Sustainable strategies for Ebola virus disease outbreak preparedness in Africa: a case study on lessons learnt in countries neighbouring the Democratic Republic of the Congo.

BACKGROUND: From May 2018 to September 2022, the Democratic Republic of Congo (DRC) experienced seven Ebola virus disease (EVD) outbreaks within its borders. During the 10th EVD outbreak (2018-2020), the largest experienced in the DRC and the second largest and most prolonged EVD outbreak recorded globally, a WHO risk assessment identified nine countries bordering the DRC as moderate to high risk from cross border importation. These countries implemented varying levels of Ebola virus disease preparedness interventions. This case study highlights the gains and shortfalls with the Ebola virus disease preparedness interventions within the various contexts of these countries against the background of a renewed and growing commitment for global epidemic preparedness highlighted during recent World Health Assembly events. MAIN TEXT: Several positive impacts from preparedness support to countries bordering the affected provinces in the DRC were identified, including development of sustained capacities which were leveraged upon to respond to the subsequent coronavirus disease 2019 (COVID-19) pandemic. Shortfalls such as lost opportunities for operationalizing cross-border regional preparedness collaboration and better integration of multidisciplinary perspectives, vertical approaches to response pillars such as surveillance, over dependence on external support and duplication of efforts especially in areas of capacity building were also identified. A recurrent theme that emerged from this case study is the propensity towards implementing short-term interventions during active Ebola virus disease outbreaks for preparedness rather than sustainable investment into strengthening systems for improved health security in alignment with IHR obligations, the Sustainable Development Goals and advocating global policy for addressing the larger structural determinants underscoring these outbreaks. CONCLUSIONS: Despite several international frameworks established at the global level for emergency preparedness, a shortfall exists between global policy and practice in countries at high risk of cross border transmission from persistent Ebola virus disease outbreaks in the Democratic Republic of Congo. With renewed global health commitment for country emergency preparedness resulting from the COVID-19 pandemic and cumulating in a resolution for a pandemic preparedness treaty, the time to review and address these gaps and provide recommendations for more sustainable and integrative approaches to emergency preparedness towards achieving global health security is now.

Cortical and subcortical grey matter volume alterations in neuropsychiatric long-COVID syndrome episode

Introduction Neuropsychiatric symptoms are among the most common sequelae of long-COVID-19 and highly diminish the patient's quality of life. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it appears necessary to further investigate brain structural changes in relation to clinical long-COVID symptoms. Understanding the pathogenic processes in neuropsychiatric long-COVID will be vital to identify targeted therapy and to ease the months long-lasting symptoms. Methods The present cross-sectional study investigated 3T-MRI scans from long-COVID patients (n=30) with neuropsychiatric symptoms, and healthy controls matched for age and gender (n=20). Whole-brain comparison of grey matter volume (GMV) was conducted by voxel-based morphometry using the CAT12 software package. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and / or initial severity of symptoms of COVID19 and time since onset of COVID-19, we performed multiple linear regression analysis. Results Enlarged GMV in long-COVID patients was present in several clusters (p<0.05, FWE- corr-ected) spanning frontotemporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres when compared to controls. Time since onset of COVID-19 was a significant regressor in three of these clusters (anatomically located in right inferior frontal gyrus, lateral and posterior orbital gyrus, anterior parts of the insula, left superior, middle and inferior temporal gyrus and left postcentral and precentral gyrus). Conclusion Grey matter alterations in limbic and secondary olfactory areas are present in neuropsychiatric long-COVID patients. Some GMV alterations were inversely associated with time elapsed since acute COVID-19, suggesting higher GMV with shorter time since onset of COVID-19. Detection of associations between GMV and clinical symptoms might be difficult, because of heterogenous clinical presentation. Larger samples and longitudinal data in neuropsychiatric long-COVID patients are required to further clarify the mediating mechanisms between COVID-19 and GMV.

Hospital Costs of Extracorporeal Membrane Oxygenation in Adults: A Systematic Review.

BACKGROUND: Costs associated with extracorporeal membrane oxygenation (ECMO) are an important factor in establishing cost effectiveness. In this systematic review, we aimed to determine the total hospital costs of ECMO for adults. METHODS: The literature was retrieved from the PubMed/MEDLINE, EMBASE, and Web of Science databases from inception to 4 March 2020 using the search terms 'extracorporeal membrane oxygenation' combined with 'costs'; similar terms or phrases were then added to the search, i.e. 'Extracorporeal Life Support' or 'ECMO' or 'ECLS' combined with 'costs'. We included any type of study (e.g. randomized trial or observational cohort) evaluating hospital costs of ECMO in adults (age ≥18 years). RESULTS: A total of 1768 unique articles were retrieved during our search. We assessed 74 full-text articles for eligibility, of which 14 articles were selected for inclusion in this review; six papers were from the US, five were from Europe, and one each from Japan, Australia, and Taiwan. The sample sizes ranged from 16 to 18,684 patients. One paper exclusively used prospective cost data collection, while all other papers used retrospective data collection. Five papers reported charges instead of costs. There was large variation in hospital costs, ranging from US$22,305 to US$334,608 (2019 values), largely depending on the indication for ECMO support and location. The highest reported costs were for lung transplant recipients who were receiving ECMO support in the US, and the lowest reported costs were for extracorporeal cardiopulmonary resuscitation patients presenting with non-shockable rhythm in Japan. The additional costs of ECMO patients compared with non-ECMO patients varied between US$2518 and US$200,658. Personnel costs varied between 11 and 52% of the total amount. CONCLUSIONS: ECMO therapy is an advanced and expensive technology, although reported costs differ considerably depending on ECMO indication and whether charges or costs are measured. Combined with the ongoing gathering of outcome data, cost effectiveness per ECMO indication could be determined in the future.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19–Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis

IMPORTANCE: Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19–induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN, SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a “control” non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19–related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19–associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27;95% CI, 0.82–1.98;p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS.

Effects of the COVID-19 pandemic on suicide attempts in a rural region in Germany, a 5-year observational study.

BACKGROUND: The COVID-19 pandemic and public life restrictions may have a negative impact on people's mental health. Therefore, we analyzed whether this condition affected the occurrence of suicide attempts (SA) over 20 months during the pandemic period. METHODS: We included patient records according to DSM-5 criteria for suicidal behavior disorders (n = 825) between Jan 1, 2017, and Dec 31, 2021. We applied interrupted time-series Poisson regression models to investigate the effect of the pandemic on SA occurrence, time trends, and seasonal patterns in the whole group of patients as well as stratified by age and gender. RESULTS: There was no significant effect of the pandemic on the occurrence of SA in the overall group. However, we observed a significant impact of the pandemic on the seasonal pattern of SA, also the variance differed significantly (pre-pandemic mean ± variance: 13.33 ± 15.75, pandemic: mean ± variance: 13.86 ± 7.26), indicating less periodic variation in SA during the pandemic. Male patients and young adults mainly contributed to this overall effect. Subgroup analysis revealed a significant difference in SA trends during the pandemic in older adults (>55 years) compared with younger adults (18-35 years); SA numbers increased in older adults and decreased in younger adults as the pandemic progressed. LIMITATIONS: A few patients may have received initial care in an emergency department after SA without being referred to psychiatry. CONCLUSIONS: In general, the COVID-19 pandemic and related measures did not significantly affect the occurrence of SA but did significantly affect the dynamics. In addition, the pandemic appeared to affect suicidal behavior differently across age groups as it progressed. Particularly for the older adult group, negative long-term effects of the pandemic on suicidal behavior can be derived from the present results, indicating the need to strengthen suicide prevention for the elderly.

A shift from reactionary towards more proactive and sustainable approaches is required for effective Ebola virus disease preparedness in Africa: A case study of key lessons learned from the Democratic Republic of Congo (preprint)

Background From May 2018 to the end of June 2022, the Democratic Republic of Congo (DRC) experienced six Ebola virus disease outbreaks within its borders. During the 10th EVD outbreak, the largest experienced in the DRC and the second largest and most prolonged EVD outbreak recorded globally, a WHO risk assessment identified nine countries bordering the DRC as moderate to high risk from cross border importation. Burundi, Rwanda, South Sudan and Uganda were classified as priority one countries while Angola, Central African Republic, Congo, Tanzania and Zambia as priority two. These countries implemented varying levels of Ebola virus disease preparedness interventions. This case study highlights the gains and shortfalls with the Ebola virus disease preparedness interventions against the background of a renewed and growing commitment for global epidemic preparedness highlighted during recent World Health Assembly events.Main text Several positive impacts from preparedness support to countries bordering the affected provinces in the DRC were identified, including development of sustained capacities which were leveraged upon to respond to the subsequent COVID-19 pandemic. Shortfalls such as lost opportunities in vertical approaches to response pillars such as surveillance, over dependence on external support and duplication of efforts especially in the areas of capacity building were also identified. A recurrent theme that emerged from this case study is the propensity towards implementing short-term interventions during Ebola virus disease outbreak preparedness and response rather than sustainable investment into strengthening systems for improved health security in alignment with IHR obligations and the Sustainable Development Goals.Conclusions Despite several international frameworks established at the global level for emergency preparedness, a shortfall exists between global policy and practice in countries at high risk of cross border transmission from persistent Ebola virus disease outbreaks in the Democratic Republic of Congo. With renewed global health commitment for country emergency preparedness resulting from the COVID-19 pandemic and cumulating in a resolution for a pandemic preparedness treaty, the time to review and address these gaps and provide recommendations for more sustainable approaches to emergency preparedness towards achieving global health security is now.

Optimization of COVID-19 vaccination and the role of individuals with a high number of contacts: A model based approach.

We report strong evidence of the importance of contact hubs (or superspreaders) in mitigating the current COVID-19 pandemic. Contact hubs have a much larger number of contacts than the average in the population, and play a key role on the effectiveness of vaccination strategies. By using an age-structures compartmental SEIAHRV (Susceptible, Exposed, Infected symptomatic, Asymptomatic, Hospitalized, Recovered, Vaccinated) model, calibrated from available demographic and COVID-19 incidence, and considering separately those individuals with a much greater number of contacts than the average in the population, we show that carefully choosing who will compose the first group to be vaccinated can impact positively the total death toll and the demand for health services. This is even more relevant in countries with a lack of basic resources for proper vaccination and a significant reduction in social isolation. In order to demonstrate our approach we show the effect of hypothetical vaccination scenarios in two countries of very different scales and mitigation policies, Brazil and Portugal.

Radiological findings in low-dose CT for COVID-19 pneumonia in 182 patients: Correlation of signs and severity with patient outcome.

ABSTRACT: To characterize computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) pneumonia and their value in outcome prediction.Chest CTs of 182 patients with a confirmed diagnosis of COVID-19 infection by real-time reverse transcription polymerase chain reaction were evaluated for the presence of CT-abnormalities and their frequency. Regarding the patient outcome each patient was categorized in 5 progressive stages and the duration of hospitalization was determined. Regression analysis was performed to find which CT findings are predictive for patient outcome and to assess prognostic factors for the hospitalization duration.Multivariate statistical analysis confirmed a higher age (OR = 1.023, P  =  .025), a higher total visual severity score (OR = 1.038, P  =  .002) and the presence of crazy paving (OR = 2.160, P  =  .034) as predictive parameters for patient outcome. A higher total visual severity score (+0.134 days; P  =  .012) and the presence of pleural effusion (+13.985 days, P  =  0.005) were predictive parameters for a longer hospitalization duration. Moreover, a higher sensitivity of chest CT (false negatives 10.4%; true positives 78.6%) in comparison to real-time reverse transcription polymerase chain reaction was obtained.An increasing percentage of lung opacity as well as the presence of crazy paving and a higher age are associated with a worse patient outcome. The presence of a higher total visual severity score and pleural effusion are significant predictors for a longer hospitalization duration. These results are underscoring the value of chest CT as a diagnostic and prognostic tool in the pandemic outbreak of COVID-19, to facilitate fast detection and to preserve the limited (intensive) care capacity only for the most vulnerable patients.

Covid-19: HSS/ Horizon Scanning Living Document (v01 April 2020) Part 1;Covid-19: HSS/ Horizon Scanning Living Document (v01 April 2020) Part 2 (Appendix)

Objectives:In March 30th 2020, a request was raised by the Austrian Ministry of Health (BMASGK) and further Austrian policy stakeholder to set up a Horizon Scanning System (HSS) for medicines and vaccines. The establishment of a HSS/ Horizon Scanning System for Covid-19 interventions has the intention of a. informing health policy makers at an early stage which interventions (vaccinations and drugs) are currently undergoing clinical trials and b. monitoring them over the next few months in order to support evidence-based purchasing, if necessary. Methods:To respond to the request by BMASGK, 1. As a first step an inventory, based on international sources, is being built. 2. As a second step, selective searches by means of searches in study registries are carried out for information on clinical studies in humans and the state of research. 3. The information gathered in the first two steps forms the basis for "vignettes" (short descriptions) for those products that are already at an "advanced" stage. 4. Subsequently, the products are being monitored with regard to their status of clinical studies up to approval and are finally evaluated for their benefit and harm. All work steps are conducted in close international (European) cooperation.

CellHeap: A Workflow for Optimizing COVID-19 Single-Cell RNA-Seq Data Processing in the Santos Dumont Supercomputer

Currently, several hundreds of Terabytes of COVID-19 single-cell RNA-seq (scRNA-seq) data are available in public repositories. This data refers to multiple tissues, comorbidities, and conditions. We expect this trend to continue, and it is realistic to predict amounts of COVID-19 scRNA-seq data increasing to several Petabytes in the coming years. However, thoughtful analysis of this data requires large-scale computing infrastructures, and software systems optimized for such platforms to generate biological knowledge. This paper presents CellHeap, a portable and robust workflow for scRNA-seq customizable analyses, with quality control throughout the execution steps and deployable on supercomputers. Furthermore, we present the deployment of CellHeap in the Santos Dumont supercomputer for analyzing COVID-19 scRNA-seq datasets, and discuss a case study that processed dozens of Terabytes of COVID-19 scRNA-seq raw data. © 2021, Springer Nature Switzerland AG.

Covid-19: HSS/ Horizon Scanning Living Document (v01 April 2020) Part 1;Covid-19: HSS/ Horizon Scanning Living Document (v01 April 2020) Part 2 (Appendix)

Objectives:In March 30th 2020, a request was raised by the Austrian Ministry of Health (BMASGK) and further Austrian policy stakeholder to set up a Horizon Scanning System (HSS) for medicines and vaccines. The establishment of a HSS/ Horizon Scanning System for Covid-19 interventions has the intention of a. informing health policy makers at an early stage which interventions (vaccinations and drugs) are currently undergoing clinical trials and b. monitoring them over the next few months in order to support evidence-based purchasing, if necessary. Methods:To respond to the request by BMASGK, 1. As a first step an inventory, based on international sources, is being built. 2. As a second step, selective searches by means of searches in study registries are carried out for information on clinical studies in humans and the state of research. 3. The information gathered in the first two steps forms the basis for "vignettes" (short descriptions) for those products that are already at an "advanced" stage. 4. Subsequently, the products are being monitored with regard to their status of clinical studies up to approval and are finally evaluated for their benefit and harm. All work steps are conducted in close international (European) cooperation.

Roadside ditch macroplastic and other litter dataset in the Finger lakes region across land uses and COVID-19 pandemic.

Litter was collected from 12 roadside ditches in the Finger lakes Region of New York State over two sampling periods: pre-COVID-19 pandemic and during COVID-19 pandemic. Litter pieces were washed in DI water, oven dried, massed and plastic-type visually determined. Macroplastic data was analysed to assess the impact of land use, traffic, and COVID-19 variables on macroplastic accumulation on a piece, mass, and plastic-type basis. These data are all litter pieces collected, including both plastics categorized as 1 through 7 in the RIC resin classification codes as well as non-plastic litter. These data have wide-ranging reuse potential, as terrestrial microplastic accumulation is not well documented. These data could be compared with other litter accumulation across regions, specifically to assess total environmental macroplastic loading and enable contaminant mitigation strategies. These data also have direct application to modelling and transport of macroplastics into surface water bodies as a result of road ditch sampling locations. Macroplastic accumulation data across varying land uses, traffic, and COVID-19 conditions has been published [1].

Macroplastic accumulation in roadside ditches of New York State's Finger Lakes region (USA) across land uses and the COVID-19 pandemic.

Macroplastics are a ubiquitous and growing environmental contaminant with impacts in both marine and terrestrial systems. Marine sampling has dominated research in this field, despite the terrestrial origins of most plastic debris. Due to the high surface water connectivity facilitated by roadside ditches, these landscape features provide a unique sampling location linking terrestrial and surface water systems. We collected and analyzed macroplastic accumulation by number of pieces, mass, and polymer type in roadside ditches across four land uses, before and during the COVID-19 pandemic in the Finger Lakes Region of New York State. Commercial land use plastic accumulation rate was highest, while forested land use accumulation rates were lowest on a piece basis. Pre-COVID-19 piece accumulation rates were significantly higher than COVID-19 piece accumulation rates across all land uses. Mass accumulation rates followed similar patterns observed in piece accumulation, but the patterns were not always statistically significant. Plastic type 4 (i.e. thin plastic films), especially plastic bags and wrappers, was the most frequently collected type of macroplastic by piece across all land uses within the 1-7 Resin Identification Codes. By mass, the data were distributed less consistently across land uses. Cigarette filters, containing the polymer cellulose acetate, were the most frequently found roadside plastic, but are not within the 1-7 classification system. Our results suggest that policies in place limiting plastic bag usage could substantially reduce roadside plastics but other plastics, such as food wrappers and other single use plastic films, which comprised a large proportion of the plastic debris collected, should also be regulated to further decrease macroplastic pollution.

Saliva as a Reliable Sample for COVID-19 Diagnosis in Paediatric Patients (preprint)

Saliva has been described a less invasive and easy to handle sample, compared to nasopharyngeal swabs (NPS), in the diagnosis of COVID-19 in adults. Although the advantages of using saliva is still more evident in paediatric patients, little is now about its sensitivity in this group. The aim of this study was to compare the performance of saliva to that of NPS in the detection of SARS-CoV-2 in paediatric patients with mild symptoms. This study evaluated saliva samples from children with suspected COVID-19 who attended public healthcare services of Araraquara, Sao Paulo, Brazil. Children were asked to spit into a sterile container for collection of about 1ml of saliva after the NPS collection. SARS-COV-2 detection was performed by using the Altona RealStar(R) SARS-CoV-2 RT-PCR Kit 1.0. The sample consisted of 50 patients, in which 27 were girls (54%) and 23 were boys (46%). Ten were positive for SARS-CoV-2 in at least one sample collected. The mean age was 10.24 {+/-} 3.52 years old and saliva was collected after 4.76 {+/-} 1.31 days from the symptoms. Saliva and NPS have showed the same performance in the SARS-CoV-2 detection (k = 0.865, P < 0.001). In conclusion, saliva is a reliable alternative sample for COVID-19 diagnosis in paediatric population.

Could diet and exercise reduce risk of COVID-19 syndemic?

We present a hypothesis for increased sugar consumption and a lack of physical exercise as possible determinants of COVID-19 disease severity by impaired glucose metabolism, concurring into a syndemic. National data demonstrate that increased sugar consumption, a high daily caloric intake, and low levels of daily physical activity are independently associated with COVID-19 mortality. Further, genetic factors such as variations in the androgen receptor may compound the effects of an unhealthy lifestyle and increase the risk of severe COVID-19 symptoms in some patients. A diet high in sugar in combination with a low level of physical activity may increase blood glucose levels and impair glucose metabolism. Recent data show that patients admitted to the hospital with high levels of fasting blood glucose are at an increased risk for severe COVID-19 symptoms. Moreover, elevated glucose levels resulted in increased SARS-CoV-2 viral loads in vitro. We believe that healthier habits of diet and exercise, by improving glucose homeostasis could modulate the individual risk of severe COVID-19 symptoms.

Discontinuation of isolation for persons with COVID-19: Is 10 days really safe? (preprint)

BackgroundThe detection of SARS-CoV-2 RNA by real-time polymerase chain reaction (PCR) in respiratory samples from COVID-19 patients is not a direct indication of the presence of viable viruses. The isolation of SARS-CoV-2 in cell culture system however, can acts as surrogate marker of infectiousness. Cell culture based studies performed mostly with hospitalized and moderate/severe COVID-19 claims that no replication competent virus is found after 9 days of the symptoms onset in respiratory samples. Therefore, it is now recommended 10 days isolation before patient discharge. MethodsWe cell-cultured 29 SARS-COV-2 RT-PCR positive respiratory samples at the 10th day after the illness in Vero E6 cells. After two passages, cytopathic effect and cycle threshold (CT) lower than the obtained in the original sample were used to determine positivity. FindingsWe found viable particles in (7/29) 24% of samples tested. The positivity in cell culture was strongly associated (p<0.0001) to the low cycle thresholds in clinical samples (Ct <21). ConclusionThis data adds important knowledge to the current protocols for de-isolation of patients with non-hospitalized mild COVID-19.