A Prospective Study of Risk Factors Associated with Seroprevalence of SARS-CoV-2 Antibodies in Healthcare Workers at a Large UK Teaching Hospital (preprint)

Background: The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described.Methods: We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression.Findings: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p =0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p =0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p <0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 – 2·07; p <0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms.Interpretation: Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.Funding: Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.Declaration of Interests: None to declare.Ethics Approval Statement: Ethical approval for this study was granted by the East of England – Cambridge Central Research Ethics Committee (IRAS ID: 220277).

A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital (preprint)

Background The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described. Methods We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. Findings 410/5,698 (7.2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9.47% versus 6.16%) Healthcare assistants (aOR 2.06 [95%CI 1.14-3.71]; p=0.016) and domestic and portering staff (aOR 3.45 [95% CI 1.07-11.42]; p=0.039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2.07 [95% CI 1.31-3.25]; p=0.002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1.65 (95% CI 1.32-2.07; p<0.0001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms. Interpretation Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors. Funding Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.

A2B-COVID: A method for evaluating potential SARS-CoV-2 transmission events (preprint)

Identifying linked cases of infection is a key part of the public health response to viral infectious disease. Viral genome sequence data is of great value in this task, but requires careful analysis, and may need to be complemented by additional types of data. The Covid-19 pandemic has highlighted the urgent need for analytical methods which bring together sources of data to inform epidemiological investigations. We here describe A2B-COVID, an approach for the rapid identification of linked cases of coronavirus infection. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and novel approaches to genome sequence data to assess whether or not cases of infection are consistent or inconsistent with linkage via transmission. We apply our method to analyse and compare data collected from two wards at Cambridge University Hospitals, showing qualitatively different patterns of linkage between cases on designated Covid-19 and non-Covid-19 wards. Our method is suitable for the rapid analysis of data from clinical or other potential outbreak settings.

Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia (preprint)

Background The diagnosis of infectious diseases has been hampered by reliance on microbial culture. Cultures take several days to return a result and organisms frequently fail to grow. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and mitigates against stewardship. Methods Single ICU observational cohort study with contemporaneous comparator group. We developed and implemented a TaqMan array card (TAC) covering 52 respiratory pathogens in ventilated patients undergoing bronchoscopic investigation for suspected pneumonia. The time to result was compared against conventional culture, and sensitivity compared to conventional microbiology and metagenomic sequencing. We observed the clinician decisions in response to array results, comparing antibiotic free days (AFD) between the study cohort and comparator group. Findings 95 patients were enrolled with 71 forming the comparator group. TAC returned results 61 hours (IQR 42-90) faster than culture. The test had an overall sensitivity of 93% (95% CI 88-97%) compared to a combined standard of conventional culture and metagenomic sequencing, with 100% sensitivity for most individual organisms. In 54% of cases the TAC results altered clinical management, with 62% of changes leading to de-escalation, 30% to an increase in spectrum, and investigations for alternative diagnoses in 9%. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). Interpretation Implementation of a customised syndromic diagnostic for pneumonia led to faster results, with high sensitivity and measurable impact on clinical decision making. Funding Addenbrookes Charitable Trust, Wellcome Trust and Cambridge NIHR BRC

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission (preprint)

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B{middle dot}1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

A blueprint for the implementation of a validated approach for the detection of SARS-Cov2 in clinical samples in academic facilities (preprint)

The COVID-19 pandemic is expanding at an unprecedented rate. As a result, diagnostic services are stretched to their limit, and there is a clear need for the provision of additional diagnostic capacity. Academic laboratories, many of which are closed due to governmental lockdowns, may be in a position to support local screening capacity by adapting their current laboratory practices. Here, we describe the process of developing a SARS-Cov2 diagnostic workflow in a conventional academic Containment Level 2 (CL2) laboratory. Our outline includes simple SARS-Cov2 deactivation upon contact, the methods for a quantitative real-time reverse transcriptase PCR (qRT-PCR) detecting SARS-Cov2, a description of process establishment and validation, and some considerations for establishing a similar workflow elsewhere. This was achieved under challenging circumstances through the collaborative efforts of scientists, clinical staff, and diagnostic staff to mitigate to the ongoing crisis. Within 14 days, we created a validated COVID-19 diagnostics service for healthcare workers in our local hospital. The described methods are not exhaustive, but we hope may offer support to other academic groups aiming to set up something comparable in a short time frame.