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Preprint in English | medRxiv | ID: ppmedrxiv-20220699


BackgroundThe 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. MethodsWe 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. Findings410/5,698 (7{middle dot}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{middle dot}47% versus 6{middle dot}16%) Healthcare assistants (aOR 2{middle dot}06 [95%CI 1{middle dot}14-3{middle dot}71]; p=0{middle dot}016) and domestic and portering staff (aOR 3{middle dot}45 [95% CI 1{middle dot}07-11{middle dot}42]; p=0{middle dot}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{middle dot}07 [95% CI 1{middle dot}31-3{middle dot}25]; p<0{middle dot}002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1{middle dot}65 (95% CI 1{middle dot}32 - 2{middle dot}07; p<0{middle dot}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. InterpretationRisk 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. FundingWellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre. Research in context Evidence before this studySpecific risk factors for SARS-CoV-2 infection in healthcare workers (HCWs) are not well defined. Additionally, it is not clear how population level risk factors influence occupational risk in defined demographic groups. Only by identifying these factors can we mitigate and reduce the risk of occupational SARS-CoV-2 infection. We performed a review of the evidence for HCW-specific risk factors for SARS-CoV-2 infection. We searched PubMed with the terms "SARS-CoV-2" OR "COVID-19" AND "Healthcare worker" OR "Healthcare Personnel" AND "Risk factor" to identify any studies published in any language between December 2019 and September 2020. The search identified 266 studies and included a meta-analysis and two observational studies assessing HCW cohort seroprevalence data. Seroprevalence and risk factors for HCW infections varied between studies, with contradictory findings. In the two serological studies, one identified a significant increased risk of seroprevalence in those working with COVID-19 patients (Eyre et al 2020), as well as associations with job role and department. The other study (Dimcheff et al 2020) found no significant association between seropositivity and any identified demographic or occupational factor. A meta-analysis of HCW (Gomez-Ochoa et al 2020) assessed >230,000 participants as a pooled analysis, including diagnoses by both RT-PCR and seropositivity for SARS-CoV-2 antibodies and found great heterogeneity in study design and reported contradictory findings. Of note, they report a seropositivity rate of 7% across all studies reporting SARS-CoV-2 antibodies in HCWs. Nurses were the most frequently affected healthcare personnel and staff working in non-emergency inpatient settings were the most frequently affected group. Our search found no prospective studies systematically evaluating HCW specific risk factors based entirely on seroprevalence data. Added value of this studyOur prospective cohort study of almost 6,000 HCWs at a large UK teaching hospital strengthens previous findings from UK-based cohorts in identifying an increased risk of SARS-CoV-2 exposure amongst HCWs. Specifically, factors associated with SARS-CoV-2 exposure include caring for confirmed COVID-19 cases and identifying as being within specific ethnic groups (BAME staff). We further delineated the risk amongst BAME staff and demonstrate that occupational factors alone do not account for all of the increased risk amongst this group. We demonstrate for the first time that healthcare assistants represent a key at-risk occupational group, and challenge previous findings of significantly higher risk amongst nursing staff. Seroprevalence in staff not working in areas with confirmed COVID-19 patients was only marginally higher than that of the general population within the same geographical region. This observation could suggest the increased risk amongst HCWs arises through occupational exposure to confirmed cases and could account for the overall higher seroprevalence in HCWs, rather than purely the presence of staff in healthcare facilities. Over 30% of seropositive staff had not reported symptoms consistent with COVID-19, and in those who did report symptoms, differentiating COVID-19 from other causes based on symptom data alone was unreliable. Implications of all the available evidenceInternational efforts to reduce the risk of SARS-CoV-2 infection amongst HCWs need to be prioritised. The risk of SARS-CoV-2 infection amongst HCWs is heterogenous but also follows demonstrable patterns. Potential mechanisms to reduce the risk for staff working in areas with confirmed COVID-19 patients include improved training in hand hygiene and personal protective equipment (PPE), better access to high quality PPE, and frequent asymptomatic testing. Wider asymptomatic testing in healthcare facilities has the potential to reduce spread of SARS-CoV-2 within hospitals, thereby reducing patient and staff risk and limiting spread between hospitals and into the wider community. The increased risk of COVID-19 amongst BAME staff cannot be explained by purely occupational factors; however, the increased risk amongst minority ethnic groups identified here was stark and necessitates further evaluation.

Preprint in English | medRxiv | ID: ppmedrxiv-20219642


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.

Preprint in English | medRxiv | ID: ppmedrxiv-20182279


COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1,167 residents from 337 care homes were identified from a dataset of 6,600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population. Impact statementSARS-CoV-2 can spread efficiently within care homes causing COVID-19 outbreaks among residents, who are at increased risk of severe disease, emphasising the importance of stringent infection control in this population.

Preprint in English | medRxiv | ID: ppmedrxiv-20114520


BackgroundThere is urgent need for safe and efficient triage protocols for hospitalized COVID-19 suspects to appropriate isolation wards. A major barrier to timely discharge of patients from the emergency room and hospital is the turnaround time for many SARS-CoV-2 nucleic acid tests. We validated a point of care nucleic acid amplification based platform SAMBA II for diagnosis of COVID-19 and performed an implementation study to assess its impact on patient disposition at a major academic hospital. MethodsWe prospectively recruited COVID-19 suspects admitted to hospital (NCT04326387). In an initial pilot phase, individuals were tested using a nasal/throat swab with the SAMBA II SARS-CoV-2 rapid diagnostic platform in parallel with a combined nasal/throat swab for standard central laboratory RT-PCR testing. In the second implementation phase, we examined the utility of adding the SAMBA platform to routine care. In the pilot phase, we measured concordance and assay validity using the central laboratory as the reference standard and assessed assay turnaround time. In the implementation phase, we assessed 1) time to definitive bed placement from admission, 2) time spent on COVID-19 holding wards, 3) proportion of patients in isolation versus COVID negative areas following a test, comparing the implementation phase with the 10 days prior to implementation. ResultsIn phase I, 149 participants were included in the pilot. By central laboratory RT-PCR testing, 32 (21.5%) tested positive and 117 (78.5%). Sensitivity and specificity of the SAMBA assay compared to RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999), respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II SARS-CoV-2 test and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA implementation phase, we conducted 992 tests, with the majority (59.8%) used for hospital admission, and the remainder for pre-operative screening (11.3%), discharge planning (10%), in-hospital screening of new symptoms (9.7%). Comparing the pre-implementation (n=599) with the implementation phase, median time to definitive bed placement from admission was reduced from 23.4 hours (8.6-41.9) to 17.1 hours (9.0-28.8), P=0.02 in Cox analysis, adjusted for age, sex, comorbidities and clinical severity at presentation. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (P<0.001). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% (P=0.03) and 11 hospital bay closures (on average 6 beds each) were avoided after implementation of the POC assay. ConclusionsThe SAMBA II SARS-CoV-2 rapid assay performed well compared to a centralized laboratory RT-PCR platform and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to definitive bed placement from the emergency room, greater availability of isolation rooms, avoidance of hospital bay closures, and greater movement of patients to COVID negative open "green" category wards. Rapid testing in hospitals has the potential to transform ability to deal with the COVID-19 epidemic.

Preprint in English | medRxiv | ID: ppmedrxiv-20095687


BackgroundThe burden and impact of healthcare-associated COVID-19 infections is unknown. We aimed to examine the utility of rapid sequencing of SARS-CoV-2 combined with detailed epidemiological analysis to investigate healthcare-associated COVID-19 infections and to inform infection control measures. MethodsWe set up rapid viral sequencing of SARS-CoV-2 from PCR-positive diagnostic samples using nanopore sequencing, enabling sample-to-sequence in less than 24 hours. We established a rapid review and reporting system with integration of genomic and epidemiological data to investigate suspected cases of healthcare-associated COVID-19. ResultsBetween 13 March and 24 April 2020 we collected clinical data and samples from 5191 COVID-19 patients in the East of England. We sequenced 1000 samples, producing 747 complete viral genomes. We conducted combined epidemiological and genomic analysis of 299 patients at our hospital and identified 26 genomic clusters involving 114 patients. 66 cases (57.9%) had a strong epidemiological link and 15 cases (13.2%) had a plausible epidemiological link. These results were fed back to clinical, infection control and hospital management teams, resulting in infection control interventions and informing patient safety reporting. ConclusionsWe established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and demonstrated the benefit of combined genomic and epidemiological analysis for the investigation of healthcare-associated COVID-19 infections. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection control interventions to reduce further healthcare-associated infections.