Background The management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals, these delays lead to poor patient flow and nosocomial transmission. Rapid, accurate tests are therefore urgently needed in preparation for the next wave of the pandemic. MethodsWe did a prospective, interventional, non-randomised, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19 to the emergency department or other acute areas of Southampton General Hospital during the first wave of the pandemic in the UK. Nose and throat swab samples taken at admission from patients in the point-of-care testing group were tested with the QIAstat-Dx Respiratory SARS-CoV-2 Panel. Samples taken from patients in a contemporaneous control group were tested by laboratory PCR. The primary outcome was time to results in the full cohort. This study is registered with ISRCTN (ISRCTN14966673) and is completed. Findings Between March 20 and April 29, 2020, 517 patients were assessed for eligibility, of whom 499 were recruited to the point-of-care testing group and tested by the QIAstat-Dx Respiratory SARS-CoV-2 Panel. 555 contemporaneously identified patients were included in the control group and tested by laboratory PCR. The two groups were similar with regard to the distribution of sex, age, and ethnicity. 197 (39%) patients in the point-of-care testing group and 155 (28%) in the control group tested positive for COVID-19 (difference 11•5% [95% CI 5•8-17•2], p=0•0001). Median time to results was 1•7 h (IQR 1•6-1•9) in the point-of-care testing group and 21•3 h (16•0-27•9) in the control group (difference 19•6 h [19•0-20•3], p<0•0001). A Cox proportional hazards regression model controlling for age, sex, time of presentation, and severity of illness also showed that time to results was significantly shorter in the point-of-care testing group than in the control group (hazard ratio 4023 [95% CI 545-29 696], p<0•0001). Interpretation Point-of-care testing is associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralised laboratory PCR testing. Funding University Hospitals Southampton NHS Foundation Trust.
Introduction: Management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and so rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 min, but its accuracy for the identification of COVID-19 is unknown. Methods: We performed a real-world diagnostic accuracy study of FebriDx in hospitalised patients during the first wave of the pandemic. Measures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of SARS-CoV-2 PCR on combined nose and throat swabs. A multivariable predictive model including FebriDx, age, sex, and clinical characteristics was developed and underwent internal validation. Results: FebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. FebriDx results were available after 10 min compared with 1.7 (1.6 to 2.1) hours with point-of-care PCR testing and 23.4 (17.2 to 31.1) hours with laboratory PCR testing. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model age, sex and other clinical features did not contribute significantly to the effect of the FebriDx result in distinguishing patients with and without COVID-19. Conclusions: During the first wave of the pandemic, FebriDx had high accuracy for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool.
Ventenata [Ventenata dubia (Leers) Coss.], an invasive winter annual grass, significantly reduces forage production in grassland systems and displaces species within both perennial- and annual-dominated grasslands within the Inland Northwest. The range of V. dubia is expanding into sagebrush steppe communities, an expansive habitat critical for forage production, wildlife, and recreation. Currently, there is limited knowledge of V. dubia’s distribution and abundance within sagebrush steppe communities. We performed field surveys at 15 locations in sagebrush steppe rangelands in southern Idaho and eastern Oregon to assess where V. dubia occurs, with the aim of providing insight about its niche in this new habitat. Specifically, we evaluated biotic and abiotic factors of the plant community as indicators of V. dubia presence. We also correlated species diversity measures with no, low (<12.5%), and high (>12.5%) V. dubia cover. Though widely distributed throughout the study region, V. dubia only appeared in 45% of the 225 plots, and foliar cover was typically less than 50%. It was primarily found in ephemerally wet microhabitats. Species richness and the Shannon diversity index were lowest in plots with high V. dubia cover. Nonmetric multidimensional scaling analysis revealed that V. dubia and medusahead [Taeniatherum caput-medusae (L.) Nevski] were closely associated. Furthermore, chi-square indicator analysis showed that T. caput-medusae was more prevalent, while mountain big sagebrush [Artemisia tridentata Nutt. spp. vaseyana (Rydb.) Beetle] was less prevalent, in plots containing V. dubia. Abiotic factors that explained variation in V. dubia abundance included rock cover, soil depth, and a north/south aspect. Higher V. dubia cover also correlated with higher clay content and lower phosphorus and potassium concentrations in the soil. We suggest that at this point, detection survey efforts to locate incipient infestations of V. dubia in sagebrush steppe communities should focus on moist areas and sites susceptible to invasion by T. caput-medusae.
Objectives: Most reports describing the characteristics of patients hospitalised with COVID-19 lack a comparator group. We compared clinical characteristics, symptoms, and outcomes of adults presenting to hospital during the pandemic first wave, who tested positive and negative for SARS-CoV-2. Methods: Detailed patient data was obtained from a large, controlled, non-randomised trial of molecular point-of-care testing versus laboratory RT-PCR for SARS-CoV-2 in adults presenting to a large UK hospital with suspected COVID-19. Results: 1054 patients were included: 352 (33.4%) tested positive and 702 (66.6%) negative. 13.4% (47/352) COVID-19-positive patients had COPD versus 18.7% (131/702) of COVID-19-negative patients (difference = 5.3% [95%CI −9.7% to −0.5%], p = 0.0297). 5.7% (20/352) of COVID-19-positive patients were smokers versus 16.5% (116/702) of negative patients (difference = −10.8% [ −14.4% to −7.0%], p = 0.0 0 01). 70.5% (248/352) of COVID-19-positive patients were White-British versus 85.5% (600/702) of negative patients (difference = −15.0% [ −20.5% to −9.7%], p < 0.0 0 01). 20.9% (39/187) of COVID-19-positive patients were healthcare workers versus 5.2% (15/287) of negative patients (p < 0.0 0 01). Anosmia was reported in 33.1% (47/142) versus 8.8% (19/216) of COVID-19-positive and negative patients respectively (p < 0.0 0 01). Non-SARS-CoV-2 respiratory viruses or atypical bacteria were detected in 2.5% (5/197) of COVID-19 patients versus 7.9% (24/302) of COVID-19-negative patients (p = 0.0109). Hospitalisation duration and 30-day-mortality were higher in COVID-19 patients and invasive ventilation was more frequent (11.1% vs 2.8%, p < 0.0 0 01), and longer (14.5 vs 4.7 days, p = 0.0015). Conclusions: There were substantial differences between patients with and without COVID-19 in terms of ethnicity, healthcare worker-status, comorbidities, symptoms, and outcomes. These data can inform healthcare planning for the next phase of the pandemic.
Transcriptionally silent HIV proviruses form the major obstacle to eradicating HIV. Many studies of HIV latency have focused on the cellular mechanisms that maintain silencing of proviral DNA. Here we show that viral sequence variation affecting replicative ability leads to variable rates of silencing and ability to reactivate. We studied naturally occurring and engineered polymorphisms in a recently identified exonic splice enhancer (ESEtat) that regulates tat mRNA splicing and constructed viruses with increased (strain M1), reduced (strain M2), or completely absent (strain ERK) binding of splicing factors essential for optimal production of tat mRNA resulting in a corresponding change in Tat activity. The mutations affected viral replication, with M1 having wild-type (WT) kinetics, M2 exhibiting reduced kinetics, and ERK showing completely abrogated replication. Using single-round infection with green fluorescent protein (GFP)-expressing viruses to study proviral gene expression, we observed progressively greater rates of silencing relating to the degree of ESEtat disruption, with the WT strain at 53%, strain M2 at 69%, and strain ERK at 94%. By stimulating infected cells with a latency reversal agent (phorbol myristate acetate [PMA], panobinostat, or JQ1), we observed that the dose required to achieve 50% of the maximum signal was lowest in the WT, intermediate in M2, and highest in ERK, indicating progressively higher thresholds for reactivation. These results suggest that the ability of silent proviruses to reactivate from latency is variable and that minor differences in the viral sequence can alter the proportion of silenced viruses as well as the threshold required to induce silenced viruses to reactivate and express. IMPORTANCE A reservoir of infected cells in which the HIV genome is transcriptionally silent is acknowledged to be the principal barrier to eradicating the virus from an infected person. A number of cellular processes are implicated in this silencing; however, the viral factors that may contribute remain underexplored. Here we examined mutations altering the correct splicing of HIV gene products as a model to study whether differences in viral sequence can affect either the proportion of viruses that are active or silent or their ability to reactivate. We found that some naturally occurring variations result in viruses that are silenced at a higher rate and require a proportionally increased stimulus for reactivation from latency. These data suggest that the silencing and reactivation behavior of HIV exists in a spectrum, influenced by factors intrinsic to the virus.
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