Bacteraemia Variation During The COVID-19 Pandemic; A Multi-Centre UK Secondary Care Ecological Analysis. (preprint)

Objectives – We investigated for change in blood stream infections (BSI) with Enterobacterales, coagulase negative staphylococci (CoNS), Streptococcus pneumoniae, and Staphylococcus aureus during the first UK wave of SARS-CoV-2 across six London hospitals.Methods – A retrospective multicentre ecological analysis was undertaken evaluating all blood cultures taken from adults from 01 April 2017 to 30 April 2020 across six acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation.Results –119,584 blood cultures were included. At the height of the UK SARS-CoV-2 first wave in April 2020, Enterobacterales bacteraemias were at an historic low across two London trusts (63/3814, 1.65%), whilst CoNS were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p=0.013) and CoNS (p<0.01), when compared with prior periods, even allowing for seasonal variation. S. pneumoniae (p=0.631) and S. aureus (p=0.617) BSI did not vary significant throughout the study period.Conclusions – Significantly fewer than expected Enterobacteriales BSI occurred during the UK peak of the COVID-19 pandemic; identifying potential causes, including potential unintended consequences of national self-isolation public health messaging, is essential. High rates of CoNS BSI, presumably representing contamination associated with increased use of personal protective equipment, may result in inappropriate antimicrobial use and indicates a clear area for intervention during further waves.

CovidNudge: diagnostic accuracy of a novel lab-free point-of-care diagnostic for SARS-CoV-2 (preprint)

Background Access to rapid diagnosis is key to the control and management of SARS-CoV-2. Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR) testing usually requires a centralised laboratory and significant infrastructure. We describe the development and diagnostic accuracy assessment of a novel, rapid point-of-care RT-PCR test, the DnaNudge platform CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods Nasopharyngeal swabs are 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 a positive control. Between April and May 2020, swab samples were tested in parallel using the CovidNudge direct-to-cartridge platform and standard laboratory RT-PCR using swabs in viral transport medium. Samples were collected from three groups: self-referred healthcare workers with suspected COVID-19 (Group 1, n=280/386; 73%); patients attending the emergency department with suspected COVID-19 (Group 2, n=15/386; 4%) and hospital inpatient admissions with or without suspected COVID-19 (Group 3, n=91/386; 23%). Results Of 386 paired samples tested across all groups, 67 tested positive on the CovidNudge platform and 71 with standard laboratory RT-PCR. The sensitivity of the test varied by group (Group 1 93% [84-98%], Group 2 100% [48-100%] and Group 3 100% [29-100%], giving an average sensitivity of 94.4% (95% confidence interval 86-98%) and an overall specificity of 100% (95%CI 99-100%; Group 1 100% [98-100%]; Group 2 100% [69-100%] and Group 3 100% [96-100%]). Point of care testing performance was comparable during a period of high (25%) and low (3%) background prevalence. Amplification of the viral nucleocapsid (n1, n2, n3) targets were most sensitive for detection of SARS-CoV2, with the assay able to detect 1x104 viral particles in a single swab. Conclusions The CovidNudge platform offers a sensitive, specific and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The implementation of such a device could be used to enable rapid decisions for clinical care and testing programs.

Cardiometabolic traits, sepsis and severe covid-19 with respiratory failure: a Mendelian randomization investigation (preprint)

ObjectivesTo investigate whether there is a causal effect of cardiometabolic traits on risk of sepsis and severe covid-19. DesignMendelian randomisation analysis. SettingUK Biobank and HUNT study population-based cohorts for risk of sepsis, and genome-wide association study summary data for risk of severe covid-19 with respiratory failure. Participants12,455 sepsis cases (519,885 controls) and 1,610 severe covid-19 with respiratory failure cases (2,205 controls). ExposureGenetic variants that proxy body mass index (BMI), lipid traits, systolic blood pressure, lifetime smoking score, and type 2 diabetes liability - derived from studies considering between 188,577 to 898,130 participants. Main outcome measuresRisk of sepsis and severe covid-19 with respiratory failure. ResultsHigher genetically proxied BMI and lifetime smoking score were associated with increased risk of sepsis in both UK Biobank (BMI: odds ratio 1.38 per standard deviation increase, 95% confidence interval [CI] 1.27 to 1.51; smoking: odds ratio 2.81 per standard deviation increase, 95% CI 2.09-3.79) and HUNT (BMI: 1.41, 95% CI 1.18 to 1.69; smoking: 1.93, 95% CI 1.02-3.64). Higher genetically proxied BMI and lifetime smoking score were also associated with increased risk of severe covid-19, although with wider confidence intervals (BMI: 1.75, 95% CI 1.20 to 2.57; smoking: 3.94, 95% CI 1.13 to 13.75). There was limited evidence to support associations of genetically proxied lipid traits, systolic blood pressure or type 2 diabetes liability with risk of sepsis or severe covid-19. Similar findings were generally obtained when using Mendelian randomization methods that are more robust to the inclusion of pleiotropic variants, although the precision of estimates was reduced. ConclusionsOur findings support a causal effect of elevated BMI and smoking on risk of sepsis and severe covid-19. Clinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity, along with the plethora of other health-related outcomes that these traits adversely affect. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LISepsis and severe covid-19 are major contributors to global morbidity and mortality. C_LIO_LICardiometabolic risk factors have been associated with risk of sepsis and severe covid-19, but it is unclear if they are having causal effects. C_LI What this study addsO_LIUsing Mendelian randomization analyses, this study provides evidence to support that higher body mass index and lifetime smoking score both increase risk of sepsis and severe covid-19 with respiratory failure. C_LIO_LIClinical and public health interventions targeting obesity and smoking are likely to reduce sepsis and covid-19 related morbidity, along with the plethora of other health-related outcomes that these traits adversely affect. C_LI