Multiplex and Ultrasensitive Detection of Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza A/B Nucleocapsid Proteins Based on Nanometer-Sized Core-Shell Superparamagnetic Antifouling Probes

Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A (Flu A), and influenza B (Flu B) show similar clinical symptoms, such as cough, fever, and dyspnea, but patients infected by these viruses should be treated differently. The rapid and accurate diagnosis of infections caused by SARS-CoV-2, Flu A or Flu B is critical during the influenza season. Herein, we synthesized core-shell magnetic particles (MNPs) with excellent antifouling properties and applied them in the MNP-based immunochromatographic test (MICT) for simultaneous detection of SARS-CoV-2, Flu A, and Flu B nucleocapsid(N) proteins in 20 min. Two kinds of carboxyl -modified MNPs, MNP@pMBAA and MNP@Si-SA, were prepared and evaluated as probes in the MICT. Among them, the MNP@ pMBAA showed lower nonspecific adsorption of proteins and low background noise in the application in MICTs. Particularly, the MNP@pMBAA50 bead-based MICT strip exhibited the highest signal-to-noise ratio for SARS-CoV-2 N protein detection with a limit of detection (LOD) of 0.072 ng/mL. Moreover, the proposed MICT strip demonstrated a minimal cross-reactivity and a broad linear dynamic detection range under a magnetic assay reader in the simultaneous detection of SARS-CoV-2, Flu A, and Flu B N proteins with relative LOD values of 0.0086, 0.012, and 0.018 ng/mL, respectively. The results demonstrated that the synthesized MNPs showed great potential for use as MICT probes for sensitive and multiplex detection of biomarkers in the development of point-of-care testing systems.

Multiplex and Ultrasensitive Detection of Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza A/B Nucleocapsid Proteins Based on Nanometer-Sized Core-Shell Superparamagnetic Antifouling Probes

Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A (Flu A), and influenza B (Flu B) show similar clinical symptoms, such as cough, fever, and dyspnea, but patients infected by these viruses should be treated differently. The rapid and accurate diagnosis of infections caused by SARS-CoV-2, Flu A or Flu B is critical during the influenza season. Herein, we synthesized core-shell magnetic particles (MNPs) with excellent antifouling properties and applied them in the MNP-based immunochromatographic test (MICT) for simultaneous detection of SARS-CoV-2, Flu A, and Flu B nucleocapsid(N) proteins in 20 min. Two kinds of carboxyl-modified MNPs, MNP@pMBAA and MNP@Si-SA, were prepared and evaluated as probes in the MICT. Among them, the MNP@pMBAA showed lower nonspecific adsorption of proteins and low background noise in the application in MICTs. Particularly, the MNP@pMBAA50 bead-based MICT strip exhibited the highest signal-to-noise ratio for SARS-CoV-2 N protein detection with a limit of detection (LOD) of 0.072 ng/mL. Moreover, the proposed MICT strip demonstrated a minimal cross-reactivity and a broad linear dynamic detection range under a magnetic assay reader in the simultaneous detection of SARS-CoV-2, Flu A, and Flu B N proteins with relative LOD values of 0.0086, 0.012, and 0.018 ng/mL, respectively. The results demonstrated that the synthesized MNPs showed great potential for use as MICT probes for sensitive and multiplex detection of biomarkers in the development of point-of-care testing systems. © 2023 American Chemical Society.

Research progress on clinical application of convalescent plasma from COVID-19 patients.

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients.Copyright © 2021 Chinese Medical Association

Research progress on clinical application of convalescent plasma from COVID-19 patients.

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients.Copyright © 2021 Chinese Medical Association

Research progress on clinical application of convalescent plasma from COVID-19 patients.

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients.Copyright © 2021 Chinese Medical Association

The Value of Internal Control during a Crisis: Evidence from Enterprise Resilience

Internal control is an important internal governance mechanism of enterprises and plays an important role in preventing and controlling corporate risks. This paper utilizes COVID-19 shocks and uses data from listed companies in China for 2019–2021 in order to study the impact of internal control on enterprise resilience and its functioning mechanism. The findings show that internal control significantly improves enterprise resilience during a crisis. By using firm characteristic quantile regressions, it is found that under a crisis, larger firms with sufficient cash flow from operating activities are more protected by internal control and more resilient. Mechanistic analysis suggests that internal control further increases enterprise resilience by improving resource allocation efficiency, reducing operating risk, and increasing innovation output. Further analysis shows that government support can enhance the resilience of firms during crises through tax and fiscal policies;a better business environment enhances firms' ability to withstand risks in crisis situations and helps them gain a competitive advantage in crisis situations. Based on this, this paper provides empirical evidence for revising and improving the internal control system of enterprises to reduce the negative impact of public health emergencies in the context of epidemics. © 2022 by the authors.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world. © 2022 The Authors

RNAi Degrades the SARS-CoV-2 Spike Protein RNA for Developing Drugs to Treat COVID-19

COVID-19 is caused by severe acute respiratory SARS-CoV-2. Regardless of the availability of treatment strategies for COVID-19, effective therapy will remain essential. A promising approach to tackle the SARS-CoV-2 could be small interfering (si) RNAs. Here we designed the small hairpin RNA (named as shRNA688) for targeting the prepared 813 bp Est of the S protein genes (Delta). The conserved and mutated regions of the S protein genes from the genomes of the SARS-CoV-2 variants in the public database were analyzed. A 813 bp fragment encoding the most part of the RBD and partial downstream RBD of the S protein was cloned into the upstream red florescent protein gene (RFP) as a fusing gene in the pCMV-S-Protein RBD-Est-RFP plasmid for expressing a potential target for RNAi. The double stranded of the DNA encoding for shRNA688 was constructed in the downstream human H1 promoter of the plasmid in which CMV promoter drives enhanced green fluorescent protein (EGFP) marker gene expression. These two kinds of the constructed plasmids were co-transfected into HEK293T via Lipofectamine 2000. The degradation of the transcripts of the SARS-CoV-2 S protein fusing gene expressed in the transfected HEK293T treated by RNAi was analyzed by RT-qPCR with a specific probe of the targeted SARS-CoV-2 S protein gene transcripts. Our results showed that shRNA688 targeting the conserved region of the S protein genes could effectively reduce the transcripts of the S protein genes. This study provides a cell model and technical support for the research and development of the broad-spectrum small nucleic acid RNAi drugs against SARS-CoV-2 or the RNAi drugs for the other hazard viruses which cause human diseases. Copyright © Weiwei Zhang, Linjia Huang, Jumei Huang, Xin Jiang, Xiaohong Ren, Xiaojie Shi, Ling Ye, Shuhui Bian, Jianhe Sun, Yufeng Gao, Zehua Hu, Lintin Guo, Suyan Chen, Jiahao Xu, Jie Wu, Jiwen Zhang, Daxiang Cui, and Fangping Dai.

An Effective Method for Privacy Concerns on Digital Contact Tracing Protocols

In the post-epidemic era of normalized COVID-19, digital contact tracing will continue to be used as an efficient epidemiological investigation tool. Meanwhile, its widespread use has raised concerns about long-term data privacy and security. In this paper, an effective method for privacy concerns on digital contact tracing protocols (DCTP) is proposed. Digital contact tracing protocols are classified from both technical and architectural perspective. Then, the LINDDUN (each letter of "LINDDUN"stands for a privacy threat type) privacy threat modeling framework is used to analyze the privacy threats that may be contained in different protocols. Last, mitigation strategies are provided to advance privacy protection for future digital contact tracing protocols. The experiment show that the proposed method significantly outperforms existing methods. © 2022 IEEE.

How will the COVID-19 Pandemic Affect the Asian Games? A Joint Analysis of Olympic and Pandemic Big Data

The outbreak of the COVID-19 pandemic has seriously affected the development schedule of international sports. The postponement of the Asian Games has brought more concerns to the development of Asian competitive sport. Still, there is no quantitative conclusion on the impact of the pandemic on the Asian Games as a whole. Regarding this, we use big data technology to analyze the Tokyo Olympics and the COVID-19 pandemic data to explore the impact of the pandemic on the development of Asian competitive sport and large-scale comprehensive sports events. Our results suggest that the medal share of each country is significantly correlated with the pandemic. © 2022 IEEE.

A Cardboard-Based Virtual Reality Study on Self-Avatar Appearance and Breathing

Cardboard-based virtual reality is an affordable solution for experiencing virtual reality content. Particularly during the COVID-19 pandemic, several studies used cardboard-based virtual reality remotely to minimize viral spread. We conducted a study to explore the potentials of low-cost virtual reality on participants' sense of presence and body ownership illusion in our research lab, thereby providing a controlled research setting. Our 2 (Avatar: realistic vs. mannequin self-avatar) x 2 (Breathing;breathing vs. no breathing motion) study investigated presence and body ownership when participants were instructed to observe a virtual environment passively through a cardboard-based virtual reality application while being embodied as a self-avatar. Our study's results indicated that: (1) the mannequin self-avatar exerted a stronger effect on participants' presence;(2) younger participants who experienced the mannequin avatar reported stronger body ownership compared with older participants;and (3) while experiencing a mannequin avatar with no breathing motion, participants with prior VR experience reported higher body ownership illusion compared with participants with no prior VR experience. In this paper, we discuss our findings, as well as the study's limitations and future research directions.

Privacy Analysis and Comparison of Pandemic Contact Tracing Apps

During the period of epidemic prevention and control, contact tracing systems are developed in many countries, to stop or slow down the progression of COVID-19 contamination. However, the privacy issues involved in the use of contact tracing apps have also attracted people's attention. First, we divide contact tracing techniques into two types: Bluetooth Low Energy (BLE) based and Global Positioning System (GPS) based techniques. In order to clear understand the system structure and its elements, we create data flow diagram (DFD) of each types. Second, we analyze the possible privacy threats contained in various types of contact tracing apps by applying LINDDUN, which is a threat modeling technique for personal information protection. Third, we make a comparison and analysis of various contact tracing techniques from privacy point of view. These studies can facilitate improve tracing and security performance to contact tracing apps through comparisons between different types.

Development of Exhaled Breath Diagnosis Sensors for Rapid Identification of COVID-19 Patients

The novel coronavirus pneumonia, a global pandemic disease named as coronavirus disease 2019, has caused enormous losses on the health and economies of people all over the world, while there is still a lack of quick and sensitive diagnostic method and effective therapy. Developing rapid diagnostic method for coronavirus disease 2019 has become exceptional urgent. Herein we report a rapid diagnostic method for the novel coronavirus through monitoring the volatile biomarkers in human exhaled breath. The breath volatile biomarkers are derived from the metabolism of novel coronavirus, including acetoin, 2,4,6-trimethylpyridine, 3-methyl tridecane, tetradecane, isooctyl alcohol, pentadecane, hexadecane, 1-methylene-1H-indene. By comparing the types and concentrations of the volatile biomarkers in human exhaled breath combined with SERS sensor, we could distinguish between the healthy person and the patients with coronavirus disease 2019. This work confirms that various volatile organic compounds metabolized by novel coronavirus can be employed for rapidly screening of patients with coronavirus disease 2019, and has broad application prospects in the prevention and control of the epidemic.

Impact on China's CO2 emissions from COVID-19 pandemic

Assessing the impact of the COVID-19 pandemic on China's carbon emissions is crucial for China to lead global climate change mitigation. However, thorough quantitative analyses of the pandemic's effects on energy use and emissions are still lacking. This is largely because well-known published datasets of greenhouse gas emissions are based on annual statistics that commonly become available one or more years after they are gathered. A high temporal resolution emission dataset is critical to capture the immediate effects of an event such as the COVID-19 pandemic. Such an improved resolution might also allow policy makers to more quickly observe the effects of policies aimed at decreasing CO2 emissions, facilitating rapid adjustments. Here, based on a newly developed, near real-time global emission dataset, Carbon Monitor, we estimate China's daily energy consumption and associated CO2 emissions and use this dataset to estimate the impact of COVID-19 on CO2 emission trends. Such a near-real-time CO2 emission database based on activity data quantifies both anthropogenic CO2 emissions from fossil fuel combustion and cement production. We show that the higher-resolution emission dataset can be used to assess the impact of COVID-19 (and similar future disruptions) within a reasonable range of uncertainty. This study finds that China's CO2 emissions in the first four months of 2020 decreased by 6.9% compared to the same period in 2019, with a total emission reduction of 234.5 million tons of CO2. The provinces of Jiangsu, Hubei, and Zhejiang were most severely affected by COVID-19, accounting for 19.4%, 17.0% and 12.5% of the total reduction in CO2 emissions, respectively. The reduction of CO2 emissions from Shandong, Hebei, Anhui, Henan and Chongqing provinces is more than 10 Mt CO2, and the sum of the reduction from these five provinces accounts for 28.8% of the national total reductions. CO2 emissions in Yunnan Province, Gansu Province, Guangxi Zhuang Autonomous Region, Ningxia Hui Autonomous Region, Shaanxi Province and Xinjiang Uygur Autonomous Region increased slightly compared to the same period in 2019. In addition, COVID-19 has a little effect on CO2 emissions from Qinghai Province and Tibet Autonomous Region. This decrease in atmospheric pollutants is the largest decrease recorded and is consistent with the decrease in air pollutants observed by ground observation stations. This study finds that China's national economy has recovered rapidly. In April 2020, China's carbon emissions returned to the same level observed last year. This study predicts that China's full-year CO2 in 2020 will be 2% lower than in 2019. This will be the first time China has experienced a decline since 1997. China's carbon emissions have not rebound significantly, and the dynamic changes in China's CO2 indicate a rapid recovery of the Chinese economy. Regarding long-term trends, it is still unclear how much China's CO2 emissions will change at the end of this year and how fast the economy and industry will return to normal. With policy support, the economy will be stimulated as the pandemic fades. The IMF predicts that the global annual economic output will decrease sharply by -3.0% in 2020, which is worse than the financial crisis in 2008, based on the assumption that COVID-19 will fade globally in the second half of this year. Based on current emission dynamics, China's emission decline is estimated to be less than 5%, and the future trend will be affected by whether there will be another pandemic in the future. Current statistics are still not capable of comprehensively capturing the dynamics of CO2 emissions during the COVID-19 pandemic, and further monitoring, observation and data collection are urgently needed. © 2021, Science Press. All right reserved.

Research progress on clinical application of convalescent plasma from COVID-19 patients

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients. © 2021 Chinese Medical Association

Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta.

OBJECTIVES: To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta. METHODS: Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). RESULTS: Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae. CONCLUSIONS: ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

A magnetic nanoparticle labeled immunochromatography kit for sars-cov-2 infection diagnosis

The novel coronavirus disease (COVID-19) is breaking out and spreading rapidly around the world. There is an urgent need for an accurate and rapid detection method to quickly find infected patients and asymptomatic carriers in order to prevent the spread of the severe acute respiratory syndrome coronavirus [SARS-CoV-2]. In this paper, we designed a test strip which used the principle of double antigen sandwich. Fe3O4 magnetic nanobeads are firstly coupled with specific antibodies, and the S protein of the new coronavirus is used as the coating antigen to capture specific antibodies against the new coronavirus, which is used to detect the virus nucleoprotein of specific antibodies in clinical samples. At the same time, Fe3O4 magnetic nanobeads have unique magnetic properties, which can be used to generate different types of detection signals and simplify the detection process. These results can be judged by color changes and magnetic changes at the test and control lines. Compared with the traditional method, this test strip of Fe3O4 magnetic nanobeads has high sensitivity and can qualitatively detect samples within 15 minutes. The magnetic performance of the magnetic nanobeads can be used to improve the sensitivity of the strip in our further research and product development.

Designing a novel nano-vaccine against SARS-CoV-2

The new coronavirus SARS-CoV-2 has become a global pandemic, which has had a huge impact on the lives of people around the world and has caused huge impacts and losses on global economic development. To now, there is still no effective drug or therapy against coronavirus. A large number of studies have shown that vaccines are the ultimate weapon to eliminate major infectious diseases. The development of new vaccines against new coronaviruses is the best way to prevent new coronavirus infections. In this study, we developed a new vaccine against the new coronavirus by combining our self-developed nano adjuvant loaded with carnosine graphene oxide adjuvant with loaded with CpG molecule and RBD protein antigen. Our results showed that this vaccine can produce high titer anti-SARS-CoV-2 RBD antibody neutralizing SARS-CoV-2 in mice within 2 weeks.

Development of SARS-CoV-2 isothermal amplification detection kits

The SARS-CoV-2 isothermal amplification detection kits based on loop-mediated isothermal amplification (LAMP) were developed and evaluated on three types samples of SARS-CoV-2. The kits included enzyme reaction mixtures and chromogenic agents. After the isothermal amplification reactions were completed, the reaction results were judged by using the chromogenic agents to determine whether SARS-CoV-2 exists in the samples to be tested. The detection kits have the advantages of convenient operation, fast detection speed and high sensitivity up to 1 copy of virus particles per reaction, which can speed up the detection speed of suspected cases, and avoid the missing detection problems caused by the low detection sensitivity.