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Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. Methods With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. Results Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41–2.13; P Conclusions The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.

Antibodies predating infection Immunological memory after infection with seasonal human coronaviruses (hCoVs) may potentially contribute to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ng et al. report that in a cohort of 350 SARS-CoV-2–uninfected individuals, a small proportion had circulating immunoglobulin G (IgG) antibodies that could cross-react with the S2 subunit of the SARS-CoV-2 spike protein (see the Perspective by Guthmiller and Wilson). By contrast, COVID-19 patients generated IgA, IgG, and IgM antibodies that recognized both the S1 and S2 subunits. The anti-S2 antibodies from SARS-CoV-2–uninfected patients showed specific neutralizing activity against both SARS-CoV-2 and SARS-CoV-2 S pseudotypes. A much higher percentage of SARS-CoV-2–uninfected children and adolescents were positive for these antibodies compared with adults. This pattern may be due to the fact that children and adolescents generally have higher hCoV infection rates and a more diverse antibody repertoire, which may explain the age distribution of COVID-19 susceptibility. Science, this issue p. 1339; see also p. 1272, SARS-CoV-2 neutralizing antibodies can be found in some uninfected individuals—predominantly children and adolescents., Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)–reactive antibodies were detectable using a flow cytometry–based method in SARS-CoV-2–uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S–reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2–uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.

COVID-19, caused by SARS-CoV-2, is an emerging viral respiratory pathogen. The disease was first described in China in 2019, likely emerging as a zoonosis, before spreading worldwide to cause a severe global pandemic in 2020. COVID-19 is transmitted person to person, predominantly by droplet spread. COVID-19 causes a wide spectrum of clinical illness ranging from asymptomatic infection, to a mild self-limiting illness. A small proportion of individuals will go on to develop a more severe respiratory illness which may be complicated by acute respiratory distress syndrome. The majority of individuals will make a full recovery but a minority of patients will have a more severe outcome. Age is the strongest predictor of outcomes with mortality increasing to 15% or higher among those aged 80 years or older. Treatment options for COVID-19 continue to evolve. The strongest current evidence is the use of systemic corticosteroids which reduce mortality in patients with moderate to severe COVID-19. Given the epidemic nature of COVID-19 early surge planning and expansion of both staff and bed base capacity are critical. At the time of writing a number of promising COVID-19 vaccines have been developed but the long term impact of these vaccines on the pandemic is uncertain.

Background: A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. Methods: This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [aβ2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I β2GPI (aD1β2GPI) IgG. Findings: There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p

Monkeypox is a rare viral zoonotic disease. The causing virus belongs to the Orthopoxvirus genus that includes variola virus (the cause of smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. There are two distinct clades of monkeypox virus—Central African and West African. The first human cases were identified in the Democratic Republic of Congo in 1970 [1]. Outside of Africa, cases of human monkeypox infections have been documented in four countries: four cases the United Kingdom (UK) in 2018/2019, one case in Israel in 2018 and one case in Singapore in 2019 [2], 47 cases in the United States (US) in 2003 and one in 2021 [3]. We report on a family cluster of three recent cases of monkeypox in the UK associated with travel from Nigeria.

Supplemental Digital Content is available in the text., OBJECTIVES: Multiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease. DESIGN: A search of ClinicalTrials.gov identified coronavirus disease 2019 immunological drug targets. We subsequently conducted a retrospective observational cohort study investigating the association of serum biomarkers within the first 5 days of hospital admission relating to putative therapeutic biomarkers with illness severity and outcome. SETTING: University College London, a tertiary academic medical center in the United Kingdom. PATIENTS: Patients admitted to hospital with a diagnosis of coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-six patients were recruited, 44 (51%) with mild disease and 42 (49%) with severe disease. We measured levels of 10 cytokines/signaling proteins related to the most common therapeutic targets (granulocyte-macrophage colony-stimulating factor, interferon-α2a, interferon-β, interferon-γ, interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-7, interleukin-8, tumor necrosis factor-α), immunoglobulin G antibodies directed against either coronavirus disease 2019 spike protein or nucleocapsid protein, and neutralization titers of antibodies. Four-hundred seventy-seven randomized trials, including 168 different therapies against 83 different pathways, were identified. Six of the 10 markers (interleukin-6, interleukin-7, interleukin-8, interferon-α2a, interferon-β, interleukin-1 receptor antagonist) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable spike protein or nucleocapsid protein immunoglobulin G antibodies with equivalent levels between groups. Neutralization titers were higher among patients with severe disease. CONCLUSIONS: Some therapeutic and prognostic biomarkers may be useful in identifying coronavirus disease 2019 patients who may benefit from specific immunomodulatory therapies, particularly interleukin-6. However, biomarker absolute values often did not discriminate between patients with mild and severe disease or death, implying that these immunomodulatory treatments may be of limited benefit.

Background:The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood.Methods:We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity.Results:Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection.Conclusions:The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric.Funding:This work was supported by the Francis Crick Institute and the Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg.

BackgroundThe SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the UK National Health Service (NHS). During the first wave of SARS-CoV-2 transmission in UK, SARS-CoV-2 NHS diagnostic test availability was limited to self-isolating symptomatic staff. The burden of symptomatic and asymptomatic infection in healthcare workers (HCW) attending work was unknown.MethodsWe conducted an observational cohort study of SARS-CoV-2 infection in HCW working in an acute NHS Trust during the first wave of the COVID-19 pandemic, using serial self-collected saliva and nasopharyngeal (NP) samples. We also collected self-assessed symptom profiles and isolation behaviours. We retrospectively compared SARS-CoV-2 detection by RT-PCR from saliva (weekly) and NP swabs (twice weekly) from 85 individuals in this cohort and evaluated the association with symptoms.FindingsOver a 12-week period from 30th March 2020, 40% (n=34/85, CI95% 31.3-51.8%) HCWs had evidence of SARS-CoV-2 infection by surveillance NP swab and/or saliva RT-qPCR. Agreement between paired saliva and NP swabs was poor (28.6%, CI95% 13.2-48.7%) with both methods detecting symptomatic and asymptomatic infections. Symptoms were reported by 47.1% (n=40) and self-isolation by 25.9% participants (n=22). Only 41.2% (n=14/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of the infection.InterpretationHCWs are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections in HCW. Saliva is an easily accessible fluid sample for screening for SARS-CoV-2 infection and in addition to NP swab, facilitated ascertainment of symptomatic and asymptomatic cases in this setting. Combined saliva and NP testing would improve detection of SARS-CoV-2 for surveillance. Better understanding of transmissibility from asymptomatic staff using transmission-based infection precautions, is required to inform policy.

There are over 200 herpesvirus species, of which 10 affect humans. Each of these 10 herpesviruses has a unique clinical syndrome, but common to all is their ability to cause infection and pathology in the central nervous system. In this article, we discuss the epidemiology, clinical presentation, diagnostic modalities, treatment, sequelae, and availability of vaccination of each of the following herpesviruses: herpes simplex virus 1 and 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6A, 6B, and 7, Epstein–Barr virus, human herpesvirus 8, and simian herpesvirus B.

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy., Graphical Abstract, This study describes neutralization by antibodies and convalescent sera of SARS-CoV-2 spike mutants. Rees-Spear et al. show that SARS-CoV amino acid substitutions and the B.1.1.7 variant can block monoclonal antibody neutralization and that serum samples collected following mild illness are less resilient to spike variation than those following severe illness.

We examined the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 that arose in the United Kingdom and spread globally. Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa B.1.351 variant, than of the infecting variant. The drop in cross-reactivity was more pronounced following B.1.1.7 than parental strain infection, indicating asymmetric heterotypic immunity induced by SARS-CoV-2 variants.

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterised neurological syndromes involving the peripheral and central nervous system (n = 34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n = 94) and without (n = 24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with central nervous system inflammation (encephalitis and acute disseminated encephalomyelitis) (14800pg/mL [400, 32400]), compared to those with encephalopathy (1410pg/mL [756, 1446], peripheral syndromes (GBS) (740pg/mL [507, 881]) and controls (872pg/mL [654,1200]). Serum neurofilament light levels were elevated across patients hospitalised with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19., Graphical Abstract Graphical Abstract

Background: For a targeted therapeutic strategy to show outcome benefit, there needs to be a strong biological and pathogenic rationale to underpin and direct personalised treatments. Relevant biological disease features and biomarkers identify patients for the correct therapeutic, delivered at an appropriate time, dose and duration for maximal efficacy. We evaluated whether serum levels of a wide range of proposed therapeutic targets in COVID-19 discriminated between patients with mild and severe disease or death. Methods: A search of clinicaltrials.gov identified immunological drug targets in COVID-19. We subsequently conducted an observational study investigating the association of serum biomarkers relating to putative therapeutic biomarkers with illness severity and outcome. Results: A search of clinicaltrials.gov identified 477 randomized trials assessing immunomodulatory therapies, including 168 different therapies against 83 different pathways. We measured levels of ten cytokines/signalling proteins including those related to the most common therapeutic targets (GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1ra, IL-6, IL-7, IL-8, TNF-α), immunoglobulin G ( IgG) antibodies directed against either the COVID-19 spike protein (S1) or nucleocapsid protein (N), and neutralization titres of antibodies within the first 5 days of hospital admission in 86 patients, 44 (51%) with mild disease and 42 (49%) with severe disease. Six of the ten cytokine/signalling protein markers measured (IL-6, IL-7, IL-8, interferon- a, interferon- b, IL -1ra ) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable S1 or N IgG antibodies with equivalent levels between groups. Neutralization titres were higher among patients with severe disease. Interpretation: Some therapeutic and prognostic biomarkers may be potentially useful in identifying patients who may benefit from specific immunomodulatory therapies in COVID-19 disease, particularly interleukin-6. It is however noteworthy that absolute values of a number of identified biomarkers were either appropriately elevated or within the normal range. This implies that these immunomodulatory treatments may be of limited benefit. Funding: National Institute for Health Research UCLH Biomedical Research Centre (BRC756/HI/MS/101440) and the UCL Coronavirus Response Fund. Declaration of Interests: MeS reports grants and advisory board fees from NewB, grants from the Defence Science and Technology Laboratory, Critical Pressure, Apollo Therapeutics, advisory board and speaker fees (paid to his institution) from Amormed, Biotest, GE, Baxter, Roche, and Bayer, and honorarium for chairing a data monitoring and safety committee from Shionogi. All other authors have nothing to declare. Ethics Approval Statement: Ethical approval was received from the London-Westminster Research Ethics Committee, the Health Research Authority and Health and Care Research Wales (HCRW) on 2nd July 2020 (REC reference 20/HRA/2505, IRAS ID 284088). The SAFER study protocol was approved by the NHS Health Research Authority (ref 20/SC/0147) on 26 March 2020. Ethical oversight was provided by the South- Central Berkshire Research Ethics Committee.

Background: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raise concerns pertinent to the current mass vaccination campaigns and use of monoclonal antibodies. We describe emergence of the variant of concern (VOC) B.1.1.7 in two North Central London (NCL) hospitals including virological characteristics and clinical severity in contemporaneous patients with and without the new variant. The strength of our study is the depth and granularity of clinical data. Methods: SARS-CoV-2 PCR positive samples collected from 9th November 2020 for patients acutely admitted to one of 2 NCL hospitals on or before 20th December 2020 were sequenced and analysed for the presence of VOC-defining mutations. We compared illness severity in those with variant of concern (VOC) and non-VOC infections and conducted supplementary genomic analyses in a cohort of chronically shedding immunocompromised/treated patients. Viral loads were compared by Ct value and sequencing read-depth. Findings: Of 341 successfully sequenced patients, 198 (58%) had VOC infections. There was no evidence of an association with severe disease by lineage (VOC vs non-VOC) in unadjusted analyses (PR 0.97, 95% CI 0.72-1.31), or analyses adjusted for sex, age, comorbidities and ethnicity (aPR 1.07, 95% CI 0.79-1.43). We detected no VOC-defining mutations in immunocompromised/treated patients; viral loads were higher in VOC samples. Interpretation: Despite emerging evidence of increased transmissibility of the VOC, we did not identify an association with severe disease, suggesting the surge in hospitalisations was more likely related to a significant increase in cases overall rather than virus characteristics. Funding Statement: UCLH APDU receives funding from the University College London Hospitals NHS Trust. DF was funded by the i-sense EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (EP/R00529X/1). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The clinical information and SARS-CoV-2 PCR samples were collected as part of routine clinical care. Data were extracted and analysed using permission granted by the NHS REC (IRAS:284088, REC reference:20/HRA/2505).

BackgroundODK provides software and standards that are popular solutions for off-grid electronic data collection and are the basis of related products like CommCare, Enketo, Ona, SurveyCTO and KoBoToolbox. In combination with the use of statistical analysis software such as R, these tools provide fully open-source options for off-grid use in public health data collection, management, analysis and reporting.ResultsNew functions were developed to facilitate the use of ODK, Enketo and R in large scale data collection, aggregation, monitoring and near-real-time analysis during clinical research in health emergencies. We present open-source enhancements to ODK that include a built-in audit-trail, a framework and companion app for biometric registration of ISO/IEC 19794-2 fingerprint templates, enhanced performance features, better scalability for studies featuring millions of data form submissions, increased options for parallelisation of research projects, and pipelines for automated management and analysis of data. We also developed novel encryption protocols for enhanced web-form security in Enketo. During the 2018-2020 Ebola epidemic in the North Kivu & Ituri regions of Democratic Republic of Congo, ODK, Enketo and R were leveraged to support the DRC Ministère de la Santé RDC and World Health Organization in their efforts to administer an experimental vaccine (VSV-Zebov-GP) as part of their strategy to control the transmission of infection. Against the backdrop of a complex and challenging epidemic response, our enhanced platform of open tools was used to collect and manage data from more than 280,000 eligible study participants who received VSV under informed consent. These data were used to determine whether the VSV-Zebov-GP was safe and effective and to guide daily field operations.ConclusionsWe present open source developments that make electronic data management during clinical research and health emergencies more viable and robust. These developments will also enhance and expand the functionality of a diverse range of data collection platforms (Ona, KoBoToolbox etc.) that are based on the ODK software and standards.FundingThis research is funded by the Department of Health and Social Care using UK Aid funding and is managed by the NIHR (PR-OD-1017-20001).

ObjectivesCOVID-19 is spreading in long-term care facilities with devastating outcomes worldwide, especially for people with chronic health conditions. There is a pressing need to adopt effective measures prevention and containment of in such settings.DesignRetrospective cohort study assessing the effect of enhanced surveillance and early preventative strategies and comparing outcomes for people with severe epilepsy and other comorbiditiesSettingThree long-term care facilities: Chalfont Centre for Epilepsy (CCE), St. Elisabeth (STE), and The Meath (TM) with different models of primary and specialist care involvement, in the United KingdomParticipants286 long-term residents (age range 19–91 years), 740 carers who had been in contact with the residents during the observation period between 16 March and 05 June 2020.InterventionsEarly preventative and infection control measures with identification and isolation of symptomatic cases, with additional enhanced surveillance and isolation of asymptomatic residents and carers at one site (CCE)Main outcome measuresInfection rate for SARS-CoV-2 among residents and carers, asymptomatic rate and case fatality rate, if available.ResultsDuring a 12-week observation period, we identified 29 people (13 residents) who were SARS-CoV-2 positive with confirmed outbreaks amongst residents in two long-term care facilities (CCE, STE). At CCE, two out of 98 residents were symptomatic and tested positive, one of whom died. A further seven individuals testing positive on weekly enhanced surveillance had a completely asymptomatic course. One asymptomatic carer tested positive after contact with confirmed COVID-19 patients in another institution. Since 30 April 2020, during on-site weekly enhanced surveillance all 275 caregivers tested repeatedly negative. At STE, three out of 146 residents were symptomatic and tested positive, a fourth tested positive during hospital admission for symptoms not related to COVID-19. Since April 6, 2020, 105/215 carers presenting with typical symptoms for COVID-19 were tested, of whom 15 tested positive. At TM, testing of symptomatic carers only started from early/mid-April, whilst on-site testing, even of symptomatic residents, was not available until recently.During the observation period, eight of 80 residents were symptomatic but none was tested. Twenty-six of 250 carers were symptomatic and were tested, of whom two tested positive.ConclusionsInfection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic cases are identified through enhanced surveillance at individual and care staff level. We observed a low rate of morbidity and mortality which confirmed that preventative measures with isolation of suspected and confirmed cases of COVID-19 can reduce resident-to-resident and reverse resident-to-carer transmission.

Background SARS-CoV-2 infection in Healthcare Workers (HCWs) is a public health concern during the pandemic. Little description has been made of their antibody response over time in the presence or absence detectable SARS-CoV-2 RNA and of symptoms. We followed a cohort of patient-facing HCWs at an acute hospital in London to measure seroconversion and RNA detection at the peak of the pandemic in London. Methods We enrolled 200 front-line HCWs between 26 March and 8 April 2020 and collected twice-weekly self-administered nose and throat swabs and monthly blood samples. Baseline and regular symptom data were also collected. Swabs were tested for SARS-CoV-2 RNA by polymerase chain reaction, and serum for IgM, IgA and IgG antibodies to the virus spike protein by enzyme-linked immunosorbent assay and flow cytometry. Findings We enrolled HCWs with a variety of roles who worked in areas where COVID-19 patients were admitted and cared for. During the first month of observation, 42/200 (21%) HCWs were PCR positive in at least one nose and throat swab. Only 8/42 HCW (19%) who were PCR positive during the study period had symptoms that met the current case definition. Of 181 HCWs who provided enrollment and follow-up blood samples, 82/181 (45.3%) were seropositive; 36/181 (19.9%) seroconverted during the study and 46/181 (25.4%) were seropositive at both time points. In 33 HCWs who had positive serology at baseline but were PCR negative, 32 remained PCR negative throughout follow-up. One HCW had a PCR positive swab six days after enrollment, likely representing a waning infection. Interpretation The extremely high seropositivity and RNA detection in this cohort of front-line HCWs who worked during the peak of the pandemic brings policies to protect staff and patients in the hospital environment into acute focus. Our findings have implications for planning for the expected second wave and for future vaccination roll out campaigns in similar settings. The further evidence of asymptomatic SARS-CoV-2 infection indicates that asymptomatic surveillance of HCWs is essential while our study sets the foundations to answer pertinent questions around the duration of protective immune response and the risk of re-infection.

Coronavirus disease 2019 (COVID-19) can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66 of 435 (15%) COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures.

Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.

The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.

Background Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Methods Sera were collected from JIA (n=118), JDM (n=49) and JSLE (n=30) patients, and from healthy control (n=54) children and adolescents, prior to the coronavirus disease-19 (COVID-19) pandemic. We employed sensitive flow cytometry-based assays to determine titres of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and compared with respective titres in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). Findings Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients maintained comparable or stronger humoral responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Conclusions Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies., Graphical Abstract, Deakin, Cornish et al. examined the antibody response to the common-cold coronavirus, HCoV-OC43, and cross-reactive response to SARS-CoV-2 in pre-COVID-19 pandemic sera from JIA, JDM and JSLE patients. They found that these prevalent inflammatory rheumatic diseases or their immunosuppressive treatment did not adversely affect the response to a common-cold coronavirus.

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), millions have been diagnosed with COVID-19. The major clinical manifestations of SARS-CoV-2 infection are pulmonary, however reports of COVID-19-associated central nervous system complications emerged.1 2 We report a case of encephalitis in a pulmonologically asymptomatic patient with COVID-19. A 66-year-old female presented in mid-March 2020, with a few hours history of confusion. She was completely well until the day of admission. There was no medical, infectious or behavioural prodrome. There was no alcohol or nutritional history. She had travelled to Spain, the USA and Mexico in the 3 months prior, but had been home for 19 days. She suddenly complained that her head ‘felt funny’. She carried on normal tasks but, within an hour, became confused, amnestic and was unaware of why social distancing measures were being observed. On admission, her temperature was 37.9°C. Other observations were normal. She was lymphopaenic at 0.4×109/L (0.8–3.1). Full blood count was otherwise normal. C-reactive protein (CRP) was 14.5 mg/L (0–5). Routine blood tests, including renal function, liver function and clotting, were normal. A brain CT was unremarkable. Six hours after admission, she had a single, spontaneously resolving, generalised tonic-clonic seizure. Her postictal Glasgow Coma Scale (GCS) was 6/15 (E1/V1/M4). This remained unchanged for 48 hours. Postictal neurological examination showed equal, reactive pupils, no response to visual menace, no vestibulo-ocular reflex, normal tone bilaterally, symmetrical brisk reflexes and extensor plantars. She remained febrile (37.9°C) for 48 hours. Oxygen saturation dropped to 93% on air only once during her 4-week admission. She never developed breathlessness, cough or tachypnoea. An MRI of the brain on day 2 showed non-enhancing, symmetrical T2 and FLAIR …

BACKGROUND: While a number of predictors for Ebola mortality have been identified, less is known about post-viral symptoms. The identification of acute-illness predictors for post-viral symptoms could allow the selection of patients for more active follow up in the future, and those in whom early interventions may be beneficial in the long term. Studying predictors of both mortality and post-viral symptoms within a single cohort of patients could also further our understanding of the pathophysiology of survivor sequelae.METHODS/PRINCIPAL FINDINGS: We performed a historical cohort study using data collected as part of routine clinical care from an Ebola Treatment Centre (ETC) in Kerry Town, Sierra Leone, in order to identify predictors of mortality and of post-viral symptoms. Variables included as potential predictors were sex, age, date of admission, first recorded viral load at the ETC and symptoms (recorded upon presentation at the ETC). Multivariable logistic regression was used to identify predictors. Of 263 Ebola-confirmed patients admitted between November 2014 and March 2015, 151 (57%) survived to ETC discharge. Viral load was the strongest predictor of mortality (adjusted OR comparing high with low viral load: 84.97, 95% CI 30.87-345.94). We did not find evidence that a high viral load predicted post-viral symptoms (ocular: 1.17, 95% CI 0.35-3.97; musculoskeletal: 1.07, 95% CI 0.28-4.08). Ocular post-viral symptoms were more common in females (2.31, 95% CI 0.98-5.43) and in those who had experienced hiccups during the acute phase (4.73, 95% CI 0.90-24.73).CONCLUSIONS/SIGNIFICANCE: These findings may add epidemiological support to the hypothesis that post-viral symptoms have an immune-mediated aspect and may not only be a consequence of high viral load and disease severity.

Background The 2014–2016 West Africa Ebola epidemic highlighted the difficulty of collecting patient information during emergencies, especially in highly infectious environments. Health information systems (HISs) appropriate for such settings were lacking prior to this outbreak. Here we describe our development and implementation of paper and electronic HISs at the Sierra Leone Kerry Town Ebola treatment centre (ETC) from 2014 to 2015. We share our approach, experiences, and recommendations for future health emergencies. Methods We developed eight fact-finding questions about data-related needs, priorities, and restrictions at the ETC (“inputs”) to inform eight structural decisions (“outputs”) across six core HIS components. Semi-structured interviews about the “inputs” were then conducted with HIS stakeholders, chosen based on their teams’ involvement in ETC HIS-related activities. Their responses were used to formulate the “output” results to guide the HIS design. We implemented the HIS using an Agile approach, monitored system usage, and developed a structured questionnaire on user experiences and opinions. Results Some key “input” responses were: 1) data needs for priorities (patient care, mandatory reporting); 2) challenges around infection control, limited equipment, and staff clinical/language proficiencies; 3) patient/clinical flows; and 4) weak points from staff turnover, infection control, and changing protocols. Key outputs included: 1) determining essential data, 2) data tool design decisions (e.g. large font sizes, checkboxes/buttons), 3) data communication methods (e.g. radio, “collective memory”), 4) error reduction methods (e.g. check digits, pre-written wristbands), and 5) data storage options (e.g. encrypted files, accessible folders). Implementation involved building data collection tools (e.g. 13 forms), preparing the systems (e.g. supplies), training staff, and maintenance (e.g. removing old forms). Most patients had basic (100%, n = 456/456), drug (96.9%, n = 442/456), and additional clinical/epidemiological (98.9%, n = 451/456) data stored. The questionnaire responses highlighted the importance of usability and simplicity in the HIS. Conclusions HISs during emergencies are often ad-hoc and disjointed, but systematic design and implementation can lead to high-quality systems focused on efficiency and ease of use. Many of the processes used and lessons learned from our work are generalizable to other health emergencies. Improvements should be started now to have rapidly adaptable and deployable HISs ready for the next health emergency. Electronic supplementary material The online version of this article (10.1186/s12911-019-0817-9) contains supplementary material, which is available to authorized users.

PURPOSE OF REVIEW: Central nervous system (CNS) infections present an ongoing diagnostic challenge for clinicians, with an aetiological agent remaining unidentified in the majority of cases even in high-income settings. This review summarizes developments in a range of diagnostic methods published in the past 18 months. RECENT FINDINGS: Several commercial assays exist for the detection of viral, bacterial and fungal pathogens using single multiplex PCR. Multicentre validation of the Biofire FilmArray panel illustrated high sensitivity for bacterial and fungal pathogens, but poor results for Cryptococcus species detection. The development of microarray cards for bacterial CNS pathogens shows promise but requires further validation. Few developments have been made in proteomics and transcriptomics, contrasted with significant increase in the use of metagenomic (or unbiased) sequencing. Novel viruses causing CNS infection have been described using this technique but contamination, cost, expertise and turnaround time requirements remain restrictive. Finally, the development of Gene Xpert and Ultra has revolutionized tuberculosis meningitis diagnostics with newly released recommendations for their use from the WHO. SUMMARY: Progress has been made in the clinical validation and international recommendation of PCR-based tests for CNS infections. Sequencing techniques present the most dynamic field, although significant ongoing challenges persist.

The frequency of reported outbreaks of infectious diseases has increased over the past 3 decades, with predictions that this rise will continue. Outbreak response continues to follow nine basic principles: establish the presence of an outbreak, verify the diagnosis, make a case definition, find cases and contacts, conduct basic epidemiology, test hypotheses, institute control measures, communicate the situation and establish ongoing surveillance. Within each of these areas, significant advances have been made over the past 5 years using progress in digital, laboratory, epidemiology and anthropological equipment or techniques. Irrespective of these, future outbreaks of high-consequence are inevitable, and vigilance and preparation must continue in order to prevent significant mortality, morbidity and socio-economic crisis.

Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease.We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre.150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (20 cycles), and severe hepatitis were independently associated with mortality.Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates.None.

The unprecedented scale of the 2013-2016 West African Ebola virus disease (EVD) outbreak was in a large part due to failings in surveillance: contacts of confirmed cases were not systematically identified, monitored and diagnosed early, and new cases appearing in previously unaffected communities were similarly not rapidly identified, diagnosed and isolated. Over the course of this epidemic, traditional surveillance methods were strengthened and novel methods introduced. The wealth of experience gained, and the systems introduced in West Africa, should be used in future EVD outbreaks, as well as for other communicable diseases in the region and beyond.

Zika virus is normally transmitted by mosquitos, but cases of sexual transmission have been reported. We describe a patient with symptomatic Zika virus infection in whom the virus was detected in semen for 92 days. Our findings support recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection.

Background: \ud The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact.\ud \ud Methods: \ud We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies.\ud \ud Findings: \ud The assay had a specificity of 100% (95% CI 98·9–100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8–98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1–20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2–4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level.\ud \ud Interpretation: \ud This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions.\ud \ud Funding: \ud Wellcome Trust ERAES Programme, Save the Children.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

Severe adenovirus infections can occur in both immunocompromised and immunocompetent patients. New serotypes are emerging in the UK, and should be considered in patients who present with respiratory tract symptoms and no other obvious pathogen. The difficulties of diagnosis and treatment of severe adenovirus infection are discussed.

Although sub-Saharan Africa contains approximately 12% of the world’s population, it hosts an estimated 68% of all living HIV-infected people (22.5 million persons) and 30% of annual cases of TB (4.4 million persons). In countries with an extended epidemic of both HIV and TB, both infections commonly affect the same individuals. However, TB care services (WHO’s Directly Observed Therapy Short Course) and HIV care services essentially function as separate vertical programs. In 2004, in an effort to improve the management and control of TB and HIV, WHO produced an Interim Policy on collaborative TB/HIV Activities with a range of measures to improve the integration of TB care into HIV treatment programs (intensified TB case finding, isoniazid preventive therapy and TB infection control in healthcare settings) and the integration of HIV care into TB treatment programs (HIV testing and counseling, HIV prevention, co-trimoxazole preventive therapy, HIV/AIDS care and support, and antiretroviral therapy). In this review, we describe and critically discuss the evidence relating to the implementation of the proposed collaborative activities in sub-Saharan Africa.

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD.

Markus Diener and colleagues (July 12, p 142) might believe that the study protocol and sample size account for the confl icting fi ndings in the PROUD trial (not showing a prophylactic effect of triclosancoated sutures against surgical site infection [SSI]) and for findings from smaller randomised controlled trials that show benefits for use in antibiotic sutures in prevention of SSI. However, the discrepancy might be more because of differences in baseline characteristics of participants. Antimicrobial eff ects of triclosancoated sutures seem to depend on the length of skin incision, extent of wound contamination at operation, and concurrent diseases amenable to infections, such as diabetes. In a single-centre randomised trial, investigators reported triclosancoated sutures to be of slight benefi t because they decreased the rate of SSIs after open colorectal surgery, but did not change infection *Claire Bayntun, Catherine Houlihan, John Edmunds clairebayntun@doctors.org.uk

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.