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.

Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes (preprint)

Background: Accurately predicting patient outcomes in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2.MethodBetween March 1 - April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: 1) a Cox regression model and 2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration.Results Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI): 73.8 - 91.1 and 90.0%, 95% CI: 81.2 - 95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI: 91.1 - 94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI: 85.7 - 88.2), p=0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. ConclusionWe demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.

Point-of-care serological assays for SARS-CoV-2 in a UK hospital population: potential for enhanced case finding (preprint)

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility.We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13. Specificity was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.