively. Hypertension (8.7%) and diabetes (3.0%) accounted for the majority of comorbidities. There is no evidence that the vaccination helped protect from infections (OR = 0.82, p = 0.613). Vaccination, however, offered a small but significant protection against symptomatic infections (RR = 0.92, p < 0.001) and halved the risk of moderate/severe infections (OR = 0.48, 95% CI: 0.37-0.61). Older age (≥60 years) and malignant tumors were significantly associated with moderate/severe infections. Conclusion: Inactivated COVID-19 vaccines helped provide small but significant protection against symptomatic infections and halved the risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking the SARS-CoV-2 Omicron Variant community spread.

Changes following the Onset of the COVID-19 Pandemic in the Burden of Hospitalization for Respiratory Syncytial Virus Acute Lower Respiratory Infection in Children under Two Years: A Retrospective Study from Croatia.

To understand the changes in RSV hospitalization burden in children younger than two years following the onset of the COVID-19 pandemic, we reviewed hospital records of children with acute lower respiratory infection (ALRI) between January 2018 and June 2022 in Split-Dalmatia County, Croatia. We compared RSV activity, age-specific annualized hospitalization rate, and disease severity between pre-COVID-19 and COVID-19 periods. A total of 942 ALRI hospital admissions were included. RSV activity remained low for the typical RSV epidemic during 2020-2021 winter. An out-of-season RSV resurgence was observed in late spring and summer of 2021. Before the COVID-19 pandemic, the annualized hospitalization rate for RSV-associated ALRI was 13.84/1000 (95% CI: 12.11-15.76) and highest among infants under six months. After the resurgence of RSV in the second half of 2021, the annualized hospitalization rate for RSV-associated ALRI in children younger than two years returned to the pre-pandemic levels with similar age distribution but a statistically higher proportion of severe cases. RSV immunization programs targeting protection of infants under six months of age are expected to remain impactful, although the optimal timing of administration would depend on RSV seasonality that has not yet been established in the study setting since the onset of the COVID-19 pandemic.

Effect of inactivated COVID-19 vaccination on pregnancy outcomes following frozen-thawed embryo transfer: A retrospective cohort study.

OBJECTIVE: To investigate the effect of inactivated coronavirus disease 2019 (COVID-19) vaccination on frozen-thawed embryo transfer (FET) outcomes. METHODS: This retrospective cohort study enrolled 1,210 patients undergoing FET cycles in a single university-affiliated hospital between July 1, 2021, and May 1, 2022. Of them, 387 women with two full doses of inactivated SARS-CoV-2 vaccines (CoronaVac or BBIBP-CorV) after oocyte retrieval were assigned to the vaccinated group, while 823 were unvaccinated as controls. Propensity score matching and multiple regression analysis were applied to control for baseline and cycle characteristics (19 covariates in total). RESULTS: There were 265 patients in each group after matching. The rates of clinical pregnancy (58.5% vs. 60.8%; P = 0.595) and live birth (44.4% vs. 48.8%; P = 0.693) were similar between vaccinated and unvaccinated patients, with adjusted odds ratios of 0.89 (95% confidence interval [CI] 0.61-1.29) and 1.31 (95% CI 0.37-4.56), respectively. Consistently, no significant differences were found in serum human chorionic gonadotropin levels as well as biochemical pregnancy, biochemical pregnancy loss, and embryo implantation rates. Based on the time interval from vaccination to FET, vaccinated patients were further subdivided into two categories of ≤2 months and >2 months, and the outcomes remained comparable. CONCLUSION: Our study showed that inactivated COVID-19 vaccination in women did not have measurable detrimental impact on implantation performance and live birth outcome during FET treatment cycles. This finding denies the impairment of endometrial receptivity and trophoblast function by vaccine-induced antibodies at the clinical level.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Corneal Complications after COVID-19 Vaccination: A Systemic Review.

Multiple vaccines are now being used across the world, and several studies have described cases of corneal graft rejection following the administration of the COVID-19 vaccine. The purpose of this article is to review the corneal adverse event that occurred following COVID-19 vaccine administration. The literature search was conducted in March 2022 using MEDLINE, PubMed, and the Cochrane Database of Systematic Reviews. A total of 27 articles, including 37 cases, have documented corneal adverse events that occurred following COVID-19 vaccination. The mean age was 60 ± 14.9 years (range, 27-83 years). The most common events were acute corneal graft rejection (n = 21, 56.8%), followed by herpes zoster ophthalmicus (n = 11, 29.7%) and herpes simplex keratitis (n = 2, 5.4%). The mean time from vaccination to the event was 10 ± 8.5 days (range, 1-42 days) after the first or second dose of vaccine. All patients with corneal graft rejection, immune-mediated keratolysis, and peripheral ulcerative keratitis (PUK) (n = 24, 64.9%) were managed topically with or without oral corticosteroids. Patients with herpes zoster ophthalmicus and herpes simplex keratitis were managed with oral antiviral agents. Two patients received penetrating keratoplasty due to keratolysis after invalid topical treatment. Disease resolution was noted in 29 patients (78.3%), whereas 3 (8.1%) had persistent corneal edema after graft rejection, 1 (2.7%) had corneal infiltration after HZO, and 4 (10.8%) were not mentioned in the articles. Corneal adverse events could occur after COVID-19 vaccination. After timely treatment with steroids or antiviral agents, most of the events were mild and had a good visual outcome. Administrating or increasing steroids before vaccination may be useful for the prevention of corneal graft rejection. However, the prophylactic use of antiviral treatments in patients with a herpes viral infection history is not recommend.

The relationship between trait mindfulness and subjective wellbeing of kindergarten teachers: The sequential mediating role of emotional intelligence and self-efficacy

This study explored the relationship between emotional intelligence and self-efficacy in trait mindfulness and subjective wellbeing. In this study, 323 Chinese kindergarten teachers were measured using the Five Facet Mindfulness Questionnaire, Emotional Intelligence Scale, General Self-efficacy Scale, and Subjective Wellbeing Scale. The study found that subjective wellbeing can be predicted directly from trait mindfulness (β = 0.257, p < 0.001). Emotional intelligence could mediate the relationship between trait mindfulness and subjective wellbeing (β = 0.165, p = 0.006). Self-efficacy could mediate the relationship between trait mindfulness and subjective wellbeing (β = 0.078, p = 0.032). In addition, emotional intelligence and self-efficacy played a sequential mediating role between trait mindfulness and subjective wellbeing (β = 0.072, p = 0.005). This study revealed the relationship between kindergarten teachers’ trait mindfulness and subjective wellbeing through structural equation modeling and understood its role path, enriching the research on the Chinese preschool teachers in the field, and providing a literature reference for the international community to understand the Chinese kindergarten teachers. At the same time, the study also has some limitations, such as the use of a cross-sectional design method, a relatively single method, and the impact of COVID-19. However, we believe that this study will further enrich the research literature on the relationship between trait mindfulness and subjective wellbeing of Chinese kindergarten teachers.

Short-term local predictions of COVID-19 in the United Kingdom using dynamic supervised machine learning algorithms.

Background: Short-term prediction of COVID-19 epidemics is crucial to decision making. We aimed to develop supervised machine-learning algorithms on multiple digital metrics including symptom search trends, population mobility, and vaccination coverage to predict local-level COVID-19 growth rates in the UK. Methods: Using dynamic supervised machine-learning algorithms based on log-linear regression, we explored optimal models for 1-week, 2-week, and 3-week ahead prediction of COVID-19 growth rate at lower tier local authority level over time. Model performance was assessed by calculating mean squared error (MSE) of prospective prediction, and naïve model and fixed-predictors model were used as reference models. We assessed real-time model performance for eight five-weeks-apart checkpoints between 1st March and 14th November 2021. We developed an online application (COVIDPredLTLA) that visualised the real-time predictions for the present week, and the next one and two weeks. Results: Here we show that the median MSEs of the optimal models for 1-week, 2-week, and 3-week ahead prediction are 0.12 (IQR: 0.08-0.22), 0.29 (0.19-0.38), and 0.37 (0.25-0.47), respectively. Compared with naïve models, the optimal models maintain increased accuracy (reducing MSE by a range of 21-35%), including May-June 2021 when the delta variant spread across the UK. Compared with the fixed-predictors model, the advantage of dynamic models is observed after several iterations of update. Conclusions: With flexible data-driven predictors selection process, our dynamic modelling framework shows promises in predicting short-term changes in COVID-19 cases. The online application (COVIDPredLTLA) could assist decision-making for control measures and planning of healthcare capacity in future epidemic growths.

The role of respiratory co-infection with influenza or respiratory syncytial virus in the clinical severity of COVID-19 patients: A systematic review and meta-analysis.

Background: With the easing of COVID-19 non-pharmaceutical interventions, the resurgence of both influenza and respiratory syncytial virus (RSV) was observed in several countries globally after remaining low in activity for over a year. However, whether co-infection with influenza or RSV influences disease severity in COVID-19 patients has not yet been determined clearly. We aimed to understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients. Methods: We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (ie, influenza/RSV with SARS-CoV-2) and mono-infection group (ie, SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation, and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses where applicable. Results: Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection were found to be associated with a higher risk of ICU admission (five studies, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.64-2.68) and mechanical ventilation (five studies, OR = 2.31, 95% CI = 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (four studies, OR = 1.04, 95% CI = 0.37-2.95; 11 studies, OR = 1.41, 95% CI = 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (three studies, OR = 5.27, 95% CI = 0.58-47.87). Conclusions: Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients. Registration: PROSEPRO CRD42021283045.

Age-Specific Estimates of Respiratory Syncytial Virus-Associated Hospitalizations in 6 European Countries: A Time Series Analysis.

BACKGROUND: Knowledge on age-specific hospitalizations associated with RSV infection is limited due to limited testing, especially in older children and adults in whom RSV infections are not expected to be severe. Burden estimates based on RSV coding of hospital admissions are known to underestimate the burden of RSV. We aimed to provide robust and reliable age-specific burden estimates of RSV-associated hospital admissions based on data on respiratory infections from national health registers and laboratory-confirmed cases of RSV. METHODS: We conducted multiseason regression analysis of weekly hospitalizations with respiratory infection and weekly laboratory-confirmed cases of RSV and influenza as covariates, based on national health registers and laboratory databases across 6 European countries. The burden of RSV-associated hospitalizations was estimated by age group, clinical diagnosis, and presence of underlying medical conditions. RESULTS: Across the 6 European countries, hospitalizations of children with respiratory infections were clearly associated with RSV, with associated proportions ranging from 28% to 60% in children younger than 3 months and we found substantial proportions of admissions to hospital with respiratory infections associated with RSV in children younger than 3 years. Associated proportions were highest among hospitalizations with ICD-10 codes of "bronchitis and bronchiolitis." In all 6 countries, annual incidence of RSV-associated hospitalizations was >40 per 1000 persons in the age group 0-2 months. In age group 1-2 years the incidence rate ranged from 1.3 to 10.5 hospitalizations per 1000. Adults older than 85 years had hospitalizations with respiratory infection associated to RSV in all 6 countries although incidence rates were low. CONCLUSIONS: Our findings highlight the substantial proportion of RSV infections among hospital admissions across different ages and may help public health professionals and policy makers when planning prevention and control strategies. In addition, our findings provide valuable insights for health care professionals attending to both children and adults presenting with symptoms of viral respiratory infections.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Research priorities to reduce the impact of COVID-19 in low- and middle-income countries

Background The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs. Methods The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability;2) potential for burden reduction;3) potential for a paradigm shift;4) potential for translation and implementation;and 5) impact on equity. Results Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients’ needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts. Interpretation Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.

The role of respiratory co-infection with influenza or respiratory syncytial virus in the clinical severity of COVID-19 patients: a systematic review and meta-analysis (preprint)

Aim: To understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients. Methods: We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (i.e., influenza/RSV with SARS-CoV-2) and mono-infection group (i.e., SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses, where applicable. Results: Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection was found to be associated with a higher risk of ICU admission (5 studies, OR: 2.09, 95% CI: 1.64-2.68) and mechanical ventilation (5 studies, OR: 2.31, 95% CI: 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (4 studies, OR: 1.04, 95% CI: 0.37-2.95;11 studies, OR: 1.41, 95% CI: 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (3 studies, OR: 5.27, 95% CI: 0.58-47.87). Conclusions: Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients.

Understanding the Potential Drivers for Respiratory Syncytial Virus Rebound During the Coronavirus Disease 2019 Pandemic.

Nonpharmaceutical interventions (NPIs) were widely introduced to combat the coronavirus disease 2019 (COVID-19) pandemic. These interventions also likely led to substantially reduced activity of respiratory syncytial virus (RSV). From late 2020, some countries observed out-of-season RSV epidemics. Here, we analyzed the role of NPIs, population mobility, climate, and severe acute respiratory syndrome coronavirus 2 circulation in RSV rebound through a time-to-event analysis across 18 countries. Full (re)opening of schools was associated with an increased risk for RSV rebound (hazard ratio [HR], 23.29 [95% confidence interval {CI}, 1.09-495.84]); every 5°C increase in temperature was associated with a decreased risk (HR, 0.63 [95% CI, .40-.99]). There was an increasing trend in the risk for RSV rebound over time, highlighting the role of increased population susceptibility. No other factors were found to be statistically significant. Further analysis suggests that increasing population susceptibility and full (re)opening of schools could both override the countereffect of high temperatures, which explains the out-of-season RSV epidemics during the COVID-19 pandemic.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Automatic cough detection from realistic audio recordings using C-BiLSTM with boundary regression.

Automatic cough detection in the patients' realistic audio recordings is of great significance to diagnose and monitor respiratory diseases, such as COVID-19. Many detection methods have been developed so far, but they are still unable to meet the practical requirements. In this paper, we present a deep convolutional bidirectional long short-term memory (C-BiLSTM) model with boundary regression for cough detection, where cough and non-cough parts need to be classified and located. We added convolutional layers before the LSTM to enhance the cough features and preserve the temporal information of the audio data. Considering the importance of the cough event integrity for subsequent analysis, the novel model includes an embedded boundary regression on the last feature map for both higher detection accuracy and more accurate boundaries. We delicately designed, collected and labelled a realistic audio dataset containing recordings of patients with respiratory diseases, named the Corp Dataset. 168 h of recordings with 9969 coughs from 42 different patients are included. The dataset is published online on the MARI Lab website (https://mari.tongji.edu.cn/info/1012/1030.htm). The results show that the system achieves a sensitivity of 84.13%, a specificity of 99.82% and an intersection-over-union (IoU) of 0.89, which is significantly superior to other related models. With the proposed method, all the criteria on cough detection significantly increased. The open source Corp Dataset provides useful material and a benchmark for researchers investigating cough detection. We propose the state-of-the-art system with boundary regression, laying the foundation for identifying cough sounds in real-world audio data.

Global hospital admissions and in-hospital mortality associated with all-cause and virus-specific acute lower respiratory infections in children and adolescents aged 5-19 years between 1995 and 2019: a systematic review and modelling study.

INTRODUCTION: The burden of acute lower respiratory infections (ALRI), and common viral ALRI aetiologies among 5-19 years are less well understood. We conducted a systematic review to estimate global burden of all-cause and virus-specific ALRI in 5-19 years. METHODS: We searched eight databases and Google for studies published between 1995 and 2019 and reporting data on burden of all-cause ALRI or ALRI associated with influenza virus, respiratory syncytial virus, human metapneumovirus and human parainfluenza virus. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We developed an analytical framework to report burden by age, country and region when there were sufficient data (all-cause and influenza-associated ALRI hospital admissions). We estimated all-cause ALRI in-hospital deaths and hospital admissions for ALRI associated with respiratory syncytial virus, human metapneumovirus and human parainfluenza virus by region. RESULTS: Globally, an estimated 5.5 million (UR 4.0-7.8) all-cause ALRI hospital admissions occurred annually between 1995 and 2019 in 5-19 year olds, causing 87 900 (UR 40 300-180 600) in-hospital deaths annually. Influenza virus and respiratory syncytial virus were associated with 1 078 600 (UR 4 56 500-2 650 200) and 231 800 (UR 142 700-3 73 200) ALRI hospital admissions in 5-19 years. Human metapneumovirus and human parainfluenza virus were associated with 105 500 (UR 57 200-181 700) and 124 800 (UR 67 300-228 500) ALRI hospital admissions in 5-14 years. About 55% of all-cause ALRI hospital admissions and 63% of influenza-associated ALRI hospital admissions occurred in those 5-9 years globally. All-cause and influenza-associated ALRI hospital admission rates were highest in upper-middle income countries, Asia-Pacific region and the Latin America and Caribbean region. CONCLUSION: Incidence and mortality data for all-cause and virus-specific ALRI in 5-19 year olds are scarce. The lack of data in low-income countries and Eastern Europe and Central Asia, South Asia, and West and Central Africa warrants efforts to improve the development and access to healthcare services, diagnostic capacity, and data reporting.

Recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding in a patient with COVID-19: a case report.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) global pandemic caused by the SARS-CoV-2 virus remains a major threat to public health. At present, it is recommended that patients with known or suspected COVID-19 undergo quarantine or medical observation for 14 days. However, recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding have been documented in convalescent COVID-19 patients, complicating efforts to control viral spread and ensure patient recovery. CASE PRESENTATION: We report the case of a patient who experienced two recurrent episodes of SARS-CoV-2 RNA and IgM positivity and viral shedding over 60 days during hospitalization. CONCLUSIONS: This case report demonstrates that relapses of SARS-CoV-2 RNA and IgM positivity may occur even after COVID-19 symptoms have resolved, possibly as a consequence of prolonged viral shedding rather than re-infection.