Aerosol formation during processing of potentially infectious samples on Roche immunochemistry analyzers (cobas e analyzers) and in an end-to-end laboratory workflow to model SARS-CoV-2 infection risk for laboratory operators.

Objectives: To assess aerosol formation during processing of model samples in a simulated real-world laboratory setting, then apply these findings to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess the risk of infection to laboratory operators. Design: This study assessed aerosol formation when using cobas e analyzers only and in an end-to-end laboratory workflow. Recombinant hepatitis B surface antigen (HBsAg) was used as a surrogate marker for infectious SARS-CoV-2 viral particles. Using the HBsAg model, air sampling was performed at different positions around the cobas e analyzers and in four scenarios reflecting critical handling and/or transport locations in an end-to-end laboratory workflow. Aerosol formation of HBsAg was quantified using the Elecsys® HBsAg II quant II immunoassay. The model was then applied to SARS-CoV-2. Results: Following application to SARS-CoV-2, mean HBsAg uptake/hour was 1.9 viral particles across the cobas e analyzers and 0.87 viral particles across all tested scenarios in an end-to-end laboratory workflow, corresponding to a maximum inhalation rate of <16 viral particles during an 8-hour shift. Conclusion: Low production of marker-containing aerosol when using cobas e analyzers and in an end-to-end laboratory workflow is consistent with a remote risk of laboratory-acquired SARS-CoV-2 infection for laboratory operators.

Antisense Peptide Technology for Diagnostic Tests and Bioengineering Research.

Antisense peptide technology (APT) is based on a useful heuristic algorithm for rational peptide design. It was deduced from empirical observations that peptides consisting of complementary (sense and antisense) amino acids interact with higher probability and affinity than the randomly selected ones. This phenomenon is closely related to the structure of the standard genetic code table, and at the same time, is unrelated to the direction of its codon sequence translation. The concept of complementary peptide interaction is discussed, and its possible applications to diagnostic tests and bioengineering research are summarized. Problems and difficulties that may arise using APT are discussed, and possible solutions are proposed. The methodology was tested on the example of SARS-CoV-2. It is shown that the CABS-dock server accurately predicts the binding of antisense peptides to the SARS-CoV-2 receptor binding domain without requiring predefinition of the binding site. It is concluded that the benefits of APT outweigh the costs of random peptide screening and could lead to considerable savings in time and resources, especially if combined with other computational and immunochemical methods.

Predicting endoscopic activity recovery in England after COVID-19: a national analysis.

BACKGROUND: The COVID-19 pandemic has led to a substantial reduction in gastrointestinal endoscopies, creating a backlog of procedures. We aimed to quantify this backlog nationally for England and assess how various interventions might mitigate the backlog. METHODS: We did a national analysis of data for colonoscopies, flexible sigmoidoscopies, and gastroscopies from National Health Service (NHS) trusts in NHS England's Monthly Diagnostic Waiting Times and Activity dataset. Trusts were excluded if monthly data were incomplete. To estimate the potential backlog, we used linear logistic regression to project the cumulative deficit between actual procedures performed and expected procedures, based on historical pre-pandemic trends. We then made further estimations of the change to the backlog under three scenarios: recovery to a set level of capacity, ranging from 90% to 130%; further disruption to activity (eg, second pandemic wave); or introduction of faecal immunochemical testing (FIT) triaging. FINDINGS: We included data from Jan 1, 2018, to Oct 31, 2020, from 125 NHS trusts. 10 476 endoscopy procedures were done in April, 2020, representing 9·5% of those done in April, 2019 (n=110 584), before recovering to 105 716 by October, 2020 (84·5% of those done in October, 2019 [n=125 072]). Recovering to 100% capacity on the current trajectory would lead to a projected backlog of 162 735 (95% CI 143 775-181 695) colonoscopies, 119 025 (107 398-130 651) flexible sigmoidoscopies, and 194 087 (172 564-215 611) gastroscopies in January, 2021, attributable to the pandemic. Increasing capacity to 130% would still take up to June, 2022, to eliminate the backlog. A further 2-month interruption would add an extra 15·4%, a 4-month interruption would add an extra 43·8%, and a 6-month interruption would add an extra 82·5% to the potential backlog. FIT triaging of cases that are found to have greater than 10 µg haemoglobin per g would reduce colonoscopy referrals to around 75% of usual levels, with the backlog cleared in early 2022. INTERPRETATION: Our work highlights the impact of the pandemic on endoscopy services nationally. Even with mitigation measures, it could take much longer than a year to eliminate the pandemic-related backlog. Urgent action is required by key stakeholders (ie, individual NHS trusts, Clinical Commissioning Groups, British Society of Gastroenterology, and NHS England) to tackle the backlog and prevent delays to patient management. FUNDING: Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) at University College London, National Institute for Health Research University College London Hospitals Biomedical Research Centre, and DATA-CAN, Health Data Research UK.

Nanobiosensors as new diagnostic tools for SARS, MERS and COVID-19: from past to perspectives.

The severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and novel coronavirus 19 (COVID-19) epidemics represent the biggest global health threats in the last two decades. These infections manifest as bronchitis, pneumonia or severe, sometimes fatal, respiratory illness. The novel coronavirus seems to be associated with milder infections but it has spread globally more rapidly becoming a pandemic. This review summarises the state of the art of nanotechnology-based affinity biosensors for SARS, MERS and COVID-19 detection. The nanobiosensors are antibody- or DNA-based biosensors with electrochemical, optical or FET-based transduction. Various kinds of nanomaterials, such as metal nanoparticles, nanowires and graphene, have been merged to the affinity biosensors to enhance their analytical performances. The advantages of the use of the nanomaterials are highlighted, and the results compared with those obtained using non-nanostructured biosensors. A critical comparison with conventional methods, such as RT-PCR and ELISA, is also reported. It is hoped that this review will provide interesting information for the future development of new reliable nano-based platforms for point-of-care diagnostic devices for COVID-19 prevention and control.

Nanotheranostics against COVID-19: From multivalent to immune-targeted materials.

Destructive impacts of COVID-19 pandemic worldwide necessitates taking more appropriate measures for mitigating virus spread and development of the effective theranostic agents. In general, high heterogeneity of viruses is a major challenging issue towards the development of effective antiviral agents. Regarding the coronavirus, its high mutation rates can negatively affect virus detection process or the efficiency of drugs and vaccines in development or induce drug resistance. Bioengineered nanomaterials with suitable physicochemical characteristics for site-specific therapeutic delivery, highly-sensitive nanobiosensors for detection of very low virus concentration, and real-time protections using the nanorobots can provide roadmaps towards the imminent breakthroughs in theranostics of a variety of diseases including the COVID-19. Besides revolutionizing the classical disinfection procedures, state-of-the-art nanotechnology-based approaches enable providing the analytical tools for accelerated monitoring of coronavirus and associated biomarkers or drug delivery towards the pulmonary system or other affected organs. Multivalent nanomaterials capable of interaction with multivalent pathogens including the viruses could be suitable candidates for viral detection and prevention of further infections. Besides the inactivation or destruction of the virus, functionalized nanoparticles capable of modulating patient's immune response might be of great significance for attenuating the exaggerated inflammatory reactions or development of the effective nanovaccines and medications against the virus pandemics including the COVID-19.

Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.

OBJECTIVE: To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic. DESIGN: We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval. RESULTS: Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%. CONCLUSIONS: Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.

Current and Perspective Diagnostic Techniques for COVID-19.

Since late December 2019, the coronavirus pandemic (COVID-19; previously known as 2019-nCoV) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world. With more than 1,700,000 confirmed cases, the world faces an unprecedented economic, social, and health impact. The early, rapid, sensitive, and accurate diagnosis of viral infection provides rapid responses for public health surveillance, prevention, and control of contagious diffusion. More than 30% of the confirmed cases are asymptomatic, and the high false-negative rate (FNR) of a single assay requires the development of novel diagnostic techniques, combinative approaches, sampling from different locations, and consecutive detection. The recurrence of discharged patients indicates the need for long-term monitoring and tracking. Diagnostic and therapeutic methods are evolving with a deeper understanding of virus pathology and the potential for relapse. In this Review, a comprehensive summary and comparison of different SARS-CoV-2 diagnostic methods are provided for researchers and clinicians to develop appropriate strategies for the timely and effective detection of SARS-CoV-2. The survey of current biosensors and diagnostic devices for viral nucleic acids, proteins, and particles and chest tomography will provide insight into the development of novel perspective techniques for the diagnosis of COVID-19.

Colon capsule endoscopy: an innovative method for detecting colorectal pathology during the COVID-19 pandemic?

AIM: The coronavirus pandemic has led to significant challenges for healthcare delivery across the globe. Non-emergency endoscopic activity in the UK has been postponed, raising concerns of increased delays in the diagnosis of colorectal cancer and a surge in demand once services resume. Measures to mitigate this risk must be considered. METHOD: This paper reviews various investigative modalities for colorectal disease which could be deployed during cessation of colonoscopy services. We focus on colon capsule endoscopy (CCE) due to its relevance during the COVID-19 pandemic and its ability to triage patients effectively to further endoscopic investigations. RESULTS: CT of the abdomen and pelvis has been suggested as a triage tool while access to colonoscopy is limited. However, CT may lead to the spread of COVID-19 as patients attend the hospital, and it exposes them to the risks of radiation. Faecal immunochemistry tests have been demonstrated as a good predictor of colonic pathology and could be safely used to risk stratify patients when prioritizing colonoscopy. CCE is a safe and innovative technology for investigating the colon. Procedures can be carried out in the community and can be conducted safely during the coronavirus pandemic. It has been shown to be an accurate detector of colonic neoplasia and can reduce demand for colonoscopy. CONCLUSION: As colonoscopy services resume, they will probably experience high demand leading to further delays for patients. CCE could be used to reduce the number of patients requiring colonoscopy and triage those requiring further endoscopic investigations appropriately.