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Throughout human history, deadly infectious diseases emerged occasionally. Even with the present-day advanced healthcare systems, the COVID-19 has caused more than six million deaths worldwide (as of 27 July 2022). Currently, researchers are working to develop tools for better and effective management of the pandemic. "Contact tracing " is one such tool to monitor and control the spread of the disease. However, manual contact tracing is labor-intensive and time-consuming. Therefore, manually tracking all potentially infected individuals is a great challenge, especially for an infectious disease like COVID-19. To date, many digital contact tracing applications were developed and used globally to restrain the spread of COVID-19. In this work, we perform a detailed review of the current digital contact tracing technologies. We mention some of their key limitations and propose a fully integrated system for contact tracing of infectious diseases using COVID-19 as a case study. Our system has four main modules-1) case maps;2) exposure detection;3) screening;and 4) health indicators that take multiple inputs like users' self-reported information, measurement of physiological parameters, and information of the confirmed cases from the public health, and keeps a record of contact histories using Bluetooth technology. The system can potentially evaluate the users' risk of getting infected and generate notifications to alert them about the exposure events, risk of infection, or abnormal health indicators. The system further integrates the Web-based information on confirmed COVID-19 cases and screening tools, which potentially increases the adoption rate of the system.
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Objective To evaluate the specificity of three consecutive batches of 2019-nCoV nucleic acid detection kit (fluorescence PCR) manufactured by Shanghai GeneoDx Biotech Co., LTD. Methods A total of 55 common respiratory pathogens, including endemic human coronaviruses (HKU1, OC43, NL63 and 229E), severe acute respiratory syndrome conronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS), seasonal influenza virus, rhinovirus, adenovirus, Klebsiella pneumonia and Mycobacterium tuberculosis, were grouped and used for verification of cross reactivity of the detection kit. According to the requirements in the Key Points of Technical Review for Registration of 2019 New Coronavirus Nucleic Acid Detection Reagents issued by Center for Medical Device Evaluation, National Medical Products Administration (NMPA), human mucoprotein, human blood, phenylephrine, oxymetazoline, sodium chloride (including those as preservatives) and other 29 interfering substances were selected to verify the anti-interference substances of this kit. Results In the verification for cross reactivity, the test results of mixed positive samples by the three consecutive batches of kit were positive, while those of negative samples were negative, indicating a coincidence rate of accuracy of 100%. The cross-reactive substances showed no effect on the test result by the kit. All the test results of positive and borderline positive samples were positive, while those of negative samples were negative, indicating a coincidence rate of accuracy of 100%. All the 29 kinds of endogenous / exogenous interfering substances showed no influence on the test results by this kit. Conclusion Hie new coronavirus 2019-nCoV nucleic acid detection kit (fluorescence PCR method) manufactured by Shanghai GeneoDx Biotech Co., LTD. showed no cross-reactivity with 55 common respiratory pathogens, while showed anti-interference properties against endogenous and exogenous interfering substances such as host tissue, common respiratory pathogen and common drugs for respiratory diseases in clinic. The specificity test result of the kit met the requirements for registration of 2019 new coronavirus nucleic acid detection reagents. The test results of three consecutive batches of kits were highly stable. Copyright © 2021 Changchun Institute of Biological Products. All rights reserved.
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Objective: The mechanism of action, metabolic kinetics, efficacy, safety and drug-drug interaction of molnupiravir were reviewed to provide a basis for clinical use. Method(s): Literature related to molnupiravir was systematically searched in Chinese Clinical Trial Registry, clinicaltrials.gov, Pubmed, Chinese Journal Full-text Database (CNKI) and Wanfang database, and the relevant information was reviewed. Results & Conclusion(s): Molnupiravir was the world's first small-molecule oral drug for COVID-19, which had been approved or authorized for emergency use in more than 40 countries all over the world. Molnupiravir was a ribonucleoside analogue that could be caused mutations in RNA products by viral RNA polymerase, and thus halt viral replication. Clinical trial results showed that molnupiravir could be reduced hospitalization and mortality rates in patients with mild and moderate COVID-19, and might be effective against SARS-CoV-2 mutant strains.Molnupiravir had good safety and tolerability, to provide reference for the treatment of COVID-19 in the future. Copyright © 2022, Chinese Journal of New Drugs Co. Ltd. All right reserved.
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Messenger ribonucleic acid (mRNA) vaccine is characteristic of subunit vaccines and live attenuated vectors. It can simultaneously induce humoral and cellular immunity, and has the advantage of easy to produce on a large scale. Therefore, great application prospects are seen in the field of infectious diseases and the treatment of major diseases. In the field of biomedicine, mRNA vaccine has been deeply cultivated for decades. With the outbreak of the COVID-19 epidemic and the pandemic, the process of listing mRNA vaccines has been greatly accelerated and promoted. The COVID-19 mRNA vaccines, with lipid nanoparticles (LNPs) as the carrier which deliver the mRNA encoding the COVID-19 spike protein antigen information to host cells, were successfully launched, showing good safety and efficacy. Meanwhile, the development of the delivery system, as the key technology of mRNA vaccines, has also become a "battlefield" for the development of mRNA technology. Various delivery technologies, including LNPs, are being actively developed in China and abroad. Safe and effective delivery with independent intellectual property rights will become the key to promote the marketing of mRNA products, which will obtain benefits in the future. This article reviews the mRNA vaccine delivery system and research progress. Copyright © 2022, Chinese Journal of New Drugs Co. Ltd. All right reserved.
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Objective To evaluate the specificity of three consecutive batches of 2019-nCoV nucleic acid detection kit (fluorescence PCR) manufactured by Shanghai GeneoDx Biotech Co., LTD. Methods A total of 55 common respiratory pathogens, including endemic human coronaviruses (HKU1, OC43, NL63 and 229E), severe acute respiratory syndrome conronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS), seasonal influenza virus, rhinovirus, adenovirus, Klebsiella pneumonia and Mycobacterium tuberculosis, were grouped and used for verification of cross reactivity of the detection kit. According to the requirements in the Key Points of Technical Review for Registration of 2019 New Coronavirus Nucleic Acid Detection Reagents issued by Center for Medical Device Evaluation, National Medical Products Administration (NMPA), human mucoprotein, human blood, phenylephrine, oxymetazoline, sodium chloride (including those as preservatives) and other 29 interfering substances were selected to verify the anti-interference substances of this kit. Results In the verification for cross reactivity, the test results of mixed positive samples by the three consecutive batches of kit were positive, while those of negative samples were negative, indicating a coincidence rate of accuracy of 100%. The cross-reactive substances showed no effect on the test result by the kit. All the test results of positive and borderline positive samples were positive, while those of negative samples were negative, indicating a coincidence rate of accuracy of 100%. All the 29 kinds of endogenous / exogenous interfering substances showed no influence on the test results by this kit. Conclusion Hie new coronavirus 2019-nCoV nucleic acid detection kit (fluo¬rescence PCR method) manufactured by Shanghai GeneoDx Biotech Co., LTD. showed no cross-reactivity with 55 common respiratory pathogens, while showed anti-interference properties against endogenous and exogenous interfering substances such as host tissue, common respiratory pathogen and common drugs for respiratory diseases in clinic. The specificity test result of the kit met the requirements for registration of 2019 new coronavirus nucleic acid detection reagents. The test results of three consecutive batches of kits were highly stable.
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Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro;also known as 3CL(pro)) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anticoronavirus agents. We solved the crystal structures of the main protease of SARSCoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.
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As of May 2021, 6 new vaccines against coronavirus disease 2019 (COVID-19) have been conditionally approved and urgently used in China, including products of 4 new inactivated vaccines, 1 new adenovirus vaccine and 1 new recombinant vaccine. All the six vaccine products have been under different stages of clinical trials in global scale, and the results of the clinical trials have demonstrated the safety of the vaccines and the efficacy against COVID-19. Focusing on the above products, this paper deeply summarizes the characteristics of different new vaccine products and the clinical trial results as the key evidence supporting the approval of the products. In addition, facing the current severe situation of COVID-19, the status and challenges regarding the research and development of new vaccines and therapeutics are analyzed. © 2022, Chinese Journal of New Drugs Co. Ltd. All right reserved.
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Under the pressures of the current global pandemic, researchers have been working hard to find a reliable way to suppress infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent the spread of COVID-19. Studies have shown that the recognition and binding of human angiotensin-converting enzyme 2 by the receptor-binding domain (RBD) of the spike protein on the surface of SARS-CoV-2 is a crucial step in viral invasion of human receptor cells, and blocking this process could inhibit the virus from invading normal human cells. Plasma treatment can disrupt the structure of the RBD and effectively block the binding process. However, the mechanism by which plasma blocks recognition and binding is not clear. In this study, the reaction between reactive oxygen species (ROS) in plasma and a molecular model of the RBD was simulated using a reactive molecular dynamics method. The results showed that the destruction of the RBD by ROS was triggered by hydrogen ion reactions: O and OH ed H atoms from the RBD, while the H atoms of H2O2 and HO2 were ed by the RBD. This hydrogen ion resulted in the breakage of C-H, N-H, O-H and C=O bonds and the formation of C=C and C=N bonds. The addition reaction of OH increased the number of O-H bonds and caused the formation of C-O, N-O and O-H bonds. The dissociation of N-H bonds led to the destruction of the original peptide bond structure and amino acid residues, changed the type of amino acid residues and caused the conversion of N-C and N=C and C=O and C-O. The simulation partially elucidated the microscopic mechanism of the interaction between ROS in plasma and the capsid protein of SARS-CoV-2, providing theoretical support for the control of SARS-CoV-2 infection by plasma, a contribution to overcoming the global pandemic.
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Corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global pandemic, and it is urgent to prevent and control the epidemic. It is recorded in history that the incense, pillow incense, and perfume made from aromatic drugs can be used to prevent diseases and exorcise evil spirits. Nowadays, people often use traditional Chinese medicine (TCM) to disinfect indoors to prevent the spread of colds and epidemics. In the process of preventing and treating COVID-19 pneumonia patients, comprehensive treatment of TCM has played an important role. At present, the epidemic situation of COVID-19 in China has been controlled in stages. More than 90% confirmed cases have been treated with TCM intervention. According to the actual situation of patients, TCM treatment strategies such as moistening dryness and storing fluid, dispelling heat and detoxification, aroma penetrating filth and releasing lung and reducing turbidity are given. The application of aromatic Chinese materia medica in COVID-19 is reviewed in this paper, in order to provide reference for prevention and treatment of later COVID-19 and other diseases and relative basic research.
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Objective: To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use. Methods: Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods. Results: By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively. Conclusion: The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.
Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination , Vaccines/adverse effects , Vaccines, InactivatedABSTRACT
More than 220 million Chinese children and adolescents are confined to their homes because of the corona virus disease 2019 (COVID-19) outbreak. Thanks to the strong administrative system in China, the emergency home schooling plan has been rigorously implemented. Although these measures and efforts are highly commendable and necessary, there are reasons to be concerned because prolonged school closure and home confinement during a disease outbreak might have negative effects on children's physical and mental health. It is the responsibility and keen interests of all stakeholders, from governments to parents, to ensure that the physical and mental impacts of the COVID-19 epidemic on children and adolescents are kept minimal. Copyright © 2020, Editorial Department of Journal of Shanghai Second Medical University. All right reserved.
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Objective: Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province. Methods: The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared. Results: A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M (P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant (P=0.003). Conclusion: COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.
Subject(s)
Coronavirus Infections/epidemiology , Epidemics , Pneumonia, Viral/epidemiology , COVID-19 , China/epidemiology , Cluster Analysis , Humans , PandemicsABSTRACT
Objective: To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods: We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results: Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1 049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days (P(25), P(75): 18, 31 days) and the median length of hospitalization were 20 days (P(25), P(75): 15,27 days). For severe cases, the median time of showing severe manifestations was on the 12(th) day after onset (P(25), P(75): 9(th) to 15(th) days), and the median time of severe manifestation lasted for 8 days (P(25), P(75): 4, 14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (aHR=1.87, 95%CI: 1.43-2.46), older age (aHR=1.67, 95%CI: 1.51-1.85), seeking medical care on day 2-3 after onset (aHR=1.73, 95%CI: 1.20-2.50) pre-existing diabetes (aHR=1.75, 95%CI: 1.12-2.73) and hypertension (aHR=1.49, 95%CI: 1.06-2.09). Conclusions: The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.