ABSTRACT
Introduction Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected [≥]48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated. Results A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01; P=0.14) or rapid (0.85, 0.48-1.50; P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Conclusion While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.
Subject(s)
COVID-19ABSTRACT
On 26th November 2021, a novel SARS-CoV-2 variant B.1.1.529 (Omicron variant) was designated as a variant of concern by the World Health Organisation. Using data from the Virology laboratory at the Manchester Medical Microbiology Partnership (MMMP, a partnership between UKHSA and the Manchester Foundation Trust), we have extracted a real-time feed of Omicron samples from hospitals across Greater Manchester, an area of the United Kingdom with a population size of approximately three million individuals. Omicron hospital samples are growing exponentially across Greater Manchester (doubling time 2.7 days (95% CI: 2.1, 3.7)). The proportion of Omicron in hospital samples follows a similar trajectory to the SGTF proportion in cases, but with a two-day offset. This is consistent with the delay from testing positive to hospital admission, implying a similar proportion of Omicron cases are converting to hospital admissions as for Delta cases. Comparing the Greater Manchester data to national hospitalisation data, similar tends are observed. Therefore, there is no signal of a substantial reduction in hospital admission risk with Omicron, and Omicron epidemics are likely to place a substantial burden on public health infrastructure.
ABSTRACT
Previous studies have described RT-LAMP methodology for the rapid detection of SARS-CoV-2 in nasopharyngeal/oropharyngeal swab and saliva samples. Here we describe the validation of an improved simple sample preparation method for Direct SARS-CoV-2 RT-LAMP, removing the need for RNA extraction, using 559 swabs and 86,760 saliva samples from asymptomatic and symptomatic individuals across multiple healthcare settings. Using this improved method we report a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT-qPCR ORF1ab CT values of <25 and <33 (high and medium-high viral loads, respectively), we found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) and 87.32% (80.71-92.31%) for saliva. We also describe RNA RT-LAMP (on extracted RNA) performed on 12,619 swabs and 12,521 saliva samples to provide updated performance data with DSe and DSp of 95.98% (92.74-98.06%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. We also report on daily samples collected from one individual from symptom onset where both Direct and RNA RT-LAMP detected SARS-CoV-2 in saliva collected on all six days where symptoms were recorded, with RNA RT-LAMP detecting SARS-CoV-2 for an additional further day. The findings from these studies demonstrate that RT-LAMP testing of swabs and saliva is potentially applicable to a variety of use-cases, including frequent, interval-based testing of saliva from asymptomatic individuals via Direct RT-LAMP that may be missed using symptomatic testing alone.
ABSTRACT
Background: Understanding the effectiveness of infection control methods in reducing and preventing SARS-CoV-2 transmission in healthcare settings is of high importance. Infection control is challenging in these environments due to regular contact between healthcare workers (HCWs) and patients. This is amplified by increased frequency of severe adverse responses to SARS-CoV-2 in patients with underlying health conditions. Methods: We sequenced SARS-CoV-2 genomes for patients and HCWs across multiple geographically distinct UK hospitals. All hospitals were actively enforcing zoning approaches (SARS-CoV-2 negative and SARS-CoV-2 positive areas) as an infection control measure. We integrated patient movement and staff location data into the analysis of viral genome data in order to understand geographical and temporal dynamics of SARS-CoV-2 transmission. Findings: We obtained 173 high-quality SARS-CoV-2 genomes from patients ( n =134) and HCWs ( n =39). The median number of genomic variants per sample of 11 (range=0-16), with a 61.5% average pairwise similarity in the variants (range=0-100%). Integration of patient movement identified eight patient contact clusters (PCC) with significantly increased similarity in genomic variants compared to non-clustered samples ( p <0.001). Incorporation of HCW location further increased the number of individuals within PCCs. Patients within PCCs carried viruses more genetically identical to HCWs in the same ward location ( p <0.001). Interpretation: SARS-CoV-2 genome sequencing integrated with patient and HCW movement data increases identification of outbreak clusters and improved understanding of the role of patient-HCW interactions. This dynamic approach to SARS-CoV-2 outbreak monitoring in a healthcare setting is able to support infection control management strategies within the healthcare setting. Funding: JME is funded by a postdoctoral research fellowship from Health Education England. WGN is supported by the Manchester NIHR BRC (IS-BRC-1215-20007).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was conducted to investigate hospital outbreak investigation/surveillance. Ethical approval was obtained from the Manchester Biomedical Research Centre COVID-19 rapid response group for viral genome analysis.
Subject(s)
Cross Infection , COVID-19ABSTRACT
BackgroundDried blood spot samples (DBS) provide an alternative sample type to venous blood samples for antibody testing. DBS are used by NHS for diagnosing HCV and by PHE for large scale HIV and Hepatitis C serosurveillance; the applicability of DBS based approaches to SARS-CoV-2 antibody detection is uncertain. ObjectiveTo compare antibody detection in dried blood spot eluates using the Roche Elecsys (R) immunoassay (index test) with antibody detection in paired plasma samples, using the same assay (reference test). SettingOne Police and one Fire & Rescue facility in England. Participants195 participants within a larger sample COVID-19 serodiagnostics study of keyworkers, EDSAB-HOME. Outcome MeasuresSensitivity and specificity of DBS (the index test) relative to plasma (the reference test), at an experimental cut-off; quality of DBS sample collected; estimates of relative sensitivity of DBS vs. plasma immunoassay in a larger population. Results18/195 (9.2%) participants tested positive using plasma samples. DBS sample quality varied markedly by phlebotomist, and low sample volume significantly reduced immunoassay signals. Using a cut-off of ten median absolute deviations above the immunoassay result with negative samples, sensitivity and specificity of DBS were 89.0% (95% CI 67.2, 96.9%) and 100.0% (95% CI 97.9, 100%) respectively compared with using plasma. The limit of detection for DBS is about 30 times higher than for plasma. ConclusionDBS use for SARS-CoV-2 serology, though feasible, is insensitive relative to immunoassays on plasma. Sample quality impacts on assay performance. Alternatives, including the collection of capillary blood samples, should be considered for screening programs.
Subject(s)
COVID-19ABSTRACT
IntroductionThe risks to surgeons of carrying out aerosol generating procedures during the COVID pandemic are unknown. To start to define these risks, in a systematic manner, we investigated the presence of SARS-CoV-2 virus in the abdominal fluid and lower genital tract of patients undergoing surgery. MethodsWe carried out a prospective cross sectional observational study of 113 patients undergoing abdominal surgery or instrumentation of the lower genital tract. We took COVID swabs from the peritoneal cavity and from the vagina from all eligible patients. Results were stratified by pre operative COVID status. ResultsIn patients who were presumed COVID negative at the time of surgery SARS-CoV-2 virus RNA was detected in 0/102 peritoneal samples and 0/98 vaginal samples. Peritoneal and vaginal swabs were also negative in one patient who had a positive nasopharyngeal swab immediately prior to surgery. ConclusionsThe presence of SARS-CoV-2 RNA in the abdominal fluid or lower genital tract of presumed negative patients is nil or extremely low. These data will inform surgeons of the risks of restarting laparoscopic surgery at a time when COVID19 is endemic in the population.