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1.
Microorganisms ; 11(2)2023 Feb 06.
Article in English | MEDLINE | ID: covidwho-2268787

ABSTRACT

When piglets are infected by virulent and avirulent strains of swine acute diarrhea syndrome coronavirus (SADS-CoV), there are obvious differences in their clinical symptoms; however, the specific mechanisms of pathogenicity and the immune regulation of highly pathogenic and low pathogenic strains are unknown. We collected intestinal tissues from SADS-CoV-infected piglets, performed a whole transcriptome sequencing analysis, including mRNA, miRNA, lncRNA, cicrRNA, and TUCP, and performed functional and correlation analyses of differentially expressed RNAs. Our results showed that the differentially expressed RNAs in group A versus group B (AvsB), group A versus group C (AvsC), and group B versus group C (BvsC) were relevant to immune and disease-related signaling pathways that participate in the organisms' viral infection and immune regulation. Furthermore, data obtained from the HAllA analysis suggested that there was a strong correlation between the differentially expressed RNAs. Specifically, LNC_011487 in the P set was significantly negatively correlated with ssc-miR-215, and LNC_011487 was positively correlated with PI3. Moreover, we also constructed a differentially expressed RNA association network map. This study provides a valuable resource for studying the SADS-CoV transcriptome and pathogenic mechanism from the perspective of RNA to understand the differences in and consistency of the interaction between virulent and attenuated SADS-CoV strains and hosts.

2.
Front Microbiol ; 14: 1126707, 2023.
Article in English | MEDLINE | ID: covidwho-2264667

ABSTRACT

In this study, we detected a circular replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA virus [named Po-Circo-like (PCL) virus] in intestinal tissue and fecal samples of pigs. PCL virus contains a single-stranded DNA genome, and ORF1 encodes the Rep and not the typical capsid protein encoded in PCV. The Rep protein may be responsible for viral genome replication. In addition, PCL virus may be one of the pathogens causing diarrhea symptoms in pigs. We identified four strains of PCL virus in two different pig farms with severe diarrhea outbreaks in Hunan Province, China. The strains in this study share 85.7-99.7% nucleic acid identity and 84.7-100% amino acid identity with Rep of the reference strains. A multiple sequence alignment of these PCL viruses and Bo-Circo-like CH showed a identity of 93.2% for the Rep protein, and the nucleotide identity was 86.7-89.3%. Moreover, Bo-Circo-like CH and HN75, HN39-01, HN39-02 had similar stem-loop sequences. In conclusion, the present study is the first detailed report of the PCL virus in Hunan provinces, which is a potential new virus in pigs that might be involved in cross-species transmission. Further investigation is needed to determine the pathogenesis of this virus and its epidemiologic impact.

3.
Allergy ; 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2237479

ABSTRACT

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

4.
Applied Microbiology ; 2(4):837-854, 2022.
Article in English | MDPI | ID: covidwho-2089990

ABSTRACT

Mucosal vaccination offer an advantage over systemic inoculation from the immunological viewpoint. The development of an efficient vaccine is now a priority for emerging diseases such as COVID-19, that was declared a pandemic in 2020 and caused millions of deaths globally. Lactic acid bacteria (LAB) especially Lactobacillus are the vital microbiota of the gut, which is observed as having valuable effects on animals' and human health. LAB produce lactic acid as the major by-product of carbohydrate degradation and play a significant role in innate immunity enhancement. LAB have significant characteristics to mimic pathogen infections and intrinsically possess adjuvant properties to enhance mucosal immunity. Increasing demand and deliberations are being substantially focused on probiotic organisms that can enhance mucosal immunity against viral diseases. LAB can also strengthen their host's antiviral defense system by producing antiviral peptides, and releasing metabolites that prevent viral infections and adhesion to mucosal surfaces. From the perspectives of 'one health';and the use of probiotics, conventional belief has opened up a new horizon on the use of LAB as antivirals. The major interest of this review is to depict the beneficial use of LAB as antivirals and mucosal immunity enhancers against viral diseases.

5.
Int J Environ Res Public Health ; 19(19)2022 Sep 26.
Article in English | MEDLINE | ID: covidwho-2043754

ABSTRACT

Current research has focused on the impacts of the COVID-19 pandemic on university students' physical and mental health conditions but has rarely examined the secondary effects caused by school management and prevention policies. Chinese universities generally took a self-policing strategy to address the COVID-19 pandemic. This study aimed to examine how the self-policing effect fluctuated during the pandemic, assessed from the perspective of university students. We collected monthly data from January 2020 to August 2022 from Zhejiang University's online forum CC98 and analyzed the monthly frequency of keywords in the online posts' titles. The dataset covered five topics: pandemic situations, epidemic prevention policies, campus access control, campus space use, and emotional conditions. The results showed that university students have expressed concern about the pandemic over the past thirty-two months, which still has an unignorable influence on their lives and studies. They paid more attention to the epidemic prevention policies, which directly affected their social connections, spatial use, and psychological well-being. University students gradually questioned their duty to obey and showed impatience and resistance toward school self-policing management, especially during the second Omicron wave. Additionally, the findings investigated an introverted trend for university students living in a gated campus environment. In conclusion, we call for reflections on the current Chinese campus self-policing strategy to cope with future long-term and normalized pandemic situations. The concerns of university students should be taken into account as we move toward a post-COVID-19 world.


Subject(s)
COVID-19 , COVID-19/epidemiology , China/epidemiology , Humans , Pandemics/prevention & control , Students/psychology , Universities
6.
Advanced Engineering Informatics ; 53:101667, 2022.
Article in English | ScienceDirect | ID: covidwho-1906641

ABSTRACT

Site visits or field trips have been a tool utilized by construction educators to engage students in active learning, assist traditional lessons, and attain stronger and deeper student learning experiences. Nevertheless, site visits present major logistical and accessibility challenges for educational institutions and instructors, reducing the number of students that have access to the benefits of such a technique. The limitations for site visits have further broadened recently, as the reality of the COVID-19 public health concerns has forced educators to move to online course delivery quickly and the majority of site visits have been canceled. The research goal of this paper is to present construction students with opportunities to enable online location-independent site visits where contextualized learning is dangerous, unsafe, or impossible to achieve. In this project, a virtual online learning environment was created to offer the affordances that provide an in-depth learning experience through collaborative communication for a plan-reading activity in a virtual space that resembles a real-world site visit to a building facility. This virtual online learning environment helped students to experience the physical and social aspects of the site visit while getting a collaborative opportunity to practice their plan-reading skills. A comparative study with a business-as-usual condition (online delivery through Zoom®) was conducted and the students’ plan-reading performance and their feedback on the sense of presence, social presence, fatigue, and system usability was reported. The outcome of the study shows that such virtual collaborative site visits present unique opportunities to enable online delivery of spatiotemporal contexts of sites and offer an effective remote alternative when these learning opportunities are not available.

7.
Int J Mol Sci ; 23(9)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1847340

ABSTRACT

In this study, humidified air dielectric barrier discharge (DBD) plasma was used to inactivate Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and bacteriophages in biofilms containing DNA, NaCl, carbohydrates, and proteins. The humidified DBD plasma was very effective in the inactivation of microbes in the (≤1.0 µm) biofilms. The number of surviving E. coli, S. aureus, and bacteriophages in the biofilms was strongly dependent on the constituent and thickness of the biofilms and was greatly reduced when the plasma treatment time increased from 5 s to 150 s. Our analysis shows that the UV irradiation was not responsible for the inactivation of microbes in biofilms. The short-lived RONS generated in the humidified air DBD plasma were not directly involved in the inactivation process; however, they recombined or reacted with other species to generate the long-lived RONS. Long-lived RONS diffused into the biofilms to generate very active species, such as ONOOH and OH. This study indicates that the geminated NO2 and OH pair formed due to the homolysis of ONOOH can cause the synergistic oxidation of various organic molecules in the aqueous solution. Proteins in the biofilm were highly resistant to the inactivation of microbes in biofilms, which is presumably due to the existence of the unstable functional groups in the proteins. The unsaturated fatty acids, cysteine-rich proteins, and sulfur-methyl thioether groups in the proteins were easily oxidized by the geminated NO2 and OH pair.


Subject(s)
Bacteriophages , Escherichia coli Infections , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Biofilms , Escherichia coli/physiology , Humans , Nitrogen Dioxide , Staphylococcus aureus/physiology
8.
Front Microbiol ; 13: 858460, 2022.
Article in English | MEDLINE | ID: covidwho-1809436

ABSTRACT

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enterovirus that can cause acute diarrhea and death in piglets and cause serious economic losses to the pig industry. SADS-CoV membrane (M) protein mainly plays a key role in biological processes, such as virus assembly, budding, and host innate immune regulation. Understanding the interaction between M protein and host proteins is very important to define the molecular mechanism of cells at the protein level and to understand specific cellular physiological pathways. In this study, 289 host proteins interacting with M protein were identified by glutathione-S-transferase (GST) pull-down combined with liquid chromatography-mass spectrometry (LC-MS/MS), and the protein-protein interaction (PPI) network was established by Gene Ontology (GO) terms and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways analysis. Results showed that SADS-CoV M protein was mainly associated with the host metabolism, signal transduction, and innate immunity. The Co-Immunoprecipitation (CO-IP) validation results of six randomly selected proteins, namely, Rab11b, voltage-dependent anion-selective channel 1 (VDAC1), Ribosomal Protein L18 (RPL18), RALY, Ras Homolog Family Member A (RHOA), and Annexin A2 (ANXA2), were consistent with LC-MS results. In addition, overexpression of RPL18 and PHOA significantly promoted SADS-CoV replication, while overexpression of RALY antagonized viral replication. This work will help to clarify the function of SADS-CoV M protein in the life cycle of SADS-CoV.

9.
Risk Manag Healthc Policy ; 15: 643-655, 2022.
Article in English | MEDLINE | ID: covidwho-1809141

ABSTRACT

Purpose: Considering high risk of imported epidemic in port cities, it is necessary to estimate COVID-19 vaccine acceptability and to promote vaccination coverage of high-risk occupations. Methods: A cross-sectional survey was carried out among the occupations in Yantai city, China, using an online questionnaire service platform. Targeted strategies were developed based on the survey results. In addition, periodic monitoring of the vaccination rate was provided in order to evaluate the effectiveness of the strategies. Results: A total of 2231 (73.22%) of 3047 participants were willing to accept the vaccine, while 2.53% refused and 24.25% were not sure. Frontline port workers (133/152, 87.50%) and healthcare workers (999/1155, 86.49%) had higher intentions to accept, while public places and commercial service staff (584/1011, 57.76%) had the lowest. The reasons for refusal and hesitation were mainly "doubt of safety or effectiveness" (661/816, 81.00%) and "hearing previous news about vaccines" (455/816, 55.76%). Multilevel strategies such as adequate organizations, health education and promotion, and easy access to vaccination were promoted by local authorities in collaboration with schools, hospitals, enterprises and institutions. The study showed a significant increase in vaccination rate among these occupations after the implementation of these strategies (p<0.001), reaching 87.96%. Conclusion: COVID-19 vaccine acceptability among high-risk occupations was unsatisfactory before the stage of emergency vaccination. An advanced understanding of vaccine attitudes and acceptance can aid in the development of focused immunization promotion programs. It is worth emphasizing that wide strategies with the strong support and enthusiastic cooperation of the government and the industry executive can contribute to increasing occupations' acceptance of the ongoing COVID-19 immunization project.

10.
PLoS One ; 16(11): e0259026, 2021.
Article in English | MEDLINE | ID: covidwho-1496522

ABSTRACT

Interleukin (IL)-33 and its unique receptor, ST2, play a pivotal role in the immune response to infection and stress. However, there have been conflicting reports of the role of IL-33 in cardiovascular disease (CVD) and the potential of this axis in differentiating CVD patients and controls and with CVD disease severity, remains unclear. AIMS: 1) To quantify differences in circulating IL-33 and/or sST2 levels between CVD patients versus controls. 2) Determine association of these biomarkers with mortality in CVD and community cohorts. METHODS AND RESULTS: Using Pubmed/MEDLINE, Web of Science, Prospero and Cochrane databases, systematic review of studies published on IL-33 and/or sST2 levels in patients with CVD (heart failure, acute coronary syndrome, atrial fibrillation, stroke, coronary artery disease and hypertension) vs controls, and in cohorts of each CVD subtype was performed. Pooled standardised mean difference (SMD) of biomarker levels between CVD-cases versus controls and hazard ratios (HRs) for risk of mortality during follow-up in CVD patients, were assessed by random effects meta-analyses. Heterogeneity was evaluated with random-effects meta-regressions. From 1071 studies screened, 77 were meta-analysed. IL-33 levels were lower in HF and CAD patients vs controls, however levels were higher in stroke patients compared controls [Meta-SMD 1.455, 95% CI 0.372-2.537; p = 0.008, I2 = 97.645]. Soluble ST2 had a stronger association with risk of all-cause mortality in ACS (Meta-multivariate HR 2.207, 95% CI 1.160-4.198; p = 0.016, I2 = 95.661) than risk of all-cause mortality in HF (Meta-multivariate HR 1.425, 95% CI 1.268-1.601; p<0.0001, I2 = 92.276). There were insufficient data to examine the association of IL-33 with clinical outcomes in CVD. CONCLUSIONS: IL-33 and sST2 levels differ between CVD patients and controls. Higher levels of sST2 are associated with increased mortality in individuals with CVD. Further study of IL-33/ST2 in cardiovascular studies is essential to progress diagnostic and therapeutic advances related to IL-33/ST2 signalling.


Subject(s)
Interleukin-1 Receptor-Like 1 Protein/metabolism , Interleukin-33/metabolism , Signal Transduction , Acute Coronary Syndrome/metabolism , Cardiovascular Diseases , Case-Control Studies , Cohort Studies , Confidence Intervals , Heart Failure/metabolism , Humans , Multivariate Analysis , Risk Factors , Treatment Outcome
11.
Clin Transl Allergy ; 11(7): e12065, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1439673

ABSTRACT

BACKGROUND: Since the first reports of coronavirus disease 2019 (COVID-19) in Wuhan, China, in December 2019, there have been 198 million confirmed cases worldwide as of August 2021. The scientific community has joined efforts to gain knowledge of the newly emerged virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immunopathological mechanisms leading to COVID-19, and its significance for patients with allergies and asthma. METHODS: Based on the current literature, recent advances and developments in COVID-19 in the context of allergic diseases were reviewed. RESULTS AND CONCLUSIONS: In this review, we discuss the prevalence of COVID-19 in subjects with asthma, attacks of hereditary angioedema, and other allergic diseases during COVID-19. Underlying mechanisms suggest a protective role of allergy in COVID-19, involving eosinophilia, SARS-CoV-2 receptors expression, interferon responses, and other immunological events, but further studies are needed to fully understand those associations. There has been significant progress in disease evaluation and management of COVID-19, and allergy care should continue during the COVID-19 pandemic. The European Academy of Allergy & Clinical Immunology (EAACI) launched a series of statements and position papers providing recommendations on the organization of the allergy clinic, handling of allergen immunotherapy, asthma, drug hypersensitivity, allergic rhinitis, and other allergic diseases. Treatment of allergies using biologics during the COVID-19 pandemic has also been discussed. Allergic reactions to the COVID-19 vaccines, including severe anaphylaxis, have been reported. Vaccination is a prophylactic strategy that can lead to a significant reduction in the mortality and morbidity associated with SARS-CoV-2 infection, and in this review, we discuss the proposed culprit components causing rare adverse reactions and recommendations to mitigate the risk of anaphylactic events during the administration of the vaccines.

13.
Virol Sin ; 35(6): 776-784, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1217480

ABSTRACT

The recent outbreak of novel coronavirus pneumonia (COVID-19) caused by a new coronavirus has posed a great threat to public health. Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients. Virus-encoded proteases are considered potential drug targets. The human immunodeficiency virus protease inhibitors (lopinavir/ritonavir) has been recommended in the global Solidarity Trial in March launched by World Health Organization. However, there is currently no experimental evidence to support or against its clinical use. We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro, and discussed the possible inhibitory mechanism in silico. The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical. Among the four tested compounds, lopinavir showed the best inhibitory effect against the novel coronavirus infection. However, further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen [marketed as Kaletra®, contained lopinavir/ritonavir (200 mg/50 mg) tablets, recommended dosage is 400 mg/10 mg (2 tablets) twice daily]. This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration. Nevertheless, the structure-activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Coronavirus 3C Proteases/antagonists & inhibitors , Lopinavir/pharmacology , Ritonavir/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Viral Protease Inhibitors/pharmacology , Animals , Antiviral Agents/chemistry , COVID-19/blood , COVID-19/virology , Cell Line , Chlorocebus aethiops , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Drug Combinations , Humans , Lopinavir/blood , Male , Molecular Docking Simulation , Ritonavir/blood , Vero Cells , Viral Protease Inhibitors/chemistry
15.
Allergy ; 76(2): 428-455, 2021 02.
Article in English | MEDLINE | ID: covidwho-1140086

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.


Subject(s)
COVID-19 , Critical Illness , Disease Progression , Female , Humans , Male , Risk Factors , SARS-CoV-2
16.
Bioorg Chem ; 107: 104619, 2021 02.
Article in English | MEDLINE | ID: covidwho-1009321

ABSTRACT

Severe emerging and re-emerging viral infections such as Lassa fever, Avian influenza (AI), and COVID-19 caused by SARS-CoV-2 urgently call for new strategies for the development of broad-spectrum antivirals targeting conserved components in the virus life cycle. Viral lipids are essential components, and viral-cell membrane fusion is the required entry step for most unrelated enveloped viruses. In this paper, we identified a porphyrin derivative of protoporphyrin IX (PPIX) that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses including Lassa virus (LASV), Machupo virus (MACV), and SARS-CoV-2 as well as various subtypes of influenza A viral strains with IC50 values ranging from 0.91 ± 0.25 µM to 1.88 ± 0.34 µM. A mechanistic study using influenza A/Puerto Rico/8/34 (H1N1) as a testing strain showed that PPIX inhibits the infection in the early stage of virus entry through biophysically interacting with the hydrophobic lipids of enveloped virions, thereby inhibiting the entry of enveloped viruses into host cells. In addition, the preliminary antiviral activities of PPIX were further assessed by testing mice infected with the influenza A/Puerto Rico/8/34 (H1N1) virus. The results showed that compared with the control group without drug treatment, the survival rate and mean survival time of the mice treated with PPIX were apparently prolonged. These data encourage us to conduct further investigations using PPIX as a lead compound for the rational design of lipid-targeting antivirals for the treatment of infection with enveloped viruses.


Subject(s)
Antiviral Agents/therapeutic use , Orthomyxoviridae Infections/drug therapy , Protoporphyrins/therapeutic use , Virus Internalization/drug effects , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Arenaviruses, New World/drug effects , Chlorocebus aethiops , Dogs , Influenza A Virus, H1N1 Subtype/drug effects , Lassa virus/drug effects , Madin Darby Canine Kidney Cells , Male , Membrane Lipids/metabolism , Mice , Microbial Sensitivity Tests , Protoporphyrins/chemical synthesis , Protoporphyrins/metabolism , Protoporphyrins/pharmacology , SARS-CoV-2/drug effects , Vero Cells , Viral Envelope/drug effects
17.
Cell Discov ; 6(1): 96, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-989763

ABSTRACT

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

18.
arxiv; 2020.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2012.01473v1

ABSTRACT

Automatic lung lesions segmentation of chest CT scans is considered a pivotal stage towards accurate diagnosis and severity measurement of COVID-19. Traditional U-shaped encoder-decoder architecture and its variants suffer from diminutions of contextual information in pooling/upsampling operations with increased semantic gaps among encoded and decoded feature maps as well as instigate vanishing gradient problems for its sequential gradient propagation that result in sub-optimal performance. Moreover, operating with 3D CT-volume poses further limitations due to the exponential increase of computational complexity making the optimization difficult. In this paper, an automated COVID-19 lesion segmentation scheme is proposed utilizing a highly efficient neural network architecture, namely CovSegNet, to overcome these limitations. Additionally, a two-phase training scheme is introduced where a deeper 2D-network is employed for generating ROI-enhanced CT-volume followed by a shallower 3D-network for further enhancement with more contextual information without increasing computational burden. Along with the traditional vertical expansion of Unet, we have introduced horizontal expansion with multi-stage encoder-decoder modules for achieving optimum performance. Additionally, multi-scale feature maps are integrated into the scale transition process to overcome the loss of contextual information. Moreover, a multi-scale fusion module is introduced with a pyramid fusion scheme to reduce the semantic gaps between subsequent encoder/decoder modules while facilitating the parallel optimization for efficient gradient propagation. Outstanding performances have been achieved in three publicly available datasets that largely outperform other state-of-the-art approaches. The proposed scheme can be easily extended for achieving optimum segmentation performances in a wide variety of applications.


Subject(s)
COVID-19 , Bile Duct Diseases , Lung Diseases
20.
Antiviral Res ; 182: 104868, 2020 10.
Article in English | MEDLINE | ID: covidwho-909531

ABSTRACT

COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab')2 fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab')2 inhibited SARS-CoV-2 with an EC50 of 0.07 µg/ml and an EC80 of 0.18 µg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab')2 fragment as a candidate for the treatment of SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Receptors, Immunologic/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Viral/immunology , COVID-19 , Chlorocebus aethiops , Female , HeLa Cells , Humans , Mice, Inbred BALB C , Neutralization Tests , Pandemics , Protein Binding , SARS-CoV-2 , Vero Cells
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