Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually ...requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing.
Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing.
We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86–98) with an overall specificity of 100% (99–100). The sensitivity of the test varied by group (self-referred healthcare workers 94% 95% CI 85–98; patients in the emergency department 100% 48–100; and hospital inpatient admissions 100% 29–100). Specificity was consistent between groups (self-referred health-care workers 100% 95% CI 98–100; patients in the emergency department 100% 69–100; and hospital inpatient admissions 100% 96–100). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% 95% 20–31 in April, 2020) and low prevalence (3% 95% 1–9 in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA.
The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes.
National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.
Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism ...in patients who died of severe COVID-19.
In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.
The median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight 89% of nine patients), heart (five 56%), and kidney (four 44%). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two 22% of nine patients), adrenal micro-infarction (three 33%), pericarditis (two 22%), disseminated mucormycosis (one 10% of ten patients), aortic dissection (one 11% of nine patients), and marantic endocarditis (one 11%). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients.
Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19.
Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.
Summary Background An estimated 150 million people worldwide are infected with hepatitis C virus (HCV). HIV co-infection accelerates the progression of HCV and represents a major public health ...challenge. We aimed to determine the epidemiology of HCV and the prevalence of HIV co-infection in sub-Saharan Africa. Methods We searched Medline and Embase (Ovid) from Jan 1, 2002, to Dec 31, 2014, for studies containing data for HCV seroprevalence in different population groups in WHO-defined regions of sub-Saharan Africa. We estimated pooled regional prevalence estimates with a DerSimonian-Laird random-effects model. Data were further stratified by risk factor and HIV status. Findings We included 213 studies from 33 countries in sub-Saharan Africa, comprising 287 separate cohorts with 1 198 167 individuals. The pooled HCV seroprevalence from all cohorts was 2·98% (95% CI 2·86–3·10). The pooled HCV seroprevalence was 2·65% (95% CI 2·53–2·78) across all 185 low-risk cohorts, 3·04% (2·23–3·84) in antenatal clinic groups, 1·99% (1·86–2·12) in blood donors, but 6·9% (6·1–7·5) in other general population cohorts. The pooled seroprevalence of HCV was 11·87% (95% CI 7·05–16·70) across all high-risk groups and 9·95% (6·79–13·11) in patients with liver disease. 101 cohorts included HIV-positive samples tested for HCV (42 648 individuals), with a pooled seroprevalence of 5·73% (95% CI 4·90–6·56). Interpretation We recorded a high seroprevalence of HCV across populations of sub-Saharan Africa, including in HIV-positive adults, with evidence of regional variation in the general population. Monitoring of antenatal HCV prevalence might be a helpful indicator of population trends in HCV infection; however, larger population surveys are needed to monitor these trends. Access to prevention and treatment needs to be improved for both monoinfected and co-infected individuals. Funding None.
Summary Background With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention ...strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. Methods We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). Findings Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval UI 0·86–0·94) to 1·45 million (1·38–1·54); YLLs from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs from 31·7 million (30·2–33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. Interpretation Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. Funding Bill & Melinda Gates Foundation.
Technologies for global health Howitt, Peter, MA; Darzi, Ara, Prof; Yang, Guang-Zhong, Prof ...
The Lancet (British edition),
08/2012, Volume:
380, Issue:
9840
Journal Article
Peer reviewed
Mechanical ventilation and intravenous sedation were initiated. Because of continuing spasms, intrathecal baclofen (1200 µg per day) was started on day 3 with a good clinical response. No ...recommendations about tetanus prophylaxis procedures for wound man agement in patients with blood diseases are available, except for bone-marrow transplantation.
Voluntary licences are increasingly being used to expand access to patented essential medicines in low-income and middle-income countries (LMICs). Since 2014, non-exclusive voluntary licences have ...been issued by Gilead and Bristol-Myers Squibb for key drugs for hepatitis C virus (HCV) infection. We aimed to evaluate the effect of these licences on access to HCV treatment.
We conducted a difference-in-differences analysis, exploiting the staggered and selective introduction of voluntary licensing in different countries, to identify the effect of voluntary licensing agreements on treatment uptake. We extracted Polaris Observatory data on the total number of people infected with HCV, diagnosed with HCV, and treated for HCV, and constructed a longitudinal panel of LMICs over a 13-year period (2004–16). Countries were included if they were classified as LMICs by the World Bank in 2014, and had available data on HCV outcomes. The exposure was defined as inclusion in any voluntary licence agreement for HCV drugs. Treatment uptake was calculated as the number of people treated for HCV in a given year per 1000 living people ever diagnosed with HCV. We fit difference-in-differences linear regression models controlling for different confounders that could influence treatment access and uptake, including country and year fixed effects and a range of country-level factors. We additionally assessed the dynamics of the effect and the robustness of our findings.
35 countries were included in the panel: 19 in the intervention group and 16 in the control group. In the simplest model, adjusting only for country and year fixed effects, voluntary licences were associated with an increase in the annual number of people accessing HCV treatment of 69·3 per 1000 diagnosed (95% CI 46·7–91·9; p=0·0060). After adjusting for country-level covariates, this increase was 53·6 per 1000 diagnosed (25·8–81·5; p=0·0354). The effect of licensing increased over time, and was largest in the second year after implementation. Results were robust to alternative specifications.
Voluntary licensing initiatives appear to substantially improve HCV treatment uptake in eligible countries. This evidence supports the expansion of licensing strategies to include more countries and more treatments.
Unitaid and Médecins Sans Frontières.
Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic ...setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department.
Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities.
A three-gene transcript signature, comprising HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0·976 (95% CI 0·919−1·000), sensitivity of 97·3% (85·8−99·9), and specificity of 100% (63·1−100). The AUROC for C-reactive protein (CRP) was 0·833 (0·694−0·944) and for leukocyte count was 0·938 (0·840−0·986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0·953 (0·893−0·992), sensitivity 88·6%, and specificity of 94·1%.
This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection.
National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7.
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