Aptamer-based nanointerferometer enables amplification-free ultrasensitive detection and differentiation of SARS-CoV-2 variants.

The state-of-the-art SARS-CoV-2 detection methods include qRT-PCR and antibody-based lateral flow assay (LFA) point-of-care tests. Despite the high sensitivity and selectivity, qRT-PCR is slow, expensive and needs well-trained operators. On the other extreme, LFA suffers from low sensitivity albeit its fast detection speed, low detection cost and ease of use. Therefore, the continuing COVID-19 pandemic calls for a SARS-CoV-2 detection method that is rapid, convenient and cost-effective without compromise in sensitivity. Here we provide a proof-of-principle demonstration of an optimized aptamer-based nanointerferometer that enables rapid and amplification-free detection of SARS-CoV-2 spike protein-coated pseudovirus directly from human saliva with the limit of detection (LOD) of about 400 copies per mL. This LOD is on par with that of qRT-PCR, making it 1000 to 100,000-fold more sensitive than commercial LFA tests. Using various combinations of negative selections during the screens for the aptamer targeting the receptor binding domain of the spike protein of SARS-CoV-2, we isolated two aptamers that can distinguish the Omicron and Delta variants. Integrating these two aptamers with LFA strips or the nanointerferometer sensors allows both detection and differentiation of the Omicron and Delta variants which has the potential to realize rapid triage of patients infected different SARS-CoV-2 variants.

Human antibody BD-218 has broad neutralizing activity against concerning variants of SARS-CoV-2.

As SARS-CoV-2 variants of concern (VOC) reduce the effectiveness of existing anti-COVID therapeutics, it is increasingly critical to identify highly potent neutralizing antibodies (nAbs) that bind to conserved regions across multiple variants, especially beta, delta, and omicron variants. Using single-cell sequencing with biochemical methods and pseudo-typed virus neutralization experiments, here we report the characterization of a potent nAb BD-218, identified from an early screen of patients recovering from the original virus. We have determined the cryo-EM structure of the BD-218/spike protein complex to define its epitope in detail, which revealed that BD-218 interacts with a novel epitope on the receptor-binding domain (RBD) of the spike protein. We concluded that BD-218 is a highly effective and broadly active nAb against SARS-CoV-2 variants with promising potential for therapeutic development.

COVID-19 Pandemic and the Operation of a Tertiary Hospital in Tianjin-The Impact of Internet Healthcare on Hospital Business Indicators.

Objective: To explore the impact of the COVID-19 pandemic on hospital business and the contribution of Internet healthcare to hospital operations during the epidemic by analyzing the degree of impact on major business indicators. Methods: The three-year period from 2019 to 2021 was compared and analyzed, and the main medical business indicators such as outpatient and emergency visits, inpatients, operations, patient improvement rate, cure rate and fatality rate in tertiary hospitals were compared and analyzed, and the impact of the epidemic on medical services and hospital operation was analyzed. degree and the impact of Internet medical development on medical service capacity. Results: During the outbreak of COVID-19, the number of hospital outpatient and emergency visits, inpatients, and operations decreased significantly; after the normalization of the epidemic, the main medical business indicators such as outpatient and emergency visits, inpatients, and operations gradually returned to pre-epidemic levels; patient improvement rate, the cure rate and mortality rate and other indicators did not change significantly. During the epidemic period, the number of visits to the Internet outpatient clinic has increased significantly, which has significantly improved the hospital's medical service capacity. Conclusion: With the normalization of epidemic prevention and control, the main business indicators of Tianjin tertiary hospitals have gradually recovered. The operation of Internet medical care during the epidemic has changed the management and operation mode of the hospital to a certain extent, improved the main business indicators of the hospital, and eased the pressure on the hospital's economic operation.

Acceptance of the COVID-19 vaccine based on the health belief model: a multicenter national survey among medical care workers in China.

Vaccine uptake rate is crucial for herd immunity. Medical care workers (MCWs) can serve as ambassadors of COVID-19 vaccine acceptance. This study aimed to assess MCWs' willingness to receive the COVID-19 vaccine, and to explore the factors affecting COVID-19 vaccination acceptance. A multicenter study among medical care workers was conducted in seven selected hospitals from seven geographical territories of China, and data were collected on sociodemographic characteristics, vaccine hesitancy, and health beliefs on COVID-19 vaccination among participants. Univariate and multivariate logistic regression models were performed to explore the correlations between individual factors and the acceptance of the COVID-19 vaccine. Among the 2681 subjects, 82.5% of the participants were willing to accept the COVID-19 vaccination. Multivariate regression analyses revealed that individuals with more cues to action about the vaccination, higher level of confidence about the vaccine, and higher level of trust in the recommendations of COVID-19 vaccine from the government and the healthcare system were more likely to get the COVID-19 vaccine. In contrast, subjects with higher level of perceived barriers and complacency were less likely to accept the COVID-19 vaccine. Overall, MCWs in China showed a high willingness to get the COVID-19 vaccine. The governmental recommendation is an important driver and lead of vaccination. Relevant institutions could increase MCWs' willingness to COVID-19 vaccines by increasing MCWs' perception of confidence about COVID-19 vaccines and cues to action through various strategies and channels. Meanwhile, it can also provide evidence in similar circumstances in the future to develop vaccine promotion strategies.

Mixed-Reality-Enhanced Human–Robot Interaction with an Imitation-Based Mapping Approach for Intuitive Teleoperation of a Robotic Arm-Hand System

This paper presents an integrated mapping of motion and visualization scheme based on a Mixed Reality (MR) subspace approach for the intuitive and immersive telemanipulation of robotic arm-hand systems. The effectiveness of different control-feedback methods for the teleoperation system is validated and compared. The robotic arm-hand system consists of a 6 Degrees-of-Freedom (DOF) industrial manipulator and a low-cost 2-finger gripper, which can be manipulated in a natural manner by novice users physically distant from the working site. By incorporating MR technology, the user is fully immersed in a virtual operating space augmented by real-time 3D visual feedback from the robot working site. Imitation-based velocity-centric motion mapping is implemented via the MR subspace to accurately track operator hand movements for robot motion control and enables spatial velocity-based control of the robot Tool Center Point (TCP). The user control space and robot working space are overlaid through the MR subspace, and the local user and a digital twin of the remote robot share the same environment in the MR subspace. The MR-based motion and visualization mapping scheme for telerobotics is compared to conventional 2D Baseline and MR tele-control paradigms over two tabletop object manipulation experiments. A user survey of 24 participants was conducted to demonstrate the effectiveness and performance enhancements enabled by the proposed system. The MR-subspace-integrated 3D mapping of motion and visualization scheme reduced the aggregate task completion time by 48% compared to the 2D Baseline module and 29%, compared to the MR SpaceMouse module. The perceived workload decreased by 32% and 22%, compared to the 2D Baseline and MR SpaceMouse approaches.

[Mental Health Status and Its Influencing Factors among College Students during the Epidemic of Coronavirus Disease 2019:A Multi-center Cross-sectional Study].

Objective To measure the prevalence of mental health symptoms and identify the associated factors among college students at the beginning of coronavirus disease 2019(COVID-19)outbreak in China. Methods We carried out a multi-center cross-sectional study via snowball sampling and convenience sampling of the college students in different areas of China.The rates of self-reported depression,anxiety,and stress and post-traumatic stress disorder(PTSD)were assessed via the 21-item Depression-Anxiety-Stress Scale(DASS-21)and the 6-item Impact of Event Scale-Revised(IES-6),respectively.Covariates included sociodemographic characteristics,health-related data,and information of the social environment.Data pertaining to mental health service seeking were also collected.Multivariate Logistic regression analyses were performed to identify the risk factors. Results A total of 3641 valid questionnaires were collected from college students.At the beginning of the COVID-19 outbreak,535(14.69%)students had negative emotions,among which 402(11.04%),381(10.49%),and 171(4.90%)students had the symptoms of depression,anxiety,and stress,respectively.Meanwhile,1245(34.19%)college students had PTSD.Among the risk factors identified,male gender was associated with a lower likelihood of reporting depression symptoms(AOR=0.755,P=0.037],and medical students were at higher risk of depression and stress symptoms than liberal arts students(AOR=1.497,P=0.003;AOR=1.494,P=0.045).Family support was associated with lower risks of negative emotions and PTSD in college students(AOR=0.918,P<0.001;AOR=0.913,P<0.001;AOR=0.899,P<0.001;AOR=0.971,P=0.021). Conclusions College students were more sensitive to public health emergencies,and the incidence of negative emotions and PTSD was significantly higher than that before the outbreak of COVID-19.More attention should be paid to female college students who were more likely to develop negative emotions.We should strengthen positive and proper propaganda via mass media and help college students understand the situation and impact of COVID-19.Furthermore,we should enhance family support for college students.The government and relevant agencies need to provide appropriate mental health services to the students under similar circumstances to avoid the deterioration of their mental well-being.

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Prevalence and Predictors of PTSD During the Initial Stage of COVID-19 Epidemic among Female College Students in China.

BACKGROUND: College students are vulnerable and may experience high stress due to COVID-19, especially girls. This study aims to identify posttraumatic stress disorder (PTSD) and related factors among the target population during the initial phases of the COVID-19 pandemic. METHODS: In the initial phase of COVID-19 epidemic (February 23 to March 5, 2020), 2205 female college students from six provinces in mainland China were enrolled in this study and completed the online survey about the cognitive status of COVID-19, including the Impact of Event Scale-6, the Multidimensional Perceived Social Support Scale and a self-developed 10-item Perceived threat scale. Univariate and multivariate logistic regression were performed using SPSS software to explore the determinants of PTSD symptoms. RESULTS: PTSD symptoms were prevalent in female college students, and 34.20% met the cut-off for PTSD. Self-reported fair or poor health (AOR = 1.78, 95% CI: 1.22-2.59), high concern about COVID-19 (AOR = 1.66, 95% CI: 1.35-2.03), beliefs that "COVID-19 can cause a global outbreak" (AOR = 1.26, 95% CI: 1.02-1.56), the perception of "risk of infection" (AOR = 2.46, 95% CI: 2.16-2.81), beliefs that "closed management" and "COVID-19 as a public health emergency of international concern" would have an impact, and the fear of "impact on life planning" were all positively associated with PTSD (AOR = 1.37, 1.22, and 1.29, respectively); however, perceived social support from family (AOR = 0.81, 95% CI: 0.70-0.93) was negatively associated with PTSD. Among the significant variables at the bivariate level, multivariate logistic regression revealed that the greatest protector for PTSD was the high knowledge score (AOR = 0.73, 95% CI: 0.60-0.90), while had confirmed cases among relatives and friends (AOR = 7.70, 95% CI: 1.28-46.25) was the strongest predictor of PTSD. CONCLUSIONS: In summary, PTSD symptoms were prevalent among female college students in China during the COVID-19 epidemic. Targeting vulnerable populations to improve their knowledge about COVID-19 and create an atmosphere of social support would be beneficial. Moreover, the joint efforts from family, school administrators, and policymakers are essential to improve the mental health of the female students during the COVID-19 epidemic.

Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to more than 270 million infections and 5.3 million of deaths worldwide. Several major variants of SARS-CoV-2 have emerged and posed challenges in controlling the pandemic. The recently occurred Omicron variant raised serious concerns about reducing the efficacy of vaccines and neutralization antibodies due to its vast mutations. We have modelled the complex structure of the human ACE2 protein and the receptor binding domain (RBD) of Omicron Spike protein (S-protein), and conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron RBD binds more strongly to the human ACE2 protein than the original strain. The mutations at the ACE2-RBD interface enhance the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.

Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to the receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals, predicted the structures of ACE2-RBD complexes by homology modeling, and refined the complexes using molecular dynamics simulation. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The analysis outcomes suggest that the ACE2 of bovine, cat, and panda form strong binding interactions with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse, and civet, the ACE2 proteins interact weakly with RBD.

Convalescent plasma is of limited clinical benefit in critically ill patients with coronavirus disease-2019: a cohort study.

BACKGROUND: Recently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion. METHODS: In this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan-Meier survival analysis. RESULTS: Data analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5-74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085). CONCLUSION: In our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation.

Mindfulness-based online intervention on mental health and quality of life among COVID-19 patients in China: an intervention design.

BACKGROUND: COVID-19 can lead to increased psychological symptoms such as post-traumatic stress disorder (PTSD), depression, and anxiety among patients with COVID-19. Based on the previous mindfulness-based interventions proved to be effective, this protocol reports a design of a randomized controlled trial aiming to explore the efficacy and possible mechanism of a mindful living with challenge (MLWC) intervention developed for COVID-19 survivors in alleviating their psychological problems caused by both the disease and the pandemic. METHODS: In April 2021, more than 1600 eligible participants from Hubei Province of China will be assigned 1:1 to an online MLWC intervention group or a waitlist control group. All participants will be asked to complete online questionnaires at baseline, post-program, and 3-month follow-up. The differences of mental health status (e.g. PTSD) and physical symptoms including fatigue and sleeplessness between the COVID-19 survivors who receiving the online MLWC intervention and the control group will be assessed. In addition, the possible mediators and moderators of the link between the MLWC intervention and target outcomes will be evaluated by related verified scales, such as the Five Facets Mindfulness Questionnaire. Data will be analyzed based on an intention-to-treat approach, and SPSS software will be used to perform statistical analysis. DISCUSSION: The efficacy and potential mechanism of MLWC intervention in improving the quality of life and psychological status of COVID-19 survivors in China are expected to be reported. Findings from this study will shed light on a novel and feasible model in improving the psychological well-being of people during such public health emergencies. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000037524; Registered on August 29, 2020, http://www.chictr.org.cn/showproj.aspx?proj=60034 .

Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy.

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.

Psychological impact of COVID-19 on medical care workers in China.

BACKGROUND: Medical care workers experienced unprecedented levels of workload and pressure since the outbreak of coronavirus disease 2019 (COVID-19). Little is known about its exact impact on medical care workers and related factors in China. This study aims to identify the psychological impact of COVID-19 on medical care workers in China. METHODS: From February 23 to March 5, 2020, a cross-sectional survey was conducted among 863 medical care workers from seven provinces in China using standard questionnaires measuring adverse psychological outcomes including Impact of Event Scale-6 (IES-6), Depression, Anxiety and Stress Scale(DASS)and related psychosocial factors like perceived threat, social support and coping strategies. Exploratory Factor analysis was performed to identify the dimensions of perceived threat by study participants. Multivariate regression was used to examine the determinants of adverse psychological outcomes. RESULTS: Posttraumatic stress (PTS) were prevalent in this sample of health care professionals, and 40.2% indicated positive screens for significant posttraumatic stress disorder symptoms. The proportion of having mild to extremely severe symptoms of depression, anxiety and stress were 13.6, 13.9 and 8.6%, respectively. Perceived threat and passive coping strategies were positively correlated to PTS and DASS scores, while perceived social support and active coping strategies were negatively correlated to DASS scores. Nurses were more likely to be anxious than others among medical care workers during the COVID-19 epidemic. CONCLUSIONS: Adverse psychological symptoms were prevalent among medical care workers in China during the COVID-19 epidemic. Screening for adverse psychological outcomes and developing corresponding preventive measures would be beneficial in decreasing negative psychological outcomes.

SARS-CoV-2 and viral sepsis: observations and hypotheses.

Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

Novel Coronavirus International Public Health Emergency: Guidance on Radiation Oncology Facility Operation.

PURPOSE: The current situation of coronavirus disease 2019 (COVID-19) is rapidly evolving. Radiation therapy facilities are places of concentrated patient interactions. Oncology patients with immunosuppression are at a higher risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and easily developing severe postinfection events during the SARS-CoV-2 outbreaks. This review aimed to provide some guidance and be a reference to medical professionals in radiation oncology so that they may provide oncology patients with safe and high-quality care. METHODS AND MATERIALS: This paper discussed how radiation therapy departments or centers can most effectively respond to this public health emergency through summarizing the procedures and protocols implemented at hospitals in ShenZhen, China. RESULTS: The impact of the virus in radiation therapy facilities can be mitigated and managed with appropriate and timely implementation of infection control procedures and protocols. CONCLUSIONS: In the face of acute infectious disease, it is critical to maintain strict infectious disease control procedures and to create a clear clinical workflow protocol to best protect medical staff and patients from the effect of acute infectious diseases.