In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein.

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary.

The Extent of Engagement With Telehealth Approaches by Patients With Advanced Cancer: Systematic Review.

BACKGROUND: Telehealth approaches are increasingly being used to support patients with advanced diseases, including cancer. Evidence suggests that telehealth is acceptable to most patients; however, the extent of and factors influencing patient engagement remain unclear. OBJECTIVE: The aim of this review is to characterize the extent of engagement with telehealth interventions in patients with advanced, incurable cancer reported in the international literature. METHODS: This systematic review was registered with PROSPERO (International Prospective Register of Systematic Reviews) and is reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. A comprehensive search of databases was undertaken for telehealth interventions (communication between a patient with advanced cancer and their health professional via telehealth technologies), including MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Sociological Abstracts, and Web of Science, from the inception of each electronic database up until December 31, 2020. A narrative synthesis was conducted to outline the design, population, and context of the studies. A conceptual framework of digital engagement comprising quantitative behavioral measures (frequency, amount, duration, and depth of use) framed the analysis of engagement with telehealth approaches. Frequency data were transformed to a percentage (actual patient engagement as a proportion of intended engagement), and the interventions were characterized by intensity (high, medium, and low intended engagement) and mode of delivery for standardized comparisons across studies. RESULTS: Of the 19,676 identified papers, 40 (0.2%) papers covering 39 different studies were eligible for inclusion, dominated by US studies (22/39, 56%), with most being research studies (26/39, 67%). The most commonly reported measure of engagement was frequency (36/39, 92%), with substantial heterogeneity in the way in which it was measured. A standardized percentage of actual patient engagement was derived from 17 studies (17/39, 44%; n=1255), ranging from 51% to 100% with a weighted average of 75.4% (SD 15.8%). A directly proportional relationship was found between intervention intensity and actual patient engagement. Higher engagement occurred when a tablet, computer, or smartphone app was the mode of delivery. CONCLUSIONS: Understanding engagement for people with advanced cancer can guide the development of telehealth approaches from their design to monitoring as part of routine care. With increasing telehealth use, the development of meaningful and context- and condition-appropriate measures of telehealth engagement is needed to address the current heterogeneity in reporting while improving the understanding of optimal implementation of telehealth for oncology and palliative care. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42018117232; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018117232.