Comparative analysis of SARS-CoV-2 variants with two high-throughput sequencing platforms

Whole-genome sequencing of upper respiratory tract specimens from patients with confirmed COVID-19 in Henan Province was performed to compare the performance of the Illumina and Oxford Nanopore sequencing platforms, thus providing a reference for whole-genome monitoring of the novel coronavirus (SARS-CoV-2). Ten samples from COVID-19 cases in Henan Province from June 2021 to January 2022 were collected and sequenced with Illumina and Nanopore high-through-put sequencing technology to obtain full genome sequences of the novel coronavirus, which were compared with the Wuhan reference sequence (Wuhan-Hu-1). Bioinformatics software (CLC) was used for sequence alignment analysis. Three of the ten samples were Omicron (BA.1) variants with 55,61 nucleotide variation sites. One sample was an Alpha (B.1.1.7) variant with 41 nucleotide variation sites. Six samples were Delta (8.1.617.2) variants with 35,42,47 nucleotide variation sites. The sequence identity of mutation sites in six samples was 100%, and the mutation sites in the S genome segment of seven samples were consistent. For samples with a Ct value < 33, both next-generation and third-generation sequencing achieved high genome coverage and sequencing depth. A significant difference in coverage was observed between second-generation sequencing and third-generation sequencing (t=-2.037, P < 0.06). However, the coverage at different time points of the third-generation sequencing did not significantly differ (F=2.498, P > 0.05). The needs for SARS-CoV-2 mutant detection could be met through use of either high-throughput sequencing platform. The identification of mutations in the novel coronavirus through Illumina high-throughput sequencing was more accurate, whereas Nanopore high-throughput sequencing technology could be used for rapid detection and typing of different novel coronaviruses.

Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.

An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition.

The main protease from SARS-CoV-2 (Mpro) is responsible for cleavage of the viral polyprotein. Mpro self-processing is called maturation, and it is crucial for enzyme dimerization and activity. Here we use C145S Mpro to study the structure and dynamics of N-terminal cleavage in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed of cleaved and uncleaved particles, indicating that N-terminal processing is not critical for dimerization. A 3.5 Å cryo-EM structure provides details of Mpro N-terminal cleavage outside the constrains of crystal environment. We show that different classes of inhibitors shift the balance between oligomeric states. While non-covalent inhibitor MAT-POS-e194df51-1 prevents dimerization, the covalent inhibitor nirmatrelvir induces the conversion of monomers into dimers, even with intact N-termini. Our data indicates that the Mpro dimerization is triggered by induced fit due to covalent linkage during substrate processing rather than the N-terminal processing.

A Mental Wealth perspective: crossing disciplines to understand the value of collective mental and social assets in the post-COVID-19 era.

BACKGROUND: A reconceptualised global strategy is key as nations begin to shift from crisis management to medium- and long-term planning to rebuild and strengthen their economic, social and public health systems. Efforts towards measuring, modelling, and forecasting Mental Wealth could serve as the catalyst for this reconceptualization. The Mental Wealth approach builds systemic resilience through investments which promote collective cognitive and emotional wellbeing. This paper presents the theoretical foundations for Mental Wealth. It presents, for the first time, literature across the disciplines of health and social sciences, economics, business, and humanities to underpin the development of an operational metric of Mental Wealth. DISCUSSION: An approach which embeds social and psychological dimensions of prosperity, alongside the economic, is needed to inform the effective allocation of investments in the post-pandemic world. The authors advocate for a transdisciplinary framework of Mental Wealth to be applied in innovating population-level policy interventions to address the growing challenges brought on by COVID-19. Mental Wealth highlights the value generated by the deployment of collective mental assets and supporting social infrastructure. In order to inform this position, a review of the literature on the concepts underpinning Mental Wealth is presented, limitations of current measurement tools of mental and social resources are evaluated, and a framework for development of a Mental Wealth metric is proposed. CONCLUSION: There are challenges in developing an operational Mental Wealth metric. The breadth of conceptual foundations to be considered is extensive, and there may be a lack of agreement on the appropriate tools for its measurement. While variability across current measurement approaches in social resources, wellbeing and mental assets contributes to the difficulty creating a holistic and generic metric, these variations are now clearer. The operationalisation of the Mental Wealth metric will require comprehensive mapping of the elements to be included against the data available.

Measuring, Modeling, and Forecasting the Mental Wealth of Nations.

The COVID-19 pandemic has exposed the deep links and fragility of economic, health and social systems. Discussions of reconstruction include renewed interest in moving beyond GDP and recognizing "human capital", "brain capital", "mental capital", and "wellbeing" as assets fundamental to economic reimagining, productivity, and prosperity. This paper describes how the conceptualization of Mental Wealth provides an important framing for measuring and shaping social and economic renewal to underpin healthy, productive, resilient, and thriving communities. We propose a transdisciplinary application of systems modeling to forecast a nation's Mental Wealth and understand the extent to which policy-mediated changes in economic, social, and health sectors could enhance collective mental health and wellbeing, social cohesion, and national prosperity. Specifically, simulation will allow comparison of the projected impacts of a range of cross-sector strategies (education sector, mental health system, labor market, and macroeconomic reforms) on GDP and national Mental Wealth, and provide decision support capability for future investments and actions to foster Mental Wealth. Finally, this paper introduces the Mental Wealth Initiative that is harnessing complex systems science to examine the interrelationships between social, commercial, and structural determinants of mental health and wellbeing, and working to empirically challenge the notion that fostering universal social prosperity is at odds with economic and commercial interests.

Measuring, Modeling, and Forecasting the Mental Wealth of Nations

The COVID-19 pandemic has exposed the deep links and fragility of economic, health and social systems. Discussions of reconstruction include renewed interest in moving beyond GDP and recognizing “human capital”, “brain capital”, “mental capital”, and “wellbeing” as assets fundamental to economic reimagining, productivity, and prosperity. This paper describes how the conceptualization of Mental Wealth provides an important framing for measuring and shaping social and economic renewal to underpin healthy, productive, resilient, and thriving communities. We propose a transdisciplinary application of systems modeling to forecast a nation's Mental Wealth and understand the extent to which policy-mediated changes in economic, social, and health sectors could enhance collective mental health and wellbeing, social cohesion, and national prosperity. Specifically, simulation will allow comparison of the projected impacts of a range of cross-sector strategies (education sector, mental health system, labor market, and macroeconomic reforms) on GDP and national Mental Wealth, and provide decision support capability for future investments and actions to foster Mental Wealth. Finally, this paper introduces the Mental Wealth Initiative that is harnessing complex systems science to examine the interrelationships between social, commercial, and structural determinants of mental health and wellbeing, and working to empirically challenge the notion that fostering universal social prosperity is at odds with economic and commercial interests.

Duration of Acute Kidney Injury and In-Hospital Mortality in Elder Patients with Severe COVID-19: A Retrospective Cohort Study.

Background: Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients. Methods: We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI. Results: In total, 107 patients were included in the final analysis. The mean age was 70 (64-78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, and 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% (n = 11) for patients without AKI, 72.7% (n = 8) for patients with transient AKI, and 86.5% (n = 32) for patients with persistent AKI (P < 0.001). Kaplan-Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank P < 0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (hazard ratio [HR] = 2.582; 95% CI: 1.025-6.505; P = 0.044; and HR = 6.974; 95% CI: 3.334-14.588; P < 0.001). Conclusions: AKI duration can be an important predictive parameter in elder patients suffering from COVID-19 and are admitted to ICU. Among these patients, those exhibiting persistent AKI have a lower in-hospital survival rate than those with transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.

Impact of a pharmaceutical care service for patients with rheumatoid arthritis using a customised mobile device (the PROUD trial): study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) generally requires lifelong treatment; however, its medication complexity might affect non-adherence. Pharmacist-led telehealth services were as effective as face-to-face services and reduced potential side effects in outpatients with chronic diseases. This study aims to analyse the effect of a telepharmacy service with a customised mobile device in comparison with the usual pharmacist service on the humanistic and clinical outcomes in patients with RA. METHODS AND ANALYSIS: The study is designed as a prospective, randomised, open-label, and controlled trial to compare the humanistic and clinical outcomes of the pharmaceutical care service with monthly telecommunications and a customised mobile application (telepharmacy care group) against the usual service by community pharmacists (usual care group) in 256 patients with RA and prescribed at least one of the disease-modifying antirheumatic drugs. Participants will be recruited from a tertiary hospital in Republic of Korea with written informed consent. The primary outcome will be the changes in health-related quality of life as measured by the Korean version of the EuroQoL's five-dimensional questionnaire at 6 months compared with baseline. The secondary outcomes will be the changes in the following: scores of the Korean version of the Compliance Questionnaire-Rheumatology and medication knowledge at 3 and 6 months compared with baseline; scores of the Korean version of the Pharmacy Service Questionnaire at 6 months compared with baseline; clinical parameters such as erythrocyte sedimentation rate, C reactive protein level, and pain score at 3 and 6 months compared with baseline; frequency of acute care utilisation over 6 months. Analysis will be carried out with intent-to-treat and per-protocol principles. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Daegu Catholic University Medical Center (IRB no. CR-21-082-L, 14 July 2021). The study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: KCT0006508.

Optimizing Strategies for Improving Mental Health in Victoria, Australia during the COVID-19 Era: A System Dynamics Modelling Study.

The ongoing COVID-19 pandemic has impacted the mental health of populations and highlighted the limitations of mental health care systems. As the trajectory of the pandemic and the economic recovery are still uncertain, decision tools are needed to help evaluate the best interventions to improve mental health outcomes. We developed a system dynamics model that captures causal relationships among population, demographics, post-secondary education, health services, COVID-19 impact, and mental health outcomes. The study was conducted in the Australian state of Victoria. The model was calibrated using historical data and was stratified by age group and by geographic remoteness. Findings demonstrate that the most effective intervention combination includes economic, social, and health sector initiatives. Assertive post-suicide attempt care is the most impactful health sector intervention, but delaying implementation reduces the potency of its impact. Some evidence-based interventions, such as population-wide community awareness campaigns, are projected to worsen mental health outcomes when implemented on their own. Systems modelling offers a powerful decision-support tool to test alternative strategies for improving mental health outcomes in the Victorian context.

Early Mental Health and Quality of Life in Discharged Patients With COVID-19.

Aim: This study aimed to analyze the early mental health (MH) and quality of life (QoL) of discharged patients with coronavirus disease 2019 (COVID-19), which can provide a scientific basis for the further development of intervention programs. Methods: In total, 108 subjects participated in this study, including an experimental group (90 patients diagnosed with COVID-19 from March to April 2020 and hospitalized in Wuhan China Resources & WISCO General Hospital, Wuhan, China, 83.3%) and a control group (18 healthy participants, 16.7%). Their MH and QoL were measured through the 12-item Short Form Health Survey version 2 (SF-12v2), the Self-rating anxiety scale (SAS), the Self-rating depression scale (SDS), and the International Physical Activity Questionnaire (IPAQ). The results of questionnaires were compared between these two groups. Results: (1) Comparison of anxiety status: among 90 discharged patients with COVID-19, 30 patients (33.3%) had a state of anxiety. Compared with healthy participants and the general population, patients with COVID-19 in the early stages of discharge had a higher incidence of anxiety and more severe anxiety symptoms (P < 0.05). (2) Comparison of depression status: among 90 discharged patients with COVID-19, 29 patients (32.2%) had a state of depression. Compared with healthy participants and the general population, patients with COVID-19 in the early stages of discharge had a higher incidence of depression and more severe depression symptoms (P < 0.05). (3) Comparison of QoL: 78 patients (86.7%) presented a decrease in physical health-related quality of life (HRQoL) and 73 patients (81.1%) presented a decrease in psychology-related QoL. The SF-12v2 physical component summary (PCS) and the SF-12v2 mental component summary (MCS) of patients were significantly lower than those of healthy people, especially in physical function (PF), vitality (VT), social function (SF), and mental health (MH) (all P < 0.05). (4) Gender differences in mental health and the QoL among patients with COVID-19: women had more severe anxiety/depression symptoms than men (P < 0.05). The scores of women in all dimensions of SF-12V2 were lower than those of men, and there were statistically significant differences between the two groups in PCS, PF, general health (GH), VT, and role-emotional (RE) (P < 0.05). Conclusion: During the early phase after being discharged, patients with COVID-19 might experience negative emotions, such as anxiety or depression, and also problems with reduced QoL, especially among female patients. Therefore, an intervention plan should focus on strengthening psychological condition and improving physical function, and gender-specific rehabilitation programmes should be adapted to improve psychological status and QoL.

Which Social, Economic, and Health Sector Strategies Will Deliver the Greatest Impacts for Youth Mental Health and Suicide Prevention? Protocol for an Advanced, Systems Modelling Approach.

Background: Current global challenges are generating extensive social disruption and uncertainty that have the potential to undermine the mental health, wellbeing, and futures of young people. The scale and complexity of challenges call for engagement with systems science-based decision analytic tools that can capture the dynamics and interrelationships between physical, social, economic, and health systems, and support effective national and regional responses. At the outset of the pandemic mental health-related systems models were developed for the Australian context, however, the extent to which findings are generalisable across diverse regions remains unknown. This study aims to explore the context dependency of systems modelling insights. Methods: This study will employ a comparative case study design, applying participatory system dynamics modelling across eight diverse regions of Australia to answer three primary research questions: (i) Will current regional differences in key youth mental health outcomes be exacerbated in forward projections due to the social and economic impacts of COVID-19?; (ii) What combination of social policies and health system strengthening initiatives will deliver the greatest impacts within each region?; (iii) To what extent are optimal strategic responses consistent across the diverse regions? We provide a detailed technical blueprint as a potential springboard for more timely construction and deployment of systems models in international contexts to facilitate a broader examination of the question of generalisability and inform investments in the mental health and wellbeing of young people in the post COVID-19 recovery. Discussion: Computer simulation is known as the third pillar of science (after theory and experiment). Simulation allows researchers and decision makers to move beyond what can be manipulated within the scale, time, and ethical limits of the experimental approach. Such learning when achieved collectively, has the potential to enhance regional self-determination, help move beyond incremental adjustments to the status quo, and catalyze transformational change. This research seeks to advance efforts to establish regional decision support infrastructure and empower communities to effectively respond. In addition, this research seeks to move towards an understanding of the extent to which systems modelling insights may be relevant to the global mental health response by encouraging researchers to use, challenge, and advance the existing work for scientific and societal progress.

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN­specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non­COVID-19 controls revealed a lack of type I IFN­stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN­specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN­specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

Coronavirus disease 2019 (COVID-19) complicated with acute myocardial infarction: etiology and nursing experience of three case reports.

Coronavirus disease 2019 (COVID-19), an acute infectious disease, which is characterized by influenza, fever, cough and dyspnea. Up to now, the pathogenic mechanism and radical cure treatment for COVID-19 are still unknown. However, COVID-19 could lead to pneumonia, multiple organ failure and even death with disease development. During the period of February 10 and March 26, 2020, we admitted and treated three COVID-19 patients complicated with acute myocardial infarction. As we all know, acute myocardial infarction is a kind of disease that induces myocardial ischemia necrosis and leads to high mortality. Through the three COVID-19 patients complicated with acute myocardial infarction, we have strengthened our nursing experience. Thus, we wish to share our nursing experience with these cases by analyzing the etiology of three patients with coronavirus disease 2019 (COVID-19) complicated with acute myocardial infarction in this paper. First, we retrospectively analyzed the clinical data, including patient complaints, diagnosis, treatment, and prognosis, of three patients with COVID-19 complicated with acute myocardial infarction admitted to Ward II, Department of Infectious Diseases III, Huoshenshan Hospital, Wuhan, Hubei Province, China, between February 10 and March 26, 2020. Then, we searched for relevant literature, analyzed etiology, and summarized the nursing measures taken. For COVID-19 patients with a high risk of acute myocardial infarction, nurses should stay vigilant, closely monitor any change in condition, and implement early measures to maintain vital signs and enable timely visits with specialists. Finally, we importantly found that these nursing measures are keys to managing the patient's condition, improving patient outcomes, and increasing the chance of treatment success.

Supporting Clinicians to Use Technology to Deliver Highly Personalized and Measurement-Based Mental Health Care to Young People: Protocol for an Evaluation Study.

BACKGROUND: Australia's mental health care system has long been fragmented and under-resourced, with services falling well short of demand. In response, the World Economic Forum has recently called for the rapid deployment of smarter, digitally enhanced health services to facilitate effective care coordination and address issues of demand. The University of Sydney's Brain and Mind Centre (BMC) has developed an innovative digital health solution that incorporates 2 components: a highly personalized and measurement-based (data-driven) model of youth mental health care and a health information technology (HIT) registered on the Australian Register of Therapeutic Goods. Importantly, research into implementation of such solutions considers education and training of clinicians to be essential to adoption and optimization of use in standard clinical practice. The BMC's Youth Mental Health and Technology Program has subsequently developed a comprehensive education and training program to accompany implementation of the digital health solution. OBJECTIVE: This paper describes the protocol for an evaluation study to assess the effectiveness of the education and training program on the adoption and optimization of use of the digital health solution in service delivery. It also describes the proposed tools to assess the impact of training on knowledge and skills of mental health clinicians. METHODS: The evaluation study will use the Kirkpatrick Evaluation Model as a framework with 4 levels of analysis: Reaction (to education and training), Learning (knowledge acquired), Behavior (practice change), and Results (client outcomes). Quantitative and qualitative data will be collected using a variety of tools, including evaluation forms, pre- and postknowledge questionnaires, skill development and behavior change scales, as well as a real-time clinical practice audit. RESULTS: This project is funded by philanthropic funding from Future Generation Global. Ethics approval has been granted via Sydney Local Health District's Human Research Ethics Committee. At the time of this publication, clinicians and their services were being recruited to this study. The first results are expected to be submitted for publication in 2021. CONCLUSIONS: The education and training program teaches clinicians the necessary knowledge and skills to assess, monitor, and manage complex needs; mood and psychotic syndromes; and trajectories of youth mental ill-health using a HIT that facilitates a highly personalized and measurement-based model of care. The digital health solution may therefore guide clinicians to help young people recover low functioning associated with subthreshold diagnostic presentations and prevent progression to more serious mental ill-health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/24697.

Effect of an online healthy lifestyle psychoeducation programme to improve cardiometabolic outcomes and affective symptoms in youth receiving mental health care: study protocol for a pilot clinical trial.

INTRODUCTION: Worsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort. METHODS AND ANALYSIS: This 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16-25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep-wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep-wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson's or Spearman's correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures. ETHICS AND DISSEMINATION: This pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12620000772943, Date 28 August 2020.

What is the patient experience of surgical care during the coronavirus disease 2019 (COVID-19) pandemic? A mixed-methods study at a single institution.

BACKGROUND: The coronavirus disease 2019 outbreak has spread worldwide and has resulted in hospital restrictions. The perceived impact of these practices on patients undergoing essential surgeries is less understood. METHODS: Adult (≥18 years) patients who underwent medically necessary surgical procedures spanning multiple surgical specialties from March 23, 2020, to April 24, 2020, during the coronavirus disease 2019 pandemic were identified as eligible for a phone survey. Survey responses were analyzed using a mixed-methods approach involving descriptive statistics and thematic analysis of coded and annotated survey results. RESULTS: Of the 212 patients who underwent medically necessary surgical procedures during the coronavirus disease 2019 pandemic, the majority of these patients were male (61.3%), White (83.5%), married or with a domestic partner (68.9%), and underwent oncologic procedures (69.3%). Of the 46 patients (21.7%) who completed the survey, the majority of these patients indicated that coronavirus disease 2019 pandemic restrictions had no impact on their inpatient hospital stay and were satisfied with their decision to proceed with surgery. Severity of patient condition (44.4%), the risk/benefit discussion with the surgeon (24.4%), and coronavirus disease 2019 education and testing (19.5%) were the most important factors in proceeding with surgery during the pandemic; 34.4% of patients said their inpatient postoperative course was negatively affected by the lack of visitors. CONCLUSION: Medically necessary, time-sensitive surgical procedures, as determined by the surgeon, can be performed during a pandemic with good patient satisfaction provided there is an appropriate discussion between the surgeon and patient about the risks and benefits.

The antigenic anatomy of SARS-CoV-2 receptor binding domain.

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 µg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.