COVID-19 orphans—Global patterns associated with the hidden pandemic

Whilst the COVID-19 pandemic has caused significant mortality across the globe, many children have been orphaned due to the loss of their parents. Using the framework of an ecological analysis, we used estimates of total maternal/paternal orphans using an online COVID-19 orphanhood calculator to estimate the total orphans per COVID-19 death for 139 countries. Descriptive statistics were used to determine global patterns behind this risk of children being orphaned. Linear regression models were fitted to determine factors associated with this risk, and the association with vaccination coverage was calculated. We found that there is tremendous global variation in the risk that COVID-19 deaths will lead to orphaned children, and that this risk is higher in countries below median GDP per capita (1·56 orphans per deaths) compared to countries above (0·09 orphans per death). Poverty prevalence (B = 2·32, p<0·01), GDP per capita (B = -0·23, p<0·05), and a greater proportion of people with NCDs being reproductive aged (B = 1·46, p<0·0001) were associated with this risk. There was a negative correlation between 2nd dose vaccination coverage and orphans per death (p<0·05). The risk of children being orphaned per COVID-19 death, alongside fertility rate, is due to there being a greater share of COVID-19 deaths among younger persons. This is more likely in poorer countries and those where the age distribution for non-communicable diseases that elevate COVID-19 mortality risk are more uniform. Due to vaccine coverage inequity, more children will suffer the loss of their parents in poorer countries.

Team effectiveness: epidemiologists' perception of collective performance during emergency response.

BACKGROUND: To describe epidemiologists' experience of team dynamics and leadership during emergency response, and explore the utility of the Team Emergency Assessment Measure (TEAM) tool during future public health emergency responses. The TEAM tool included categories for leadership, teamwork, and task management. METHODS: We conducted a cross-sectional survey between October 2019 and February 2020 with the global applied field epidemiology workforce. To validate the TEAM tool for our context, we used exploratory and confirmatory factor analysis. RESULTS: We analysed 166 completed surveys. Respondents included national and international emergency responders with representation of all WHO regions. We were unable to validate the TEAM tool for use with epidemiology teams involved in emergency response, however descriptive analysis provided insight into epidemiology emergency response team performance. We found female responders were less satisfied with response leadership than male counterparts, and national responders were more satisfied across all survey categories compared to international responders. CONCLUSION: Functional teams are a core attribute of effective public health emergency response. Our findings have shown a need for a greater focus on team performance. We recommend development of a fit-for-purpose performance management tool for teams responding to public health emergencies. The importance of building and supporting the development of the national workforce is another important finding of this study.

COVID-19 orphans-Global patterns associated with the hidden pandemic.

Whilst the COVID-19 pandemic has caused significant mortality across the globe, many children have been orphaned due to the loss of their parents. Using the framework of an ecological analysis, we used estimates of total maternal/paternal orphans using an online COVID-19 orphanhood calculator to estimate the total orphans per COVID-19 death for 139 countries. Descriptive statistics were used to determine global patterns behind this risk of children being orphaned. Linear regression models were fitted to determine factors associated with this risk, and the association with vaccination coverage was calculated. We found that there is tremendous global variation in the risk that COVID-19 deaths will lead to orphaned children, and that this risk is higher in countries below median GDP per capita (1·56 orphans per deaths) compared to countries above (0·09 orphans per death). Poverty prevalence (B = 2·32, p<0·01), GDP per capita (B = -0·23, p<0·05), and a greater proportion of people with NCDs being reproductive aged (B = 1·46, p<0·0001) were associated with this risk. There was a negative correlation between 2nd dose vaccination coverage and orphans per death (p<0·05). The risk of children being orphaned per COVID-19 death, alongside fertility rate, is due to there being a greater share of COVID-19 deaths among younger persons. This is more likely in poorer countries and those where the age distribution for non-communicable diseases that elevate COVID-19 mortality risk are more uniform. Due to vaccine coverage inequity, more children will suffer the loss of their parents in poorer countries.

Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies.

There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.

One Health Approach: A Data-Driven Priority for Mitigating Outbreaks of Emerging and Re-Emerging Zoonotic Infectious Diseases.

This paper discusses the contributions that One Health principles can make in improving global response to zoonotic infectious disease. We highlight some key benefits of taking a One Health approach to a range of complex infectious disease problems that have defied a more traditional sectoral approach, as well as public health policy and practice, where gaps in surveillance systems need to be addressed. The historical examples demonstrate the scope of One Health, partly from an Australian perspective, but also with an international flavour, and illustrate innovative approaches and outcomes with the types of collaborative partnerships that are required.

Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients.

AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.