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Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU., Competing Interests: Conflict of interest: L.F. Reyes has nothing to disclose. Conflict of interest: S. Murthy declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research. Conflict of interest: E. Garcia-Gallo has nothing to disclose. Conflict of interest: M. Irvine has nothing to disclose. Conflict of interest: L. Merson has nothing to disclose. Conflict of interest: I. Martin-Loeches declares consulting fees for Gilead outside of the submitted work. Conflict of interest: J. Rello has nothing to disclose. Conflict of interest: F.S. Taccone has nothing to disclose. Conflict of interest: R.A. Fowler has nothing to disclose. Conflict of interest: A.B. Docherty has nothing to disclose. Conflict of interest: C. Kartsonaki has nothing to disclose. Conflict of interest: I. Aragao has nothing to disclose. Conflict of interest: P.W. Barrett has nothing to disclose. Conflict of interest: A. Beane has nothing to disclose. Conflict of interest: A. Burrell has nothing to disclose. Conflict of interest: M.P. Cheng has nothing to disclose. Conflict of interest: M.D. Christian has nothing to disclose. Conflict of interest: J.P. Cidade has nothing to disclose. Conflict of interest: B.W. Citarella has nothing to disclose. Conflict of interest: C.A. Donnelly has nothing to disclose. Conflict of interest: S.M. Fernandes has nothing to disclose. Conflict of interest: C. French has nothing to disclose. Conflict of interest: R. Haniffa has nothing to disclose. Conflict of interest: E.M. Harrison has nothing to disclose. Conflict of interest: A.Y.W. Ho declares grant funding from Medical Research Council UK, Scottish Funding Council – Grand Challenges Research Fund and the Wellcome Trust, outside this submitted work. Conflict of interest: M. Joseph has nothing to disclose. Conflict of interest: I. Khan has nothing to disclose. Conflict of interest: M.E. Kho has nothing to disclose. Conflict of interest: A.B. Kildal has nothing to disclose. Conflict of interest: D. Kutsogiannis declares personal fees for a lecture from Tabuk Pharmaceuticals and the Saudi Critical Care Society. Conflict of interest: F. Lamontagne has nothing to disclose. Conflict of interest: T.C. Lee declares research salary support from les Fonds de recherche du Québec – Santé. Conflict of interest: G.L. Bassi has nothing to disclose. Conflict of interest: J.W. Lopez Revilla has nothing to disclose. Conflict of interest: C. Marquis has nothing to disclose. Conflict of interest: J. Millar has nothing to disclose. Conflict of interest: R. Neto has nothing to disclose. Conflict of interest: A. Nichol declares a grant from the Health Research Board of Ireland to support data collection in Ireland (CTN-2014-012). Conflict of interest: R. Parke has nothing to disclose. Conflict of interest: R. Pereira has nothing to disclose. Conflict of interest: S. Poli has nothing to disclose. Conflict of interest: P. Povoa declares personal fees (for lectures and advisory boards) from MSD, Technophage, Sanofi and Gilead. Conflict of interest: K. Ramanathan has nothing to disclose. Conflict of interest: O. Rewa declares consulting fees from Baxter Inc. Conflict of interest: J. Riera has nothing to disclose. Conflict of interest: S. Shrapnel participated as an investigator for an observational study analysing intensive care unit patients with COVID-19 (for the Critical Care Consortium including ECMOCARD) funded by The Prince Charles Hospital Foundation during the conduct of this study. S. Shrapnel reports in kind support from the Australian Research Council Centre of Excellence for Engineered Quantum Systems (CE170100009). Conflict of interest: M.J. Silva has nothing to disclose. Conflict of interest: A. Udy has nothing to disclose. Conflict of interest: T. Uyeki has nothing to disclose. Conflict of interest: S.A. Webb has nothing to disclose. Conflict of interest: E-J. Wils has nothing to disclose. Conflict of interest: A. Rojek has nothing to disclose. Conflict of interest: P.L. Olliaro has nothing to disclose., (Copyright ©The authors 2022.)

Background: There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics., Methods: We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay., Results: Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors., Conclusions: Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation., Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Competing Interests: MH, JB, GC, BC, AD, ED, CD, JD, ME, CK, LM, MP, JW, PH, AR, PO No competing interests declared, (© 2021, ISARIC Clinical Characterisation Group et al.)

Background: In Australia, COVID-19 diagnosis relies on RT-PCR testing which is relatively costly and time-consuming. To date, few studies have assessed the performance and implementation of rapid antigen-based SARS-CoV-2 testing in a setting with a low prevalence of COVID-19 infections, such as Australia., Methods: This study recruited participants presenting for COVID-19 testing at three Melbourne metropolitan hospitals during a period of low COVID-19 prevalence. The Abbott PanBio TM COVID-19 Ag point-of-care test was performed alongside RT-PCR. In addition, participants with COVID-19 notified to the Victorian Government were invited to provide additional swabs to aid validation. Implementation challenges were also documented., Findings: The specificity of the Abbott PanBio TM COVID-19 Ag test was 99.96% (95% CI 99.73 - 100%). Sensitivity amongst participants with RT-PCR-confirmed infection was dependent upon the duration of symptoms reported, ranging from 77.3% (duration 1 to 33 days) to 100% in those within seven days of symptom onset. A range of implementation challenges were identified which may inform future COVID-19 testing strategies in a low prevalence setting., Interpretation: Given the high specificity, antigen-based tests may be most useful in rapidly triaging public health and hospital resources while expediting confirmatory RT-PCR testing. Considering the limitations in test sensitivity and the potential for rapid transmission in susceptible populations, particularly in hospital settings, careful consideration is required for implementation of antigen testing in a low prevalence setting., Funding: This work was funded by the Victorian Department of Health and Human Services. The funder was not involved in data analysis or manuscript preparation., Competing Interests: SL reports grants from National Institutes of Health (NIH), grants from American Foundation for AIDS Research (amfAR), grants from Gilead Sciences, grants from Merck, grants from ViiV, grants from Leidos, grants from Wellcome Trust, grants from Australian Centre for HIV and Hepatitis Virology Research (ACH2), grants from Melbourne HIV Cure Consortium, grants from Victorian Department of Health and Human Services (DHHS), grants from Medical Research Future Fund (MRFF), outside the submitted work. KG reports grants from Royal Australasian Society of Physicians (RACP), grants from Murdoch Children's Research Institute (MCRI), other from Isabel & John Gilbertson Charitable Trust, grants from Department of Health and Human Services (DHHS) Victoria, outside the submitted work., (© 2021 The Author(s). Published by Elsevier Ltd.)

Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks-including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'., (© 2017 The Authors.)

The outbreak of Ebola virus disease (EVD) that occurred from 2013 to 2016 in the West African countries of Guinea, Liberia, and Sierra Leone, with imported cases to three neighboring African countries as well as to the United States and Europe, constituted a major humanitarian disaster. The outbreak numbered over 28,500 cases, more than 10 times the number cumulatively registered from all previous EVD outbreaks combined, with at least 11,000 deaths, and resulted in billions of dollars of lost economic growth to an already impoverished region. The unprecedented scale of West Africa 2013 took the world by surprise and laid bare deficiencies in our response capacity to complex humanitarian disasters of highly infectious and lethal pathogens. However, the magnitude of West Africa 2013 also provided an, albeit unwelcome, unique opportunity and obligation to better understand the biology and epidemiology of EVD and, equally as important, the many scientific, economic, social, political, ethical, and logistical challenges in confronting emerging diseases in the modern era. Here we re-examine EVD, reviewing the unique challenges and scientific advances of West Africa 2013, contrasting them with the prior assumptions and classical teachings, identifying what they have taught us and what we still have to learn.