Blood gene expression predicts intensive care unit admission in hospitalised patients with COVID-19.

Background: The COVID-19 pandemic has created pressure on healthcare systems worldwide. Tools that can stratify individuals according to prognosis could allow for more efficient allocation of healthcare resources and thus improved patient outcomes. It is currently unclear if blood gene expression signatures derived from patients at the point of admission to hospital could provide useful prognostic information. Methods: Gene expression of whole blood obtained at the point of admission from a cohort of 78 patients hospitalised with COVID-19 during the first wave was measured by high resolution RNA sequencing. Gene signatures predictive of admission to Intensive Care Unit were identified and tested using machine learning and topological data analysis, TopMD. Results: The best gene expression signature predictive of ICU admission was defined using topological data analysis with an accuracy: 0.72 and ROC AUC: 0.76. The gene signature was primarily based on differentially activated pathways controlling epidermal growth factor receptor (EGFR) presentation, Peroxisome proliferator-activated receptor alpha (PPAR-α) signalling and Transforming growth factor beta (TGF-ß) signalling. Conclusions: Gene expression signatures from blood taken at the point of admission to hospital predicted ICU admission of treatment naïve patients with COVID-19.

Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial.

BACKGROUND: Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use. METHODS: In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy. RESULTS: 200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p < 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p < 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p < 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p < 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p < 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups. CONCLUSIONS: Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

Evaluating the Immune Response in Treatment-Naive Hospitalised Patients With Influenza and COVID-19.

The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body's immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival.

Combined RT-PCR and Host Response Point-of-Care Testing in Patients Hospitalised with Suspected COVID-19: A Prospective Diagnostic Accuracy Study.

INTRODUCTION: RT-PCR has suboptimal sensitivity for the diagnosis of COVID-19. A composite reference standard comprising RT-PCR plus radiological and clinical features has been recommended for diagnostic accuracy studies. The FebriDx finger prick point-of-care test detects an antiviral host response protein (MxA) in 10 min. We evaluated the diagnostic accuracy of FebriDx and RT-PCR compared to a composite reference standard. METHODS: Adults presenting to hospital with suspected COVID-19 were tested by FebriDx and RT-PCR. A composite reference standard was used to classify patients as having COVID-19 based on RT-PCR positivity, or RT-PCR negativity with COVID-19 radiological findings or other clinical criteria. Measures of accuracy were calculated for MxA alone, RT-PCR alone, and both combined. This study is registered with the ISRCTN (ISRCTN14966673) and has completed. RESULTS: A total of 478 patients were tested, with valid results in 475. Of these 475 patients, 222 (46.7%) were classified as having COVID-19; 192 (40.4%) were RT-PCR positive, and 30 (6.3%) were RT-PCR negative and diagnosed on radiological/clinical criteria. Sensitivity of FebriDx MxA vs the composite reference standard was 186/222 (83.8%, 95% CI 78.3-88.4) and was similar to the sensitivity of RT-PCR (192/222 (86.5%, 95% CI 81.3-90.7), (difference of 2.7%, 95% CI - 3.9 to 9.3, p = 0.42). The sensitivity of combined FebriDx and RT-PCR was 208/222 (93.7%) which was superior to both RT-PCR alone (difference of 9.9, 95% CI 4.1-15.9; p = 0.001) and FebriDx MxA alone (difference of 7.2, 95% CI 1.6-12.9; p = 0.011). CONCLUSION: Sensitivity of combined FebriDx and RT-PCR testing was superior to each alone for the detection of COVID-19 in hospital and may improve infection control and treatment decisions.

Validation of the monocyte activation test with three therapeutic monoclonal antibodies.

Pharmaceutical products intended for parenteral use must be free from pyrogenic (fever-inducing) contamination. Pyrogens comprise endotoxins from Gram-negative bacteria and non-endotoxin pyrogens from Gram-positive bacteria, viruses, and fungi. The longstanding compendial test for pyrogens is the rabbit pyrogen test, but in 2010 the monocyte acti-vation test (MAT) for pyrogenic and pro-inflammatory contaminants was introduced into the European Pharmacopoeia (Ph. Eur.) as a non-animal replacement for the rabbit pyrogen test. The present study describes the first product-specific Good Manufacturing Practice validation of Ph. Eur. MAT, Quantitative Test, Method A for the testing of three therapeutic monoclonal antibodies. The study used the MAT version with cryo-preserved peripheral blood mononuclear cells and interleukin-6 as the readout. Much of the data presented here for one of the antibodies was included in a successful product license application to the European Medicines Agency.

Severe COVID-19 pneumonia in an intensive care setting and comparisons with historic severe viral pneumonia due to other viruses.

PURPOSE: Severe viral pneumonia is associated with significant morbidity and mortality. Recent COVID-19 pandemic continues to impose significant health burden worldwide, and individual pandemic waves often lead to a large surge in the intensive care unit (ICU) admissions for respiratory support. Comparisons of severe SARS-CoV-2 pneumonia with other seasonal and nonseasonal severe viral infections are rarely studied in an intensive care setting. METHODS: A retrospective cohort study comparing patients admitted to ICU with COVID-19 between March and June 2020 and those with viral pneumonias between January and December 2019. We compared patient specific demographic variables, duration of illness, ICU organ supportive measures and outcomes between both groups. RESULTS: Analysis of 93 COVID-19 (Group 1) and 52 other viral pneumonia patients (Group 2) showed an increased proportion of obesity (42% vs. 23%, p = 0.02), non-White ethnicities (41% vs. 6%, p < 0.001) and diabetes mellitus (30% vs. 13%, p = 0.03) in Group 1, with lower prevalence of chronic obstructive pulmonary disease (COPD)/asthma (16% vs. 34%, p = 0.02). In Group 1, the neutrophil to lymphocyte ratio was much lower (6.7 vs. 10, p = 0.006), and invasive mechanical ventilation (58% vs. 26%, p < 0.001) was more common. Length of ICU (8 vs. 4, p < 0.001) and hospital stay (22 vs. 11, p < 0.001) was prolonged in Group 1, with no significant difference in mortality. Influenza A and rhinovirus were the most common pathogens in Group 2 (26% each). CONCLUSIONS: Key differences were identified within demographics (obesity, ethnicity, age, ICU scores, comorbidities) and organ support. Despite these variations, there were no significant differences in mortality between both groups. Further studies with larger sample sizes would allow for further assessment of clinical parameters in these patients.

Routine molecular point-of-care testing for SARS-CoV-2 reduces hospital-acquired COVID-19.

OBJECTIVES: Risk of hospital-acquired COVID-19 (HA-COVID-19) infection is increased by cohorting infected and non-infected patients together in assessment areas, whist awaiting laboratory PCR results. Molecular point-of-care tests (mPOCT) reduce time to results and improve patient flow but the impact on HA-COVID-19 is unknown. METHODS: In this pre and post implementation study patients were evaluated across two time periods: March 1st to August 13th 2020, prior to the introduction of mPOCT in medical admissions areas, and 14th August 2020 to 1st April 2021, after mPOCT introduction. The primary outcome was proportion of HA-COVID-19 infection among all COVID-19 positive patients. Secondary outcome measures included time to SARS-CoV-2 results, length of time spent in the medical assessment area and comparison of local, regional and national proportions of HA-COVID-19. RESULTS: 1988 patients were admitted through the acute medicine admission cohorting area and tested for SARS-CoV-2 prior to introducing mPOCT and 4640 afterwards. Median (IQR) time to SARS-CoV-2 result was 6.5 (2.1-17.9) hours prior to introducing mPOCT and 1.0 (0.8-1.3) hours afterwards (p < 0.0001). Median (IQR) duration in the assessment cohort area was 12.0 (4.8-20.6) hours prior to introduction of POCT and 3.2 (2.0-5.6) hours afterwards (p < 0.0001). The proportion of hospital-acquired COVID-19 cases was 108 (16.5%) of 654 prior to introducing mPOCT compared with 168 (9.4%) of 1782 afterwards, (HR 0.55, 95%CI 0.43-0.70; p < 0.0001). In the period following the introduction of mPOCT up to 1st April 2021 the median proportion of HA-COVID-19 was 13.6% (95%CI 8.2-18.9%) locally, compared with 43.8% (95%CI 37.8-49.9%) for all acute NHS trusts regionally and 30.9% (95%CI 28.4-33.5%) for all NHS trusts nationally. CONCLUSIONS: Routine mPOCT for SARS-CoV-2 was associated with reduced time to results, time spent in admission cohort areas, and hospital-acquired COVID-19, compared to laboratory PCR.

FebriDx host response point-of-care testing improves patient triage for coronavirus disease 2019 (COVID-19) in the emergency department.

OBJECTIVES: Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED). DESIGN: We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm. SETTING: Emergency department of a university teaching hospital. PATIENTS: Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a 'high-risk' area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area. RESULTS: Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34-92) for FebriDx-negative patients and 203 minutes (IQR, 142-255) for FebriDx-positive patients (difference of -134 minutes; 95% CI, -144 to -122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%-97%). CONCLUSIONS: FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2-positive patients.

A SARS-CoV-2 nucleocapsid ELISA represents a low-cost alternative to lateral flow testing for community screening in LMI countries.

Background Controlling the spread of SARS-CoV-2 is problematic because of transmission driven by asymptomatic and pre-symptomatic individuals. Community screening can help identify these individuals but is often too expensive for countries with limited health care resources. Low-cost ELISA assays may address this problem, but their use has not yet been widely reported. Methods We developed a SARS-CoV-2 nucleocapsid ELISA and assessed its diagnostic performance on nose and throat swab samples from UK hospitalised patients and sputum samples from patients in Ghana. Results The ELISA had a limit of detection of 8.4 pg/ml antigen and 16 pfu/ml virus. When tested on UK samples (128 positive and 10 negative patients), sensitivity was 58.6% (49.6-67.2) rising to 78.3% (66.7-87.3) if real-time PCR Ct values > 30 were excluded, while specificity was 100% (69.2-100). In a second trial using the Ghanaian samples (121 positive, 96 negative), sensitivity was 52% (42.8-61.2) rising to 72.6% (61.8-81.2) when a > 30 Ct cut-off was applied, while specificity was 100% (96.2-100). Conclusions: Our data show that nucleocapsid ELISAs can test a variety of patient sample types while achieving levels of sensitivity and specificity required for effective community screening. Further investigations into the opportunities that this provides are warranted.

SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death.

Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.

Escherichia coli EC93 deploys two plasmid-encoded class I contact-dependent growth inhibition systems for antagonistic bacterial interactions.

The phenomenon of contact-dependent growth inhibition (CDI) and the genes required for CDI (cdiBAI) were identified and isolated in 2005 from an Escherichia coli isolate (EC93) from rats. Although the cdiBAIEC93 locus has been the focus of extensive research during the past 15 years, little is known about the EC93 isolate from which it originates. Here we sequenced the EC93 genome and find two complete and functional cdiBAI loci (including the previously identified cdi locus), both carried on a large 127 kb plasmid. These cdiBAI systems are differentially expressed in laboratory media, enabling EC93 to outcompete E. coli cells lacking cognate cdiI immunity genes. The two CDI systems deliver distinct effector peptides that each dissipate the membrane potential of target cells, although the two toxins display different toxic potencies. Despite the differential expression and toxic potencies of these CDI systems, both yielded similar competitive advantages against E. coli cells lacking immunity. This can be explained by the fact that the less expressed cdiBAI system (cdiBAIEC93-2) delivers a more potent toxin than the highly expressed cdiBAIEC93-1 system. Moreover, our results indicate that unlike most sequenced CDI+ bacterial isolates, the two cdi loci of E. coli EC93 are located on a plasmid and are expressed in laboratory media.

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. AREAS COVERED: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting. EXPERT OPINION: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.

How are rapid diagnostic tests for infectious diseases used in clinical practice: a global survey by the International Society of Antimicrobial Chemotherapy (ISAC).

Novel rapid diagnostic tests (RDTs) offer huge potential to optimise clinical care and improve patient outcomes. In this study, we aim to assess the current patterns of use around the world, identify issues for successful implementation and suggest best practice advice on how to introduce new tests. An electronic survey was devised by the International Society of Antimicrobial Chemotherapy (ISAC) Rapid Diagnostics and Biomarkers working group focussing on the availability, structure and impact of RDTs around the world. It was circulated to ISAC members in December 2019. Results were collated according to the UN human development index (HDI). 81 responses were gathered from 31 different countries. 84% of institutions reported the availability of any test 24/7. In more developed countries, this was more for respiratory viruses, whereas in high and medium/low developed countries, it was for HIV and viral hepatitis. Only 37% of those carrying out rapid tests measured the impact. There is no 'one-size fits all' solution to RDTs: the requirements must be tailored to the healthcare setting in which they are deployed and there are many factors that should be considered prior to this.

Clinical impact of a routine, molecular, point-of-care, test-and-treat strategy for influenza in adults admitted to hospital (FluPOC): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Diagnosis of influenza in patients admitted to hospital is delayed due to long turnaround times with laboratory testing, leading to inappropriate and late antiviral treatment and isolation facility use. Molecular point-of-care tests (mPOCTs) are highly accurate, easy to use, and generate results in less than 1 h, but high-quality evidence for their effect on management and clinical outcomes is needed. The aim of this study was to assess the clinical impact of an mPOCT on influenza detection, antiviral use, infection control measures, and clinical outcomes in adults admitted to hospital with acute respiratory illness. METHODS: In this multicentre, pragmatic, open-label, randomised controlled trial (FluPOC), we recruited adults admitted to hospital with acute respiratory illness during influenza seasons from two hospitals in Hampshire, UK. Eligible patients were aged 18 years and older, with acute respiratory illness of 10 days or fewer duration before admission to hospital, who were recruited within 16 h of admission to hospital. Participants were randomly assigned (1:1), using random permuted blocks of varying sizes (4, 6 and 8), to receive mPOCT for influenza or routine clinical care (control group). The primary outcome was the proportion of patients infected with influenza who were treated appropriately with antivirals (neuraminidase inhibitors) within 5 days of admission. Safety was assessed in all patients. Secondary outcomes included time to antivirals, isolation facility use, and clinical outcomes. This study is registered with the ISRCTN registry, ISRCTN17197293, and is now complete. FINDINGS: Between Dec 12, 2017, and May 3, 2019, over two influenza seasons, 613 patients were enrolled, of whom 307 were assigned to the mPOCT group and 306 to the control group, and all were analysed. Median age was 62 years (IQR 45-75) and 332 (54%) of 612 participants with data were female. 100 (33%) of 307 patients in the mPOCT group and 102 (33%) of 306 in the control group had influenza. 100 (100%) of 100 patients with influenza were diagnosed in the mPOCT group and 60 (59%) of 102 were diagnosed though routine clinical care in the control group (relative risk 1·7, 95% CI 1·7-1·7; p<0·0001). 99 (99%) of 100 patients with influenza in the mPOCT group were given antiviral treatment within 5 days of admission versus 63 (62%) 102 in the control group (relative risk 1·6, 95% CI 1·4-1·9; p<0·0001). Median time to antivirals was 1·0 h (IQR 0·0 to 2·0) in the mPOCT group versus 6·0 h (0·0 to 12·0) in the control group (difference of 5·0 h [95% CI 0·0-6·0; p=0·0039]). 70 (70%) of 100 patients with influenza in the mPOCT group were isolated to single-room accommodation versus 39 (38%) of 102 in the control group (relative risk 1·8 [95% CI 1·4-2·4; p<0·0001]). 19 adverse events occurred among patients with influenza in the mPOCT group compared with 34 events in the control group. No patients with influenza died in the mPOCT group and two (2%) died in the control group (p=0·16). INTERPRETATION: Routine mPOCT for influenza was associated with improved influenza detection and improvements in appropriate and timely antiviral and isolation facility use. Routine mPOCT should replace laboratory-based diagnostics for acute admissions to hospital during the influenza season. FUNDING: National Institute for Health Research.

SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study.

OBJECTIVES: The effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults. METHODS: Data for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years. RESULTS: 856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001). CONCLUSIONS: The emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.

Host adaptation and microbial competition drive Ralstonia solanacearum phylotype I evolution in the Republic of Korea.

Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) threatens the cultivation of important crops worldwide. We sequenced 30 RSSC phylotype I (R. pseudosolanacearum) strains isolated from pepper (Capsicum annuum) and tomato (Solanum lycopersicum) across the Republic of Korea. These isolates span the diversity of phylotype I, have extensive effector repertoires and are subject to frequent recombination. Recombination hotspots among South Korean phylotype I isolates include multiple predicted contact-dependent inhibition loci, suggesting that microbial competition plays a significant role in Ralstonia evolution. Rapid diversification of secreted effectors presents challenges for the development of disease-resistant plant varieties. We identified potential targets for disease resistance breeding by testing for allele-specific host recognition of T3Es present among South Korean phyloype I isolates. The integration of pathogen population genomics and molecular plant pathology contributes to the development of location-specific disease control and development of plant cultivars with durable resistance to relevant threats.

Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study.

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. METHODS: We 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.