Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.

There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway

One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages

The COVID-19 pandemic was officially declared on March 11th, 2020. Since the very beginning, the spread of the virus has been tracked nearly in real-time by worldwide genome sequencing efforts. As of March 2021, more than 830,000 SARS-CoV-2 genomes have been uploaded in GISAID and this wealth of data allowed researchers to study the evolution of SARS-CoV-2 during this first pandemic year. In parallel, nomenclatures systems, often with poor consistency among each other, have been developed to designate emerging viral lineages. Despite general fears that the virus might mutate to become more virulent or transmissible, SARS-CoV-2 genetic diversity has remained relatively low during the first ~ 8 months of sustained human-to-human transmission. At the end of 2020/beginning of 2021, though, some alarming events started to raise concerns of possible changes in the evolutionary trajectory of the virus. Specifically, three new viral variants associated with extensive transmission have been described as variants of concern (VOC). These variants were first reported in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Their designation as VOCs was determined by an increase of local cases and by the high number of amino acid substitutions harboured by these lineages. This latter feature is reminiscent of viral sequences isolated from immunocompromised patients with long-term infection, suggesting a possible causal link. Here we review the events that led to the identification of these lineages, as well as emerging data concerning their possible implications for viral phenotypes, reinfection risk, vaccine efficiency and epidemic potential. Most of the available evidence is, to date, provisional, but still represents a starting point to uncover the potential threat posed by the VOCs. We also stress that genomic surveillance must be strengthened, especially in the wake of the vaccination campaigns

The use of implementation science methods in the design and development of learning resources for students in higher education: An integrative review

This integrative literature review aims to describe and summarise current empirical evidence on the application and outcomes of implementation science theories, models and frameworks in the design and development of educational resources for students in higher education. This may include collation of practical strategies and exemplars as reported in the studies

A survey study investigating perceptions and acceptance of the whole-body imaging techniques used for the diagnosis of myeloma

Introduction: The purpose of this study was to investigate patient perceptions and acceptance of the three whole-body imaging (WBI) modalities used for diagnosing myeloma; radiographic skeletal survey (RSS), low-dose whole-body computed tomography (LD-WBCT) and whole-body magnetic resonanceimaging (WB-MRI). The secondary aim was to explore the factors affecting the acceptance of whole-body imaging for myeloma.Methods: 60 participants (median age ¼ 58.5 years old) recruited from three NHS trusts and social media completed a survey in which they scored their experiences of each WBI modality on nine 5-point rating scales. Spearman's correlation coefficient, KruskaleWallis, ManneWhitney and Wilcoxon signed-ranktests were used to compare scores between different WBI techniques. Participants were invited to provide additional open text responses for interpretation using thematic analysis.Results: All modalities demonstrated high levels of acceptability (median score ¼ 4). WB-MRI was perceived as more stressful (p¼<0.01) and claustrophobic (p¼<0.01) than RSS and LD-WBCT. Thematic analysis showed patients understood the importance of imaging but had concerns about exacerbatedpain and the results. WB-MRI was difficult to tolerate due to its duration. Respondents were averse to the physical manipulation required for RSS while remaining stationary was perceived as a benefit of LDWBCT and WB-MRI. Staff interactions had both positive and negative effects on acceptance.Conclusions: Despite the psychological and physical burdens of WBI, patients accepted its role in facilitating diagnosis. Staff support is vital for facilitating a positive whole-body imaging experience. Healthcare practitioners can improve WBI acceptance by understanding the burdens imposed by WBIand adopting the personalised care model. Implications for practice: Patient experience can be improved by tailoring examinations to individual needs. RSS can be as burdensome as other WBI techniques and could be superseded by LD-WBCT or WBMR

Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

AbstractMonoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.</jats:p

The Quality of Survival (QoS): A concept framework to assist communication and decision making about cancer care.

78 Background: The past decade has seen the development of transitional, novel cancer therapies that lengthen survival, yet data regarding the quality of that survival are limited or unavailable. Improving patient (pt)/healthcare professional (HCP) communication about issues such as QoS might enhance engagement and inform decision-making about future care. For example, the PROACT study (ECC 2015, abs.1715) has shown how little attention is given to family caregiver impact. Our objective is to develop an inclusive framework that will go beyond existing pt-reported outcomes and quality of life (QoL) constructs, and which HCPs may use to communicate with pts. Methods: An electronic database search to investigate the QoS landscape in cancer was conducted and results were articulated into a visual concept map. Subsequently, 20 US pts with metastatic NSCLC were interviewed about their cancer experiences (a similar melanoma pt survey is ongoing) and this input was integrated into the concept map. Areas explored include: symptoms, disease/treatment communication and education, pt expectations about treatment goals and involvement in decision-making, and impacts of all these on pts, families, and friends. Results: In their interviews, pts reported a host of impacts: physical, psychological/emotional, social/relationship, work, and financial. A QoS concept framework was developed to capture the holistic pt experience throughout the continuum of cancer care (during and post treatment) and consisted of 4 interconnected domains: QoL, survival, side effects and economic impact. The severity and persistence of some of the impacts ultimately affect survival, while others affect the ability to preserve or return to normality. Conclusions: While pt experiences are usually discussed and monitored by HCPs, issues identified as most important to pts and families and their variability over time, are rarely assessed formally during survival. These findings support the development of a pt-centric concept map that defines QoS, provides a comprehensive framework for improving communication between pts and their care teams about long-term QoS in cancer, and potentially enables better treatment decisions. </jats:p

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Antibodies are becoming a frontline therapy for SARS-CoV-2, but the risk of viral evolutionary escape remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in Regeneron’s REGN-COV2 cocktail and Eli Lilly’s LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance.</jats:p

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Mapping antibody escape in SARS-CoV-2 Several antibodies are in use or under development as therapies to treat COVID-19. As new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerge, it is important to predict whether they will remain susceptible to antibody treatment. Starr et al. used a yeast library that covers all mutations to the SARS-CoV-2 receptor-binding domain that do not strongly disrupt binding to the host receptor (ACE2) and mapped how these mutations affect binding to three leading anti–SARS-CoV-2 antibodies. The maps identify mutations that escape antibody binding, including a single mutation that escapes both antibodies in the Regeneron antibody cocktail. Many of the mutations that escape single antibodies are circulating in the human population. Science , this issue p. 850 </jats:p