Dysglycaemia in Ebola virus disease: a retrospective analysis from the 2018 to 2020 outbreak.

BACKGROUND: Ebola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units. METHODS: We conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC. Glucose measurements were done using a handheld glucometer at the bedside or using the Piccolo xpress Chemistry Analyzer on venous samples. FINDINGS: 384 patients (median age 30 years (interquartile range, IQR, 20-45), 57% female) and 6422 glucose measurements (median 11 per patient, IQR 4-22) were included in the analysis. Severe hypoglycaemia (≤2.2 mmol/L) and hyperglycaemia (>10 mmol/L) were recorded at least once during the ETU admission in 97 (25%) and 225 (59%) patients, respectively. A total of 2004 infusions of glucose-containing intravenous solutions were administered to 302 patients (79%) with a median cumulative dose of 175g (IQR 100-411). The overall case fatality rate was 157/384 (41%) and was 2.2-fold higher (95% CI 1.3-3.8) in patients with severe hypoglycaemia than those without hypoglycaemia (p = 0.0042). In a multivariable Cox proportional hazards model, periods of severe hypoglycaemia (adjusted hazard ratio (aHR) 6.2, 95% CI 3.2-12, p < 0.0001) and moderate hypoglycaemia (aHR 3.0, 95% CI 1.9-4.8, p < 0.0001) were associated with elevated mortality. INTERPRETATION: Hypoglycaemia is common in EVD, requires repeated correction with intravenous dextrose solutions, and is associated with mortality. FUNDING: This study was not supported by any specific funding.

Rhabdomyolysis, Acute Kidney Injury, and Mortality in Ebola Virus Disease: Retrospective Analysis of Cases From the Eastern Democratic Republic of the Congo, 2019.

BACKGROUND: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. METHODS: This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo. RESULTS: An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1-11]). Among patients, 271 (81%) had an elevated CK level (>380 U/L); 202 (61%) had rhabdomyolysis (CK >1000 IU/L); and 45 (14%) had severe rhabdomyolysis (≥5000 U/L). Among survivors, the maximum CK level was a median 1600 (IQR, 550-3400), peaking 3.4 days after admission (IQR, 2.3-5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with a median maximum CK level of 2900 U/L (IQR, 1500-4900). Rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2-3.8]; P = .0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03-2.9]; P = .037). CONCLUSIONS: Rhabdomyolysis is associated with acute kidney injury and mortality in patients with EVD. These findings may inform clinical practice by identifying laboratory monitoring priorities and highlighting the importance of fluid management.

Methodological issues of retrospective surveys for measuring mortality of highly clustered diseases: case study of the 2014-16 Ebola outbreak in Bo District, Sierra Leone.

BACKGROUND: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. OBJECTIVES: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. METHODS: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. RESULTS: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. CONCLUSION: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.

Main findings: For humanitarian organizations it is imperative to document the methodological limitations of cluster surveys and discuss the utility.Added knowledge: This paper adds new knowledge on cluster surveys for highly clustered data such us in Ebola virus disease.Global health impact of policy and action: We provided empirical estimates and discuss design improvements to inform future study.

Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. METHODS: In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. FINDINGS: We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated ≤2 days before onset: 27% [27/99], adjusted relative risk 0·56 [95% CI 0·36-0·82, p=0·0046]; 3-9 days before onset: 20% [28/139], 0·44 [0·29-0·65, p=0·0001]; ≥10 days before onset: 18% [12/68], 0·40 [0·21-0·69; p=0·0022]; vaccination date unknown: 33% [39/117], 0·69 [0·48-0·96; p=0·0341]; and vaccination status unknown: 52% [441/841], 0·80 [0·70-0·91, p=0·0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1·03 [1·02-1·05; p<0·0001]). Cycle threshold values for nucleoprotein were significantly higher-indicating lower viraemia-among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30·0 cycles [IQR 24·6-33·7]) compared with patients who were not vaccinated (21·4 cycles [18·4-25·9], p<0·0001). INTERPRETATION: To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Review: Insights on Current FDA-Approved Monoclonal Antibodies Against Ebola Virus Infection.

The unprecedented 2013-2016 West Africa Ebola outbreak accelerated several medical countermeasures (MCMs) against Ebola virus disease (EVD). Several investigational products (IPs) were used throughout the outbreak but were not conclusive for efficacy results. Only the Randomized Controlled Trial (RCT) on ZMapp was promising but inconclusive. More recently, during the second-largest Ebola outbreak in North Kivu and Ituri provinces, Democratic Republic of the Congo (DRC), four IPs, including one small molecule (Remdesivir), two monoclonal antibody (mAb) cocktails (ZMapp and REGN-EB3) and a single mAb (mAb114), were evaluated in an RCT, the Pamoja Tulinde Maisha (PALM) study. Two products (REGN-EB3 and mAb114) demonstrated efficacy as compared to the control arm, ZMapp. There were remarkably few side effects recorded in the trial. The FDA approved both medications in this scientifically sound study, marking a watershed moment in the field of EVD therapy. These products can be produced relatively inexpensively and can be stockpiled. The administration of mAbs in EVD patients appears to be safe and effective, while several critical knowledge gaps remain; the impact of early administration of Ebola-specific mAbs on developing a robust immune response for future Ebola virus exposure is unknown. The viral mutation escape, leading to resistance, presents a potential limitation for single mAb therapy; further improvements need to be explored. Understanding the contribution of Fc-mediated antibody functions such as antibody-dependent cellular cytotoxicity (ADCC) of those approved mAbs is still critical. The potential merit of combination therapy and post-exposure prophylaxis (PEP) need to be demonstrated. Furthermore, the PALM trial has accounted for 30% of mortality despite the administration of specific treatments. The putative role of EBOV soluble Glycoprotein (sGP) as a decoy to the immune system, the virus persistence, and relapses might be investigated for treatment failure. The development of pan-filovirus or pan-species mAbs remains essential for protection. The interaction between FDA-approved mAbs and vaccines remains unclear and needs to be investigated. In this review, we summarize the efficacy and safety results of the PALM study and review current research questions for the further development of mAbs in pre-exposure or emergency post-exposure use.

The impact of the 2014 Ebola epidemic on HIV disease burden and outcomes in Liberia West Africa.

BACKGROUND: Detailed longitudinal studies of HIV-positive individuals in West Africa are lacking. Here the HIV prevalence, incidence, all-cause mortality, and the proportion of individuals receiving treatment with cART in two cohorts of participants in Ebola-related studies are described. SETTING: Individuals of all ages were enrolled and followed at four sites in the area of Monrovia, Liberia. METHODS: Two cohorts identified in response to the Ebola epidemic are described to provide insights into the current state of the HIV epidemic. HIV testing was performed at baseline for participants in both cohorts and during follow-up in one cohort. RESULTS: Prevalence and incidence of HIV (prevalence of 3.1% for women and 1.4% for men and incidence of 3.3 per 1,000) were higher in these cohorts compared to 2018 national estimates (prevalence of 1.3% and incidence of 0.39 per 1,000). Most participants testing positive did not know their status prior to testing. Of those who knew they were HIV positive, 7.9% reported being on antiretroviral treatment. The death rate among those with HIV was 12.3% compared to 1.9% in HIV-negative individuals (adjusted odds ratio of 6.87). While higher levels of d-dimer were associated with increased mortality, this was not specific to those with HIV, however lower hemoglobin levels were associated with increased mortality among those with HIV. CONCLUSION: These findings point to a need to perform further research studies aimed at fulfilling these knowledge gaps and address current shortcomings in the provision of care for those living with HIV in Liberia.

Comparison of machine learning methods for estimating case fatality ratios: An Ebola outbreak simulation study.

BACKGROUND: Machine learning (ML) algorithms are now increasingly used in infectious disease epidemiology. Epidemiologists should understand how ML algorithms behave within the context of outbreak data where missingness of data is almost ubiquitous. METHODS: Using simulated data, we use a ML algorithmic framework to evaluate data imputation performance and the resulting case fatality ratio (CFR) estimates, focusing on the scale and type of data missingness (i.e., missing completely at random-MCAR, missing at random-MAR, or missing not at random-MNAR). RESULTS: Across ML methods, dataset sizes and proportions of training data used, the area under the receiver operating characteristic curve decreased by 7% (median, range: 1%-16%) when missingness was increased from 10% to 40%. Overall reduction in CFR bias for MAR across methods, proportion of missingness, outbreak size and proportion of training data was 0.5% (median, range: 0%-11%). CONCLUSION: ML methods could reduce bias and increase the precision in CFR estimates at low levels of missingness. However, no method is robust to high percentages of missingness. Thus, a datacentric approach is recommended in outbreak settings-patient survival outcome data should be prioritised for collection and random-sample follow-ups should be implemented to ascertain missing outcomes.

Bundibugyo ebolavirus Survival Is Associated with Early Activation of Adaptive Immunity and Reduced Myeloid-Derived Suppressor Cell Signaling.

Ebolaviruses Bundibugyo virus (BDBV) and Ebola virus (EBOV) cause fatal hemorrhagic disease in humans and nonhuman primates. While the host response to EBOV is well characterized, less is known about BDBV infection. Moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. To explore these knowledge gaps, we transcriptionally profiled BDBV-infected rhesus macaques, a disease model that results in incomplete lethality. This approach enabled us to identify prognostic indicators. As expected, survival (∼60%) correlated with reduced clinical pathology and circulating infectious virus, although peak viral RNA loads were not significantly different between surviving and nonsurviving macaques. Survivors had higher anti-BDBV antibody titers and transcriptionally derived cytotoxic T cell-, memory B cell-, and plasma cell-type quantities, demonstrating activation of adaptive immunity. Conversely, a poor prognosis was associated with lack of an appropriate adaptive response, sustained innate immune signaling, and higher expression of myeloid-derived suppressor cell (MDSC)-related transcripts (S100A8, S100A9, CEBPB, PTGS2, CXCR1, and LILRA3). MDSCs are potent immunosuppressors of cellular and humoral immunity, and therefore, they represent a potential therapeutic target. Circulating plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) levels were also elevated in nonsurvivors and in survivors exhibiting severe illness, emphasizing the importance of maintaining coagulation homeostasis to control disease progression. IMPORTANCE Bundibugyo virus (BDBV) and Ebola virus (EBOV) are ebolaviruses endemic to Africa that cause severe, often fatal hemorrhagic disease. BDBV is considered a less pathogenic ebolavirus due to its reduced lethality during human outbreaks, as well as in experimentally infected nonhuman primates. The reduced mortality of BDBV in NHP models, resulting in a pool of survivors, afforded us the unique opportunity of identifying immune correlates that confer protection against ebolaviruses. In this study, we discovered that the survival of BDBV-infected nonhuman primates (NHPs) was dependent on early development of adaptive (memory) immune responses and reduced myeloid-derived suppressor cell (MDSC)-related signaling. MDSCs are a heterogenous group of immune cells implicated in a number of diseases that are powerful immunosuppressors of cellular and humoral immunity. Thus, MDSCs represent a novel therapeutic target to prevent ebolavirus disease. To our knowledge, this is the first study to link increased morbidity with recruitment of these potent immunosuppressive cells.

A hybrid simulation model to study the impact of combined interventions on Ebola epidemic.

Pandemics have been recognized as a serious global threat to humanity. To effectively prevent the spread and outbreak of the epidemic disease, theoretical models intended to depict the disease dynamics have served as the main tools to understand its underlying mechanisms and thus interrupt its transmission. Two commonly-used models are mean-field compartmental models and agent-based models (ABM). The former ones are analytically tractable for describing the dynamics of subpopulations by cannot explicitly consider the details of individual movements. The latter one is mainly used to the spread of epidemics at a microscopic level but have limited simulation scale for the randomness of the results. To overcome current limitations, a hierarchical hybrid modeling and simulation method, combining mean-field compartmental model and ABM, is proposed in this paper. Based on this method, we build a hybrid model, which takes both individual heterogeneity and the dynamics of sub-populations into account. The proposed model also investigates the impact of combined interventions (i. e. vaccination and pre-deployment training) for healthcare workers (HCWs) on the spread of disease. Taking the case of 2014-2015 Ebola Virus Disease (EVD) in Sierra Leone as an example, we examine its spreading mechanism and evaluate the effect of prevention by our parameterized and validated hybrid model. According to our simulation results, an optimal combination of pre-job training and vaccination deployment strategy has been identified. To conclude, our hybrid model helps informing the synergistic disease control strategies and the corresponding hierarchical hybrid modeling and simulation method can further be used to understand the individual dynamics during epidemic spreading in large scale population and help inform disease control strategies for different infectious disease.

Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.

Ebola virus (EBOV) is a negative single-stranded RNA virus within the Filoviridae family and the causative agent of Ebola virus disease (EVD). Nonhuman primates (NHPs), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of EBOV pathogenesis. However, despite significant genetic similarity (>90%), NHP species display different clinical presentation following EBOV infection, notably a ∼1-2 days delay in disease progression. Consequently, evaluation of therapeutics is generally conducted in rhesus macaques, whereas cynomolgus macaques are utilized to determine efficacy of preventative treatments, notably vaccines. This observation is in line with reported differences in disease severity and host responses between these two NHP following infection with simian varicella virus, influenza A and SARS-CoV-2. However, the molecular underpinnings of these differential outcomes following viral infections remain poorly defined. In this study, we compared published transcriptional profiles obtained from cynomolgus and rhesus macaques infected with the EBOV-Makona Guinea C07 using bivariate and regression analyses to elucidate differences in host responses. We report the presence of a shared core of differentially expressed genes (DEGs) reflecting EVD pathology, including aberrant inflammation, lymphopenia, and coagulopathy. However, the magnitudes of change differed between the two macaque species. These findings suggest that the differential clinical presentation of EVD in these two species is mediated by altered transcriptional responses.

Pathogenicity and Virulence of Ebolaviruses with Species- and Variant-specificity.

Ebola virus (EBOV), belonging to the species Zaire ebolavirus in the genus Ebolavirus, causes a severe febrile illness in humans with case fatality rates (CFRs) up to 90%. While there have been six virus species classified, which each have a single type virus in the genus Ebolavirus, CFRs of ebolavirus infections vary among viruses belonging to each distinct species. In this review, we aim to define the ebolavirus species-specific virulence on the basis of currently available laboratory and experimental findings. In addition, this review will also cover the variant-specific virulence of EBOV by referring to the unique biological and pathogenic characteristics of EBOV variant Makona, a new EBOV variant isolated from the 2013-2016 EBOV disease outbreak in West Africa. A better definition of species-specific and variant-specific virulence of ebolaviruses will facilitate our comprehensive knowledge on genus Ebolavirus biology, leading to the development of therapeutics against well-focused pathogenic mechanisms of each Ebola disease.

The Effect of Ebola Virus Disease on Maternal and Child Health Services and Child Mortality in Sierra Leone, 2014-2015: Implications for COVID-19.

During Sierra Leone's 2014-2015 Ebola virus disease (EVD) epidemic, early reports warned of health system collapse and potential effects on other-cause mortality. These same warnings are reverberating during the COVID-19 pandemic. Consideration of the impacts of EVD on maternal and child health services from facility data can be instructive during COVID-19. We surveyed all peripheral healthcare units (PHUs) in Sierra Leone in October 2014 and March 2015 to assess closures, staffing, amenities, medicines, supplies, and service utilization during May 2014-January 2015 and October 2013-January 2014. We report PHU characteristics and service utilization changes for equivalent 4-month periods during the epidemic and the prior year. We present utilization changes by district and service type, and model excess child mortality. PHU closures (-8%) and staff attrition (-3%) were limited, but many facilities lacked amenities, medicines, and supplies. Utilization of preventive and scheduled services fell more than individualized, clinical care interventions, aside from malaria treatment which declined significantly. Ebola virus disease intensity in districts was weakly associated with utilization, aside from two districts that were severely affected. Modeling suggests utilization declines resulted in 6,782 excess under-five deaths (an increase of 21%) between 2014 and 2015. Ebola virus disease negatively affected service provision, but utilization declined relatively more, particularly for preventive and scheduled interventions. Although these findings are specific to Sierra Leone's EVD epidemic, they illustrate the magnitude of possible effects in other settings due to COVID-19-induced service disruptions, where collateral impacts on child mortality from other preventable causes may far outweigh COVID-19 mortality.

Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care.

BACKGROUND: Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013-2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient-perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. METHODS: Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. RESULTS: The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a 'fatal' outcome to a 'survival' outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence-such as defective interfering genomes. CONCLUSIONS: The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.

Factores pronósticos clínicos determinantes en la supervivencia de pacientes con el virus Ébola / Clinical prognostic factors determining the survival of patients with the Ebola virus

Introducción: La enfermedad por el virus del Ébola presenta una elevada letalidad, por lo cual resulta de gran interés la realización de investigaciones que aborden las manifestaciones clínicas que pudieran ser factores pronósticos de supervivencia. Objetivo: Evaluar factores pronósticos de los pacientes enfermos de ébola. Métodos: El universo lo constituyó la totalidad (n = 350) de pacientes ingresados. Se emplearon medidas de resumen para variables cualitativas, estimaciones puntuales y por intervalos para las cuantitativas, así como las pruebas de significación Kaplan-Meier, regresión de Cox y Odds Ratio. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: La supervivencia global fue del 42,5 por ciento. La media de supervivencia, de aproximadamente 10 días (IC: 9 - 11 días). Los pacientes que ingresaron en estado grave (OR = 3,76), que tuvieron dolor lumbar (OR = 2,24), que refirieron cefalea (OR = 2,22), que presentaron fiebre (OR=2,16), que aquejaron de dolor abdominal (OR=1,95) y a quienes se les constató inyección conjuntival (OR = 1,86), tuvieron mayor probabilidad de fallecer, que quienes ingresaron sin estos síntomas y signos. Conclusiones: La supervivencia fue elevada, pese a las complicaciones presentadas. Los síntomas y signos predictores de muerte en los pacientes fueron: la gravedad del paciente al momento del ingreso, la presencia de dolor lumbar, cefalea, fiebre, dolor abdominal e inyección conjuntival(AU)

Introduction: Ebola virus disease has a high lethality, which is why it is of great interest to carry out research that addresses clinical manifestations that could be prognostic factors for survival. Objective: To evaluate prognostic factors of Ebola patients. Methods: the universe was constituted by the totality (n = 350) of admitted patients. Summary measures were used for qualitative variables, point and interval estimates for quantitative variables, as well as Kaplan-Meier significance tests, Cox regression and Odds Ratio. We worked with a 95% level of reliability. Results: The overall survival was 42.5 por ciento. The average survival, approximately 10 days (CI: 9-11 days). Patients who were admitted in serious condition (OR = 3.76), who had low back pain (OR = 2.24), who reported headache (OR = 2.22), who presented fever (OR = 2.16), who they suffered from abdominal pain (OR = 1.95) and who were found to have conjunctival injection (OR = 1.86), were more likely to die than those who entered without these symptoms and signs. Conclusions: Survival was high, despite the complications presented. The symptoms and predictive signs of death in the patients were: the severity of the patient at admission, the presence of low back pain, headache, fever, abdominal pain and conjunctival injection(AU)

Remdesivir against COVID-19 and Other Viral Diseases.

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.

National reporting of deaths after enhanced Ebola surveillance in Sierra Leone.

BACKGROUND: Sierra Leone experienced the largest documented epidemic of Ebola Virus Disease in 2014-2015. The government implemented a national tollfree telephone line (1-1-7) for public reporting of illness and deaths to improve the detection of Ebola cases. Reporting of deaths declined substantially after the epidemic ended. To inform routine mortality surveillance, we aimed to describe the trends in deaths reported to the 1-1-7 system and to quantify people's motivations to continue reporting deaths after the epidemic. METHODS: First, we described the monthly trends in the number of deaths reported to the 1-1-7 system between September 2014 and September 2019. Second, we conducted a telephone survey in April 2017 with a national sample of individuals who reported a death to the 1-1-7 system between December 2016 and April 2017. We described the reported deaths and used ordered logistic regression modeling to examine the potential drivers of reporting motivations. FINDINGS: Analysis of the number of deaths reported to the 1-1-7 system showed that 12% of the expected deaths were captured in 2017 compared to approximately 34% in 2016 and over 100% in 2015. We interviewed 1,291 death reporters in the survey. Family members reported 56% of the deaths. Nearly every respondent (94%) expressed that they wanted the 1-1-7 system to continue. The most common motivation to report was to obey the government's mandate (82%). Respondents felt more motivated to report if the decedent exhibited Ebola-like symptoms (adjusted odds ratio 2.3; 95% confidence interval 1.8-2.9). CONCLUSIONS: Motivation to report deaths that resembled Ebola in the post-outbreak setting may have been influenced by knowledge and experiences from the prolonged epidemic. Transitioning the system to a routine mortality surveillance tool may require a robust social mobilization component to match the high reporting levels during the epidemic, which exceeded more than 100% of expected deaths in 2015.

Severity score for predicting in-facility Ebola treatment outcome.

PURPOSE: Sierra Leone recorded the highest incidence rate for the 2013-2016 West African Ebola outbreak. In this investigation, we used the medical records of Ebola patients with different sociodemographic and clinical features to determine the factors that are associated with Ebola treatment outcome during the 2013-2016 West African Ebola outbreak in Sierra Leone and constructed a predictive in-facility mortality score. METHODS: We used the anonymized medical records of 1077 laboratory-confirmed pediatric and adult patients with EVD who received treatment at the 34 Military Hospital and the Police Training School Ebola Treatment Centers in Sierra Leone between the period of June 2014 and April 2015. We later determined the in-facility case fatality rates for Ebola, the odds of dying during Ebola treatment, and later constructed a predictive in-facility mortality score for these patients based on their clinical and sociodemographic characteristics. RESULTS: We constructed a model that partitioned the study population into three mortality risk groups of equal patient numbers, based on risk scoring: low (score ≤ -5), medium (score -4 to 1), and high-risk group (score ≥ 2). The CFR of patients with EVD belonging to the low- (≤-5), medium (-4 to 1), and high- (≥2) risk groups were 0.56%, 9.75%, and 67.41%, respectively. CONCLUSIONS: We succeeded in designing an in-facility mortality risk score that reflects EVD clinical severity and can assist in the clinical prioritization of patients with EVD.