Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis.

BACKGROUND: Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539. FINDINGS: We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one. INTERPRETATION: REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks. FUNDING: WHO.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease.

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018-2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 - 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22-70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Clinical presentation, outcomes and factors associated with mortality: A prospective study from three COVID-19 referral care centres in West Africa.

OBJECTIVES: The overall death toll from COVID-19 in Africa is reported to be low but there is little individual-level evidence on the severity of the disease. This study examined the clinical spectrum and outcome of patients monitored in COVID-19 care centres (CCCs) in two West-African countries. METHODS: Burkina Faso and Guinea set up referral CCCs to hospitalise all symptomatic SARS-CoV-2 carriers, regardless of the severity of their symptoms. Data collected from hospitalised patients by November 2020 are presented. RESULT: A total of 1,805 patients (64% men, median age 41 years) were admitted with COVID-19. Symptoms lasted for a median of 7 days (IQR 4-11). During hospitalisation, 443 (25%) had a SpO2 < 94% at least once, 237 (13%) received oxygen and 266 (15%) took corticosteroids. Mortality was 5% overall, and 1%, 5% and 14% in patients aged <40, 40-59 and ≥60 years, respectively. In multivariable analysis, the risk of death was higher in men (aOR 2.0, 95% CI 1.1; 3.6), people aged ≥60 years (aOR 2.9, 95% CI 1.7; 4.8) and those with chronic hypertension (aOR 2.1, 95% CI 1.2; 3.4). CONCLUSION: COVID-19 is as severe in Africa as elsewhere, and there must be more vigilance for common risk factors such as older age and hypertension.