Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19.

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies (mAbs) in the treatment of coronavirus infectious disease 2019 (COVID-19). The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied. Immunoglobulin M (IgM) appeared earlier and lasted for a short time, while immunoglobulin G (IgG) appeared later and lasted longer. IgM tests can be used for early diagnosis of COVID-19, and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons. The combination of antibody testing and nucleic acid testing, which complement each other, can improve the diagnosis rate of COVID-19. Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients. COVID-19 convalescent plasma, highly concentrated immunoglobulin, and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products. Due to the continuous emergence of mutated strains of the novel coronavirus, especially omicron, its immune escape ability and infectivity are enhanced, making the effects of authorized products reduced or invalid. Therefore, the optimal application of anti-SARS-CoV-2 antibody products (especially anti-SARS-CoV-2 specific mAbs) is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Telemedicine management of type 2 diabetes mellitus in obese and overweight young and middle-aged patients during COVID-19 outbreak: A single-center, prospective, randomized control study.

OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic severely affected the disease management of patients with chronic illnesses such as type 2 diabetes mellitus (T2DM). This study aimed to assess the effect of telemedicine management of diabetes in obese and overweight young and middle-aged patients with T2DM during the COVID-19 pandemic. METHODS: A single-center randomized control study was conducted in 120 obese or overweight (body mass index [BMI] ≥ 24 kg/m2) young and middle-aged patients (aged 18-55 years) with T2DM. Patients were randomly assigned to the intervention (telemedicine) or control (conventional outpatient clinic appointment) group. After baseline assessment, they were home isolated for 21 days, received diet and exercise guidance, underwent glucose monitoring, and followed up for 6 months. Glucose monitoring and Self-Rating Depression Scale (SDS) scores were evaluated at 22 days and at the end of 3 and 6 months. RESULTS: Ninety-nine patients completed the 6-month follow-up (intervention group: n = 52; control group: n = 47). On day 22, the fasting blood glucose (FBG) level of the intervention group was lower than that of the control group (p < 0.05), and the control group's SDS increased significantly compared with the baseline value (p < 0.05). At the end of 3 months, glycated hemoglobin (HbA1c) and FBG levels in the intervention group decreased significantly compared with those in the control group (p < 0.01). At the end of 6 months, the intervention group showed a significant decrease in postprandial blood glucose, triglyceride, and low-density lipoprotein cholesterol levels as well as waist-to-hip ratio compared with the control group (p < 0.05); moreover, the intervention group showed lower SDS scores than the baseline value (p < 0.05). Further, the intervention group showed a significant reduction in BMI compared with the control group at the end of 3 and 6 months (p < 0.01). CONCLUSION: Telemedicine is a beneficial strategy for achieving remotely supervised blood glucose regulation, weight loss, and depression relief in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04723550.

A Protein Microarray-Based Respiratory Viral Antigen Testing Platform for COVID-19 Surveillance.

High-throughput and rapid screening testing is highly desirable to effectively combat the rapidly evolving COVID-19 pandemic co-presents with influenza and seasonal common cold epidemics. Here, we present a general workflow for iterative development and validation of an antibody-based microarray assay for the detection of a respiratory viral panel: (a) antibody screening to quickly identify optimal reagents and assay conditions, (b) immunofluorescence assay design including signal amplification for low viral titers, (c) assay characterization with recombinant proteins, inactivated viral samples and clinical samples, and (d) multiplexing to detect a panel of common respiratory viruses. Using RT-PCR-confirmed SARS-CoV-2 positive and negative pharyngeal swab samples, we demonstrated that the antibody microarray assay exhibited a clinical sensitivity and specificity of 77.2% and 100%, respectively, which are comparable to existing FDA-authorized antigen tests. Moreover, the microarray assay is correlated with RT-PCR cycle threshold (Ct) values and is particularly effective in identifying high viral titers. The multiplexed assay can selectively detect SARS-CoV-2 and influenza virus, which can be used to discriminate these viral infections that share similar symptoms. Such protein microarray technology is amenable for scale-up and automation and can be broadly applied as a both diagnostic and research tool.

Homogeneous surrogate virus neutralization assay to rapidly assess neutralization activity of anti-SARS-CoV-2 antibodies.

The COVID-19 pandemic triggered the development of numerous diagnostic tools to monitor infection and to determine immune response. Although assays to measure binding antibodies against SARS-CoV-2 are widely available, more specific tests measuring neutralization activities of antibodies are immediately needed to quantify the extent and duration of protection that results from infection or vaccination. We previously developed a 'Serological Assay based on a Tri-part split-NanoLuc® (SATiN)' to detect antibodies that bind to the spike (S) protein of SARS-CoV-2. Here, we expand on our previous work and describe a reconfigured version of the SATiN assay, called Neutralization SATiN (Neu-SATiN), which measures neutralization activity of antibodies directly from convalescent or vaccinated sera. The results obtained with our assay and other neutralization assays are comparable but with significantly shorter preparation and run time for Neu-SATiN. As the assay is modular, we further demonstrate that Neu-SATiN enables rapid assessment of the effectiveness of vaccines and level of protection against existing SARS-CoV-2 variants of concern and can therefore be readily adapted for emerging variants.

Viral Governance: How Unilateral U.S. Sanctions Changed the Rules of Financial Capitalism

This article presents how global governance went viral as its targets moved from sovereign to corporate entities and its source from multilateral financial institutions to domestic U.S. institutions. It argues that viral governance describes how the United States rewrote global rules through its sanctions program first against Iran, then against Iran-affiliated global banks and businesses, and finally against the daily compliance practices of global money, information, and technology flows in general. Utilizing over 150 interviews with international experts in the field of sanctions and banking, the article describes the recursive process that led the U.S. government to assume global regulatory powers and to initiate deglobalization in its trade war against the European Union and China. The article concludes that viral governance perpetuates crises, whereas multilateral governance seeks to extinguish crises;it operates through sustained legal uncertainty over the jurisdictional limits of the hegemonic power, while multilateral governance seeks to absorb legal uncertainty;it requires the abolition of all regulatory counterpowers, whereas multilateral governance can allow strong states to assume the equality of sovereign powers. [ FROM AUTHOR] Copyright of American Journal of Sociology is the property of University of Chicago and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Mental health & maltreatment risk of children with special educational needs during COVID-19.

BACKGROUND: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment. OBJECTIVE: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk. PARTICIPANTS AND SETTING: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19. METHOD: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19. RESULTS: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ2 = 5.19 p = 0.023). CONCLUSION: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.

Homogeneous Surrogate Virus Neutralization Assay to Rapidly Assess Neutralization Activity of Anti-SARS-CoV-2 Antibodies (preprint)

The COVID-19 pandemic triggered the development of numerous diagnostic tools to monitor infection and to determine immune response. Although assays to measure binding antibodies against SARS-CoV-2 are widely available, more specific tests measuring neutralization activities of antibodies are immediately needed to quantify the extent and duration of protection that results from infection or vaccination. We previously developed a ‘Serological Assay based on a Tri-part split-NanoLuc® (SATiN)’ to detect antibodies that bind to the spike (S) protein of SARS-CoV-2. Herein, we expand on our previous work and describe a reconfigured version of the SATiN assay that can measure neutralization activity of antibodies directly from convalescent or vaccinated sera. The sensitivity is comparable to cell-based pseudovirus neutralization assays but with significantly shorter preparation and assay run time. As the assay is modular, we further demonstrate that Neutralization SATiN (Neu-SATiN) enables rapid assessment of the effectiveness of vaccines and level of protection against existing SARS-CoV-2 variants of concern and can therefore be readily adapted for emerging variants.

Sanctioned countries in the global COVID-19 vaccination campaign: the forgotten 70.

COVAX, the global initiative on COVID-19 vaccines, has set the target of achieving a COVID-19 vaccination coverage of up to 30% of the population of 135 countries in 2 years. Here, we argue that COVAX should anticipate important and unforeseen challenges with regard to sanctioned countries. For those, COVAX needs to provide a higher percentage of the vaccines. Otherwise, the problems of vaccination will linger, risking the advent of new variants and preventing an effective global response in reigning the pandemic under control.

MDRO transmission in acute hospitals during the COVID-19 pandemic.

PURPOSE OF REVIEW: The coronavirus disease (COVID-19) pandemic has resulted in necessary modifications of infection control policies and practices in acute healthcare facilities globally. This is often accompanied by infrastructure modifications, ward redesignations, as well as healthcare staff redeployments and changes to infection prevention and control (IPC) practices. We review the potential for both negative and positive impacts these major changes can have on nosocomial transmission of multidrug-resistant organisms (MDROs). RECENT FINDINGS: Healthcare facilities around the world have reported outbreaks of MDROs during the COVID-19 pandemic. In contrast some centres have reported a decrease in baseline rates due to a number of possible factors. SUMMARY: While implementing crucial preventive measures for COVID-19, is it important to consider any collateral effects of changes in IPC and antimicrobial stewardship program (ASP) practices. The disruption caused to IPC and ASP practices during the pandemic are likely to see a counter intuitive increase in transmission of MDROs.

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.

A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies.

Better diagnostic tools are needed to combat the ongoing COVID-19 pandemic. Here, to meet this urgent demand, we report a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This serological assay, called SATiN, is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in the liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that SATiN has a similar sensitivity to ELISA, and its readouts are consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics, as well as disease and vaccination management.

Knowledge of and attitudes toward COVID-19 among parents of child dental patients during the outbreak

Abstract: The aim of this study was to evaluate the knowledge of and attitudes toward coronavirus disease 2019 (COVID-19) among the parents of child dental patients in Shenzhen during the outbreak. A structured questionnaire containing 10 questions was used, and each question had 2 or 3 possible answers. The parents of children (aged 0-14 years) who visited the dental department of our hospital last year were eligible to participate in this study. A total of 148 parents were interviewed by telephone in February 2020 by research staff. A total of 94.59% of the parents said they paid high attention to COVID-19 and explained it to their children;66.22% thought the dental department environment was more dangerous than other public places;91.89% believed the dental department had a higher risk of virus infection;and 83.78% said they would take their children to a dental department if the children had a severe toothache. Approximately 81.08% of the parents expressed confidence after we informed them about the preventive measures taken in the dental department to ensure safe treatment for their children. In conclusion, all parents were concerned about COVID-19, and most of them had talked about it with their children often. In addition, a considerable percentage of them would not take their children to the dental department even if they had severe dental pain and thought that the dental environment could be more dangerous than other environments. More information about this topic should be delivered to this population.

HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

A Homogeneous Split-Luciferase Assay for Rapid and Sensitive Detection of Anti-SARS CoV-2 Antibodies (preprint)

To meet the urgent demand for better diagnostic tools to combat the ongoing COVID-19 pandemic, we developed a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This assay is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that tNLuc maintains a similar sensitivity to ELISA, while its readouts are highly consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics and disease and vaccination management. 

Trend of Olfactory and Gustatory Dysfunction in COVID-19 Patients in a Quarantine Facility.

BACKGROUND: Olfactory and gustatory dysfunction has been reported as characteristic symptoms of coronavirus disease 2019 (COVID-19). This study evaluated olfactory and gustatory dysfunction in mild COVID-19 patients using validated assessment methods. METHODS: A prospective surveillance study was conducted for mild COVID-19 patients who were isolated at the Gyeonggi International Living and Treatment Support Center (LTSC), Korea. Olfactory function was assessed using the Korean version of the Questionnaire of Olfactory Disorders (QOD) and Cross-Cultural Smell Identification Test (CC-SIT). Gustatory function was assessed using an 11-point Likert scale and 6-n-propylthiouracil, phenylthiocarbamide, and control strips. All patients underwent nasal and oral cavity endoscopic examination. RESULTS: Of the 62 patients at the LTSC, 15 patients (24.2%) complained of olfactory or gustatory dysfunction on admission. Four of 10 patients who underwent functional evaluation did not have general symptoms and 2 were asymptomatic. The mean short version of QOD-negative statements and QOD-visual analogue scale scores were 13 ± 6 and 4.7 ± 3.6, respectively. The mean CC-SIT score was 8 ± 2. No patients showed anatomical abnormalities associated with olfactory dysfunction on endoscopic examination. The mean Likert scale score for function was 8 ± 2, and there were no abnormal lesions in the oral cavity of any patient. CONCLUSIONS: The prevalence of olfactory and gustatory dysfunction was 24.2% in mild COVID-19 patients. All patients had hyposmia due to sensorineural olfactory dysfunction, which was confirmed using validated olfactory and gustatory evaluation methods and endoscopic examination. Olfactory and gustatory dysfunction may be characteristic indicators of mild COVID-19.

COVID-19 from the Perspective of a Gastroenterologist.

The World Health Organization (WHO) declared the worldwide pandemic of Coronavirus disease-2019 (COVID-19) On March 11, 2020, just three months after the first outbreak of COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 in China in December 2019. COVID-19 is a contagious disease that can affect anyone, anytime, anywhere, and has had a huge impact on our lives, including social, economic, educational, and cultural life. In this paper, I would like to explore the issues related to COVID-19 in the gastroenterology and share the experiences of domestic and overseas gastroenterologists, and ultimately to seek ways to effectively prepare for and cope with the pandemic era of COVID-19.

Different outcome of COVID-19 in members of a family.

We report a family cluster of cases of coronavirus disease 2019 (COVID-19), in which three members of the family were exposed to SARS-CoV-2 at the same time, but the disease manifested differently among the three family members. We describe the clinical manifestations, disease progression, and treatment of wife and husband. We also analyze the daughter who was in close contact with patients with COVID-19 but was not infected.

Knowledge of and attitudes toward COVID-19 among parents of child dental patients during the outbreak.

The aim of this study was to evaluate the knowledge of and attitudes toward coronavirus disease 2019 (COVID-19) among the parents of child dental patients in Shenzhen during the outbreak. A structured questionnaire containing 10 questions was used, and each question had 2 or 3 possible answers. The parents of children (aged 0-14 years) who visited the dental department of our hospital last year were eligible to participate in this study. A total of 148 parents were interviewed by telephone in February 2020 by research staff. A total of 94.59% of the parents said they paid high attention to COVID-19 and explained it to their children; 66.22% thought the dental department environment was more dangerous than other public places; 91.89% believed the dental department had a higher risk of virus infection; and 83.78% said they would take their children to a dental department if the children had a severe toothache. Approximately 81.08% of the parents expressed confidence after we informed them about the preventive measures taken in the dental department to ensure safe treatment for their children. In conclusion, all parents were concerned about COVID-19, and most of them had talked about it with their children often. In addition, a considerable percentage of them would not take their children to the dental department even if they had severe dental pain and thought that the dental environment could be more dangerous than other environments. More information about this topic should be delivered to this population.

Early Experience Managing a High-volume Academic Orthopaedic Department During the Coronavirus Pandemic in New York City.

Our orthopaedic surgery department at Montefiore Medical Center and Albert Einstein College of Medicine is located within the Bronx, a borough of New York City, and serves a densely populated urban community. Since the beginning of the novel coronavirus outbreak in New York City, the medical center was forced to rapidly adapt to the projected influx of critically ill patients. The aim of this report is to outline how our large academic orthopaedic surgery department adopted changes and alternative practices in response to the most daunting challenge to public health in our region in over a century. We hope that this report provides insight for others facing similar challenges.