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1.
Cell Mol Life Sci ; 79(6): 309, 2022 May 21.
Article in English | MEDLINE | ID: covidwho-1850296

ABSTRACT

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.


Subject(s)
Antimicrobial Cationic Peptides , COVID-19 , Thrombosis , Blood Coagulation Factors , COVID-19/complications , Fibrinogen , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombosis/virology
2.
Omega ; : 102683, 2022.
Article in English | ScienceDirect | ID: covidwho-1851899

ABSTRACT

The outbreak of extraordinary disruptive events, e.g., the COVID-19 pandemic, has greatly impacted the orderly operation in global supply chains (SCs), and may lead to the SC breakdown. Regulatory actions, such as government interventions during the pandemic, can greatly mitigate the disruption propagation (i.e., the ripple effect) and improve SC viability. However, existing works that focus on the disruption propagation management have not considered the possibility of such interventions. Motivated by the fact, in this study, we investigate a new disruption propagation management problem in a multi-echelon SC with limited intervention budget. The aim is to minimize disruption risk measured by the disrupted probability of target participants in the SC. For the problem, a novel approach, combining the Causal Bayesian Network (CBN), the do-calculus and the mathematical programming, is developed. Specially, two mixed-integer non-linear programming models are constructed to determine appropriate interventions. To enhance the proposed mathematical models, two valid inequalities are proposed. Then, a problem-specific genetic algorithm (GA) is developed for handling large-scale problem instances. Numerical experiments on a case study and randomly generated instances are conducted to evaluate the efficiency of the proposed models, the valid inequalities and the GA. Based on experiment analysis, managerial insights are drawn.

3.
J Clin Invest ; 132(10)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1846632

ABSTRACT

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Middle Aged , SARS-CoV-2 , T-Lymphocytes , Young Adult
4.
Biochemical and biophysical research communications ; 2022.
Article in English | EuropePMC | ID: covidwho-1843200

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a pandemic of acute respiratory disease, namely coronavirus disease 2019 (COVID-19). Currently, effective drugs for this disease are urgently warranted. Anisodamine is a traditional Chinese medicine that is predicted as a potential therapeutic drug for the treatment of COVID-19. Therefore, this study aimed to investigate its antiviral activity and crucial targets in SARS-CoV-2 infection. SARS-CoV-2 and anisodamine were co-cultured in Vero E6 cells, and the antiviral activity of anisodamine was assessed by immunofluorescence assay. The antiviral activity of anisodamine was further measured by pseudovirus entry assay in HEK293/hACE2 cells. Finally, the predictions of crucial targets of anisodamine on SARS-CoV-2 were analyzed by molecular docking studies. We discovered that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells, and reduced the SARS-CoV-2 pseudovirus entry to HEK293/hACE2 cells. Furthermore, molecular docking studies indicated that anisodamine may target SARS-CoV-2 main protease (Mpro) with the docking score of −6.63 kcal/mol and formed three H-bonds with Gly143, Cys145, and Cys44 amino acid residues at the predicted active site of Mpro. This study suggests that anisodamine is a potent antiviral agent for treating COVID-19. Graphical Image 1

5.
J Clin Lab Anal ; 36(6): e24491, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1826010

ABSTRACT

BACKGROUND: The rapid identification and isolation of individuals infected with SARS-CoV-2 are fundamental countermeasures for the efficient control of the COVID-19 pandemic, which has affected millions of people around the world. Real-time RT-PCR is one of the most commonly applied reference methods for virus detection, and the use of pooled testing has been proposed as an effective way to increase the throughput of routine diagnostic tests. However, the clinical applicability of different types of real-time RT-PCR tests in a given group size remains inconclusive due to inconsistent regional disease prevalence and test demands. METHODS: In this study, the performance of one dual-target conventional and two point-of-care real-time RT-PCR tests in a 5-specimen pooled testing strategy for the detection of SARS-COV-2 was evaluated. RESULTS: We demonstrated the proof of concept that all of these real-time RT-PCR tests could feasibly detect SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens that contain viral RNA loads in the range of 3.48 × 105 to 3.42 × 102 copies/ml through pooled testing in a group size of 5 with overall positive percent agreement (pooling vs. individual testing) ranging from 100% to 93.75%. Furthermore, the two POC real-time RT-PCR tests exhibited comparable sensitivity to that of the dual-target conventional one when clinical specimens were tested individually. CONCLUSION: Our findings support the feasibility of using real-time RT-PCR tests developed as a variety of platforms in routine laboratory detection of suspected COVID-19 cases through a pooled testing strategy that is beneficial to increasing the daily diagnostic capacity.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Pandemics , Point-of-Care Systems , Point-of-Care Testing , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity
6.
Transbound Emerg Dis ; 2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1774901

ABSTRACT

The ongoing enzootic circulation of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and North Africa is increasingly raising the concern about the possibility of its recombination with other human-adapted coronaviruses, particularly the pandemic SARS-CoV-2. We aim to provide an updated picture about ecological niches of MERS-CoV and associated socio-environmental drivers. Based on 356 confirmed MERS cases with animal contact reported to the WHO and 63 records of animal infections collected from the literature as of 30 May 2020, we assessed ecological niches of MERS-CoV using an ensemble model integrating three machine learning algorithms. With a high predictive accuracy (area under receiver operating characteristic curve = 91.66% in test data), the ensemble model estimated that ecologically suitable areas span over the Middle East, South Asia and the whole North Africa, much wider than the range of reported locally infected MERS cases and test-positive animal samples. Ecological suitability for MERS-CoV was significantly associated with high levels of bareland coverage (relative contribution = 30.06%), population density (7.28%), average temperature (6.48%) and camel density (6.20%). Future surveillance and intervention programs should target the high-risk populations and regions informed by updated quantitative analyses.

7.
BMC Med Educ ; 22(1): 154, 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1731527

ABSTRACT

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.


Subject(s)
COVID-19 , Students, Medical , COVID-19/epidemiology , Career Choice , Cross-Sectional Studies , Humans , Intention , Occupations , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
8.
Endocr Metab Immune Disord Drug Targets ; 21(12): 2213-2219, 2021.
Article in English | MEDLINE | ID: covidwho-1714871

ABSTRACT

AIMS: To investigate the influence of body mass index (BMI) on the association between psychological stress and physical fitness. BACKGROUND: Both obesity and psychological stress reduce exercise performance. OBJECTIVE: It is unknown whether obesity may modify the relationship. METHODS: A population of 4,080 military subjects in Taiwan was divided to three groups according to the BMI ≥27.0 kg/m2 (obesity), 24.0-26.9 kg/m2 (overweight) and 18.5-23.9 kg/m2 (normal weight). Normal, slight, and great psychological stress was evaluated by the Brief Symptoms Rating Scale (BSRS-5) score ≤5, 6-9, and ≥10, respectively. Aerobic and anaerobic fitness were respectively evaluated by time for a 3000-meter run and numbers of 2-minute sit-ups and 2-minute push-ups. Analysis of covariance (ANCOVA) with adjustments for age and sex was used to determine the relationship. RESULTS: The mean time (sec) for a 3000-meter run (standard error) under slight and great stress differed from that under normal stress in the normal weight (881.0 (11.0) and 877.9 (5.8) vs. 862.2 (1.7), p=0.089 and 0.0088, respectively) and in the obesity (928.1 (16.8) and 921.8 (10.7) vs. 895.2 (1.6), p=0.054 and 0.016, respectively), while the differences were not significant in the overweight (877.1 (12.7) and 877.5 (7.1) vs. 867.1 (2.1), both p >0.5). The impacts of the BMI on 2-minute sit-ups had a similar pattern with that on a 3000-meter run whereas the impact of the BMI on 2-minute push-ups was insignificant. CONCLUSIONS: Mental stress may not affect physical fitness in overweight military personnel. The mechanism is not clear and should be further investigated.


Subject(s)
Cardiorespiratory Fitness , Military Personnel , Body Mass Index , Hospitalization , Humans , Stress, Psychological/diagnosis , Stress, Psychological/epidemiology
9.
Vaccines (Basel) ; 10(2)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1708024

ABSTRACT

BACKGROUND: The ChAdOx1 nCoV-19 vaccine has been widely administered against SARS-CoV-2 infection; however, data regarding its immunogenicity, reactogenicity, and potential differences in responses among Asian populations remain scarce. METHODS: 270 participants without prior COVID-19 were enrolled to receive ChAdOx1 nCoV-19 vaccination with a prime-boost interval of 8-9 weeks. Their specific SARS-CoV-2 antibodies, neutralizing antibody titers (NT50), platelet counts, and D-dimer levels were analyzed before and after vaccination. RESULTS: The seroconversion rates of anti-RBD and anti-spike IgG at day 28 after a boost vaccination (BD28) were 100% and 95.19%, respectively. Anti-RBD and anti-spike IgG levels were highly correlated (r = 0.7891), which were 172.9 ± 170.4 and 179.3 ± 76.88 BAU/mL at BD28, respectively. The geometric mean concentrations (GMCs) of NT50 for all participants increased to 132.9 IU/mL (95% CI 120.0-147.1) at BD28 and were highly correlated with anti-RBD and anti-spike IgG levels (r = 0.8248 and 0.7474, respectively). Body weight index was statistically significantly associated with anti-RBD IgG levels (p = 0.035), while female recipients had higher anti-spike IgG levels (p = 0.038). The GMCs of NT50 declined with age (p = 0.0163) and were significantly different across age groups (159.7 IU/mL for 20-29 years, 99.4 IU/mL for ≥50 years, p = 0.0026). Injection-site pain, fever, and fatigue were the major reactogenicity, which were more pronounced after prime vaccination and in younger participants (<50 years). Platelet counts decreased and D-dimer levels increased after vaccination but were not clinically relevant. No serious adverse events or deaths were observed. CONCLUSION: The vaccine is well-tolerated and elicited robust humoral immunity against SARS-CoV-2 after standard prime-boost vaccination in Taiwanese recipients.

10.
Vaccines (Basel) ; 10(2)2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1707893

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) patients tend to have a reduced immune response to infection and vaccination. The efficacy of current available COVID-19 vaccines in CKD patients has not been widely evaluated. METHODS: In the present study, three hundred and eight chronic dialysis patients received ChAdOx1 nCoV-19 (Oxford-AstraZeneca, AZ). Blood tests using an antibody against the receptor-binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike protein had performed at four designed time points before and after the first and second vaccine. RESULTS: The mean age of patients was 65.5 ± 12.38 years, and the male/female ratio was 61.4%:38.6% (189/119). Two weeks after the first vaccination, only 37.66% of patients had a positive antibody response (>50 AU/mL). However, 65.58% of the participants showed a delayed antibody response ten weeks after the first vaccine. Four weeks after the second vaccine, 94.16% of participants had positive antibody levels. Age was the most significant factor associated with antibody response. Flow cytometry analysis revealed that immune-naïve patients had significantly lower early active B cells and proliferative B cells than the age- and sex-matched immune responders. CONCLUSION: Despite a delayed response, 94.16% of chronic dialysis patients achieved a positive antibody response after two doses of the AZ vaccine. Age is the most significant factor associated with antibody response.

11.
J Immunol Res ; 2022: 1433323, 2022.
Article in English | MEDLINE | ID: covidwho-1697599

ABSTRACT

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m6A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers.


Subject(s)
Atherosclerosis/genetics , Epigenesis, Genetic , Neoplasms/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Autoimmune Diseases/genetics , Datasets as Topic , Gene Expression Profiling , Humans , Inflammation/genetics , Metabolic Diseases/genetics , Methylation
12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323734

ABSTRACT

Background: :Undergraduate medical (UM) students faced the realities of the difficulties inherent in medical careers due to the coronavirus 2019 (COVID-19) outbreak. Thus imperative containment measures could affect UM students’ career intentions. There is limited information regarding the factors potentially associated with these students’ career change intentions.Methods:we conducted a cross-sectional survey to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students in August 2020. Univariate analyses and logistic regression analysis were used to identify the factors that contributed to any change of career intention. Results: A total of 2,040 medical students were contained from Hubei University of Medicine. The change of career intention was related to grade, attitude towards being a health worker and the impact of the COVID-19 pandemic. Conclusions: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19’s impact on the participants’ lives. Treating large-scale public health emergencies in rational way, setting up correct views of occupation choice and building reasonable career planning may reduce the loss of medical talents.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319516

ABSTRACT

Objective: Novel coronavirus (nCoV, SARS-CoV-2) infection becomes a world-wide epidemic which has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed. Methods: : The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23 rd , 2020 to February 20 th , 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study. Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea (a child patient of four years old), 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications with basic diseases: there were hypertension in 3 cases, diabetes in 2 cases, and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. There’s another one who had depression and suicidal tendency. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: the mild child patient (4 years old) was administrated with 2.75ml lopinavir / ritonavir oral liquid (twice per day) and intravenous drip of 0.17g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h for one week. Meanwhile, the child was asked to take azithromycin orally. 7 moderate patients were treated with intravenous drip of 0.5g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h (twice per day) and two pieces of lopinavir/ritonavior (twice per day) for 7-10 days. In the same time, patients were given with reasonable amount of antibiotics by oral or intravenous drip. 1 severe patient and 1 critical patent were treated with 5,000,000 U recombinant human interferon α2b injection (3,000,000 U/pc) and aerosol inhalation of 2ml sterile water for injection (5ml*50 pcs/ box), twice per day. Besides, they took 2 pieces of lopinavir/ritonavior, twice per day. The whole treatment program lasted for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. The critical patient was also provided with mechanical ventilation. During the treatment, severe and critical patients were treated by resochin for 4-5 days for evident respiratory symptoms. One moderate patient was treated with 2 pieces of lopinavir/ritonavior, twice per day. In the same time, it was administrated by intravenous drip of antibiotics. However, resochin treatment was applied for positive novel coronavirus nucleic acid of respiratory sputum specimen after 11 days of treatment. Discharge: After treatment, patients with body temperatures of all patients recovered to normal level, and respiratory symptoms and digestive tract symptoms relieved significantly, significant coefficient of exudative lesion at lung according to chest CT and negative novel coronavirus nucleic acid of continuous two respiratory sputum specimens (sampling interval was at least 1 day) were allowed to be discharged. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea. Conclusions: : SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction. If lopinavir/ritonavior administration and / or combined with ribavirin and RHI α2b is invalid, adding resochin might be effective.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315658

ABSTRACT

Since early 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly across the world. As at the date of writing this article, the disease has been globally reported in 223 countries and regions, infected over 108 million people and caused over 2.4 million deaths (https://covid19.who.int/, accessed on Feb. 17, 2021). Avoiding person-to-person transmission is an effective approach to control and prevent the pandemic. However, many daily activities, such as transporting goods in our daily life, inevitably involve person-to-person contact. Using an autonomous logistic vehicle to achieve contact-less goods transportation could alleviate this issue. For example, it can reduce the risk of virus transmission between the driver and customers. Moreover, many countries have imposed tough lockdown measures to reduce the virus transmission (e.g., retail, catering) during the pandemic, which causes inconveniences for human daily life. Autonomous vehicle can deliver the goods bought by humans, so that humans can get the goods without going out. These demands motivate us to develop an autonomous vehicle, named as Hercules, for contact-less goods transportation during the COVID-19 pandemic. The vehicle is evaluated through real-world delivering tasks under various traffic conditions.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314408

ABSTRACT

Motivation: The coronavirus disease 2019 (COVID-19) caused by a new type of coronavirus has been emerging from China and led to thousands of death globally since December 2019. Despite many groups have engaged in studying the newly emerged virus and searching for the treatment of COVID-19, the understanding of the COVID-19 target-ligand interactions represents a key chal-lenge. Herein, we introduce COVID-19 Docking Server, a web server that predicts the binding modes between COVID-19 targets and the ligands including small molecules, peptides and anti-bodies. Results: Structures of proteins involved in the virus life cycle were collected or constructed based on the homologs of coronavirus, and prepared ready for docking. The meta platform provides a free and interactive tool for the prediction of COVID-19 target-ligand interactions and following drug discovery for COVID-19.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308911

ABSTRACT

During its first month, the recently emerged 2019 Wuhan novel coronavirus (SARS-CoV-2) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of SARS-CoV-2 and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan .

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308199

ABSTRACT

Background: The COVID-19 pandemic has had a significant impact on orthopaedic trauma worldwide, but the extent of this impact regarding the low-risk period is still unclear. This study aims to evaluate the epidemiology of open limbs fractures during the different risk periods and the effect of routine prevention and control measures. Methods: A retrospective multi-centre cohort study was conducted in three different level trauma centres. Three 60-day periods were analyzed: the high-risk period - 2020/1/24-2020/3/24, the low-risk period - 2021/1/24-2021/3/25, and the no-risk period as a control group for comparison - 2019/1/24-2019/3/25. Demographic data, medical history, and surgery and antibiotic therapy data at presentation were collected and evaluated. Results: A total of 123 patients met the inclusion criteria. We observed a significant "J" shaped change in the total number of patients, with fewer patients in 2020 (n=34, -17%) and more in 2021 (n=48, +17%) compared to 2019 (n=41). However, fewer patients visited the level I centre in the low-risk period (82.9% 2019 vs. 70.6% 2020 vs. 56.3% 2021, P=0.024). Meanwhile, longer antibiotics therapy period (>48 hours) were more prevalent in low-risk period (39% 2019 vs. 58.8% 2020 vs. 68.8% 2021, P=0.018). Regarding definitive closure type, increase in direct closure was observed in high-risk period (51% 2019 vs. 78.9% 2020 vs. 63.5% 2021, P=0.024). Conclusion: During the high-risk period, the total number of patients was expected to decline, whereas in the low-risk period, the number may increase. They preferred the lower level II and III centre for patients during the pandemic rather than the higher level I centre. For surgeons, they were prone to direct closure and a more extended antibiotic therapy period. Routine prevention and control measures seem not adversely affect the treatment outcomes and process of open fractures. Trial registration ChiCTR, ChiCTR 2100046151. Registered 5 May 2021, http://www.chictr.org.cn/edit.aspx?pid=123490&htm=4.

18.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327774

ABSTRACT

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a "turning point". The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325434

ABSTRACT

Objective: To compare the epidemiological and clinical characteristics of confirmed and suspected corona virus disease 2019 (COVID-19) cases via the process of “triage-screening-isolation-transfer” in the hospitals of non-epidemic areas. Methods: : The general data, epidemiological history, clinical symptoms, laboratory examination, and chest computed tomography (CT) imaging characteristics of 38 patients with suspected COVID-19, admitted between January 21 and March 5, 2020, were analyzed. Results: : According to the results of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) ribonucleic acid (RNA) testing, the patients were divided into study group (RNA positive) and control group (RNA negative). Ultimately, 8 cases were RNA-positive and diagnosed as CDVID-19, and 30 cases were negative. Approximately half of the patients in the study group returned to Chongqing from Wuhan;this number was significantly larger than that of the control group (P<0.05). The number of subjects in close contact with the confirmed cases with SARS-CoV-2 RNA-positive and the incidence of aggregation was significantly larger in the study group than in the control group (both P<0.05). The clinical symptom of the study group was mainly low fever (with or without cough). The patients with decreased white blood cells (WBC) in the study group were significantly more than those in the control group (P<0.05). Both group had reduced lymphocytes (Lym) but the number of patients with increased C-reactive protein (CRP) in the study group was significantly more than that in the control group (P<0.05). There were different degrees of chest CT abnormalities in both study and control group (P > 0.05). Conclusion: The epidemiological investigations in screening for infectious diseases is crucial. The risk of infection was high from the primary epidemic area and/or in close contact with the confirmed case. The most common form of clustering occurrence was family aggregation. CDVID-19 was mainly characterized by fever and respiratory symptoms, although asymptomatic infection may also occur. Decreased WBC, decreased Lym, and increased CRP are common characteristics but can also be combined with other respiratory tract virus infections. COVID 19 screening by chest CT alone had certain limitations in non- epidemic areas.

20.
Front Microbiol ; 12: 820698, 2021.
Article in English | MEDLINE | ID: covidwho-1686502

ABSTRACT

Rapid and sensitive nucleic acid detection of SARS-CoV-2 has contributed to the clinical diagnosis and control of COVID-19. Although detection of virus genomic RNA (gRNA) has been commonly used in clinical diagnosis, SARS-CoV-2 gRNA detection could not discriminate between active infectious virus with remnant viral RNA. In contrast to genomic RNA, subgenomic RNAs (sgRNAs) are only produced when the virus is actively replicating and transcription, detection of sgRNA could be an indication to evaluate infectivity. CRISPR/Cas-based nucleic acid detection methods have been considered potential diagnostic tools due to their intrinsic sensitivity, specificity and simplicity. In this study, to specifically detect active virus replication, we developed a CRISPR-based active SARS-CoV-2 (CRISPR-actCoV) detection strategy by detecting sgRNAs of SARS-CoV-2. CRISPR-actCoV with CRISPR Cas12a-assisted fluorescence reporter system enables detection of sgRNAs at 10 copies in 35 min with high specificity and can be read out with naked eyes. Further, we performed CRISPR-actCoV mediated sgRNA detection in 30 SARS-CoV-2 potentially infected clinical samples, and 21 samples were SARS-CoV-2 sgRNA positive. A quantitative RT-PCR assay was also performed to detect gRNA of SARS-CoV-2 in parallel. Among the 30 clinical samples, 27 samples were gRNA positive. Taken together, CRISPR-actCoV provides an alternative for rapid and accurate detection of active SARS-CoV-2 and has great significance in better response of coronavirus causing epidemic disease.

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