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1.
Infect Drug Resist ; 15: 3295-3307, 2022.
Article in English | MEDLINE | ID: covidwho-1917084

ABSTRACT

Purpose: At present, it has been found that managing patients with a redetected positive RNA test after recovery from foreign-imported coronavirus disease 2019 (COVID-19) cases in China is challenging. The purpose of the current study was to describe the clinical characteristics of these patients. Methods: This retrospective cohort study included 137 COVID-19 patients who were discharged from the Xi'an Public Health Center from 28 July 2020 to 31 December 2021. We compared the clinical characteristics between positive retest patients and non-positive retest patients. Results: 137 COVID-19 patients entered our study, 27 (19.7%) cases of COVID-19 with a redetected positive RNA test by the end of the follow-up period. Fever [(n = 31 (22.6%)], cough [n = 26 (18.9%)] and sore throat [n = 20 (14.5%)] were the most common initial symptoms among the foreign-imported COVID-19 patients, and there were almost no significant differences in initial symptoms between positive retest patients and non-positive retest patients. The positive retest patients had a higher lymphocyte count (p = 0.031) and lymphocyte percentage (p = 0.007) during readmission. There were generally no significant differences in other routine blood test findings, IgG and IgM antibody responses, between positive retest patients and non-positive retest patients, or in positive retest patients over time (before, during, or after positive patient detection). After readmission, positive retest patients displayed fewer symptoms or no obvious disease progression and more sustained remission by CT imaging. Conclusion: Our findings revealed that the clinical characteristics at the time of initial diagnosis were not closely related to redetected positive RNA tests after recovery from foreign-imported COVID-19 cases. Positive retest patients had virtually no symptoms and displayed no obvious disease progression during readmission. These findings provide important information and clinical evidence for the effective management of foreign-imported COVID-19 patients during their convalescent phase.

2.
J Nat Prod ; 85(4): 878-887, 2022 04 22.
Article in English | MEDLINE | ID: covidwho-1805542

ABSTRACT

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/chemistry , COVID-19/drug therapy , Cladosporium , Humans
3.
Methods ; 198: 11-18, 2022 02.
Article in English | MEDLINE | ID: covidwho-1721112

ABSTRACT

Coronavirus Disease-19 (COVID-19) has lead global epidemics with high morbidity and mortality. However, there are currently no proven effective drugs targeting COVID-19. Identifying drug-virus associations can not only provide insights into the understanding of drug-virus interaction mechanism, but also guide and facilitate the screening of compound candidates for antiviral drug discovery. Since conventional experiment methods are time-consuming, laborious and expensive, computational methods to identify potential drug candidates for viruses (e.g., COVID-19) provide an alternative strategy. In this work, we propose a novel framework of Heterogeneous Graph Attention Networks for Drug-Virus Association predictions, named HGATDVA. First, we fully incorporate multiple sources of biomedical data, e.g., drug chemical information, virus genome sequences and viral protein sequences, to construct abundant features for drugs and viruses. Second, we construct two drug-virus heterogeneous graphs. For each graph, we design a self-enhanced graph attention network (SGAT) to explicitly model the dependency between a node and its local neighbors and derive the graph-specific representations for nodes. Third, we further develop a neural network architecture with tri-aggregator to aggregate the graph-specific representations to generate the final node representations. Extensive experiments were conducted on two datasets, i.e., DrugVirus and MDAD, and the results demonstrated that our model outperformed 7 state-of-the-art methods. Case study on SARS-CoV-2 validated the effectiveness of our model in identifying potential drugs for viruses.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Drug Interactions , Humans , Neural Networks, Computer , SARS-CoV-2
4.
Br J Educ Technol ; 53(3): 577-592, 2022 May.
Article in English | MEDLINE | ID: covidwho-1704171

ABSTRACT

The annual instructional virtual team Project X brings together professors and students from across the globe to engage in client projects. The 2020 project was challenged by the global disruption of the COVID-19 pandemic. This paper draws on a quantitative dataset from a post-project survey among 500 participating students and a qualitative narrative inquiry of personal experiences of the faculty members. The findings reveal how innovative use of a variety of collaboration and communication technologies helped students and their professors in building emotional connection and compassion to support each other in the midst of the crisis, and to accomplish the project despite connectivity disruptions. The results suggest that the role of an instructor changed to a coach and mentor, and technology was used to create a greater sense of inclusion and co-presence in student-faculty interactions. Ultimately, the paper highlights the role of technology to help the participants navigate sudden crisis affecting a global online instructional team project. The adaptive instructional teaching strategies and technologies depicted in this study offer transformative potential for future developments in higher education.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320228

ABSTRACT

Background: Numerous studies have been focused on the clinical and imaging features among COVID-19 patients positive for SARS-CoV-2, but the data after negative is limited. We aims to describe these features after negative respiratory nucleic acid testing results.Methods From January 31 to February 28, 2020, 51 mild-to-moderate COVID-19 cases (median: 34.0 years and 47.1% male) were retrospectively enrolled. Demographic, clinical, laboratory, and CT imaging data were collected before and after two sequential negative results for respiratory SARS-CoV-2 .Results After negative for respiratory SARS-CoV-2, the clinical symptoms continued to recover and the abnormal imaging were observed for all of the moderate cases. 77.4% of the moderate patients had multi-lobar involvement and lesions were more frequent in the lower lobes. The most common CT imaging manifestations were ground glass opacity (51.6%) and fibrous stripes (54.8%%). Among 12 out of 31 moderate patients with repeated chest CT scan after negative for SARS-CoV-2, 7 patients (58.3%) with ground-glass absorption reduced over 60% within one week, but there were still 4 cases (13.8%) with absorption less than 5%.Conclusions The clinical symptoms and abnormal imaging persisted but continued to recover after negative for respiratory SARS-CoV-2.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325103

ABSTRACT

Wuhan has the highest number of deaths and mortality from COVID-19 in China to date, but the reason remains unknown. Here we compared patients with COVID-19 with a history of traveling in Wuhan with those who did not travel in Wuhan in the early stage of pandemic with respect to a series of clinical characteristics and laboratory parameters. We observed that patients who had traveled in Wuhan had an increased rate of severe disease and longer viral duration along with fewer CD4 + and CD8 + T cells, although there was no significant difference in viral load between the two groups.

7.
Wireless Communications & Mobile Computing (Online) ; 2021, 2021.
Article in English | ProQuest Central | ID: covidwho-1599316

ABSTRACT

China had made a remarkable headway in online education provision during the first quarter of 2020 due to the coronavirus disease 2019 (COVID-19) outbreak, a global public health crisis that acted as a catalyst for the uptake in online education as a method for students’ e-learning and teachers’ e-teaching at a vast number of institutions worldwide. China’s launching of XuetangX Global and iCourse International, two massive online open course (MOOC) platforms in April 2020 to provide distant e-learning solutions to global learners at a time they were most needed, proves to be a timely move as the global challenge caused by this pandemic turned out to be an opportunity in disguise for online education internationally. This article centers around China’s opportune development in online education and launching university MOOCs internationally in the height of the worsening COVID-19 pandemic in early 2020 and examines its preparedness, implementation, and impact.

9.
Bioinformatics ; 36(19): 4918-4927, 2020 12 08.
Article in English | MEDLINE | ID: covidwho-1387719

ABSTRACT

MOTIVATION: Human microbes play critical roles in drug development and precision medicine. How to systematically understand the complex interaction mechanism between human microbes and drugs remains a challenge nowadays. Identifying microbe-drug associations can not only provide great insights into understanding the mechanism, but also boost the development of drug discovery and repurposing. Considering the high cost and risk of biological experiments, the computational approach is an alternative choice. However, at present, few computational approaches have been developed to tackle this task. RESULTS: In this work, we leveraged rich biological information to construct a heterogeneous network for drugs and microbes, including a microbe similarity network, a drug similarity network and a microbe-drug interaction network. We then proposed a novel graph convolutional network (GCN)-based framework for predicting human Microbe-Drug Associations, named GCNMDA. In the hidden layer of GCN, we further exploited the Conditional Random Field (CRF), which can ensure that similar nodes (i.e. microbes or drugs) have similar representations. To more accurately aggregate representations of neighborhoods, an attention mechanism was designed in the CRF layer. Moreover, we performed a random walk with restart-based scheme on both drug and microbe similarity networks to learn valuable features for drugs and microbes, respectively. Experimental results on three different datasets showed that our GCNMDA model consistently achieved better performance than seven state-of-the-art methods. Case studies for three microbes including SARS-CoV-2 and two antimicrobial drugs (i.e. Ciprofloxacin and Moxifloxacin) further confirmed the effectiveness of GCNMDA in identifying potential microbe-drug associations. AVAILABILITY AND IMPLEMENTATION: Python codes and dataset are available at: https://github.com/longyahui/GCNMDA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
COVID-19 , Microbiota , Pharmaceutical Preparations , Algorithms , Computational Biology , Humans , Pandemics , SARS-CoV-2
10.
Int J Gen Med ; 14: 2069-2078, 2021.
Article in English | MEDLINE | ID: covidwho-1256167

ABSTRACT

BACKGROUND: Effective management of foreign-imported COVID-19 cases is a new and great challenge for China. Our study focused on the foreign-imported COVID-19 cases to provide detailed data for insights into the prevention, early diagnosis, treatment and control of imported COVID-19. METHODS: For this observational and retrospective study, we investigated the clinical characteristics of imported COVID-19 cases that were confirmed by real-time RT-PCR in the Xi'an Public Health Center from 29 March 2020 to 31 August 2020. RESULTS: Of the 79 patients with COVID-19, 19 (24.1%) had exposure to confirmed COVID-19 patients, 15 (19.0%) had exposure to suspicious COVID-19 patients, and 45 (56.9%) had an unclear history of exposure to confirmed patients. The mean age of the patients was 38 years, and 70 (88.7%) patients were male. Except for 2 severe cases, the remaining 58 (73.4%) cases displayed mild or moderate symptoms, and 19 (24.2%) infected patients were asymptomatic. Twenty-one (26.6%) patients were not diagnosed until a third or later nucleic acid test. Ten (12.7%) patients had chronic diseases. The most common manifestations of the patients were cough [18 (22.8%) cases], fever [9 (11.4%) cases] and sore throat [9 (11.4%) cases]. Forty-one (51.9%) cases showed abnormal chest CT images, To date, all patients have been discharged, and no patient has died. CONCLUSION: The imported COVID-19 cases in Xi'an were mainly young and middle-aged adults with mild or moderate symptoms who had a low rate of comorbidity, showed favourable laboratory and chest CT images, and had a better prognosis. Notably, for suspected COVID-19 cases, at least three consecutive nucleic acid tests should be carried out to avoid missed detection of infected patients. Except for severe cases, high-level medical resources are not necessary in most cases.

11.
PLoS One ; 16(4): e0249481, 2021.
Article in English | MEDLINE | ID: covidwho-1197372

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) remains a global challenge. Corticosteroids constitute a group of anti-inflammatory and immunosuppressive drugs that are widely used in the treatment of COVID-19. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19. METHODS: We conducted a comprehensive literature review and meta-analysis of research articles, including observational studies and clinical trials, by searching the PubMed, EMBASE, Cochrane Controlled Trials Registry, and China Academic Journal Network Publishing databases. Patients treated between December 1, 2019, and January 1, 2021, were included. The outcome measures were the proportion of patients treated with corticosteroids, viral clearance and mortality. The effect size with the associated 95% confidence interval is reported as the weighted mean difference for continuous outcomes and the odds ratio for dichotomous outcomes. RESULTS: Fifty-two trials involving 15710 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids (35.19% vs. 64.49%). In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere cases treated with corticosteroids (27.91% vs. 20.91%). We also performed subgroup analyses stratified by whether patients stayed in the intensive care unit (ICU) and found that the proportion of patients who received corticosteroids was significantly higher among those who stayed in the ICU than among those who did not. The results of our meta-analysis indicate that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference in the use of corticosteroids for COVID-19 between patients who died and those who survived. This result indicates that mortality is not correlated with corticosteroid therapy. CONCLUSION: The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 infections delayed viral clearance and did not convincingly improve survival; therefore, corticosteroids should be used with extreme caution in the treatment of COVID-19.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/virology , Humans , Intensive Care Units , Randomized Controlled Trials as Topic , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Treatment Outcome
12.
J Med Virol ; 93(1): 448-455, 2021 01.
Article in English | MEDLINE | ID: covidwho-1196394

ABSTRACT

This study investigates the clinical and imaging characteristics of coronavirus disease 2019 (COVID-19) patients with false-negative nucleic acids. Mild-to-moderate COVID-19 patients, including 19 cases of nucleic acid false-negative patients and 31 cases of nucleic acid positive patients, were enrolled. Their epidemiological, clinical, and laboratory examination data and imaging characteristics were analyzed. Risk factors for false negatives were discussed. Compared with the nucleic acid positive group, the false-negative group had less epidemiological exposure (52.6% vs 83.9%; P = .025), less chest discomfort (5.3% vs 32.3%; P = .035), and faster recovery (10 [8, 13] vs 15 [11, 18.5] days; P = .005). The number of involved lung lobes was (2 [1, 2.5] vs 3 [2, 4] days; P = .004), and the lung damage severity score was (3 [2.5, 4.5] vs 5 [4, 9] days; P = .007), which was lighter in the nucleic acid false-negative group. Thus, the absence of epidemiological exposure may be a potential risk factor for false-negative nucleic acids. The false-negative cases of COVID-19 are worth noting because they have a risk of viral transmission without positive test results, lighter clinical manifestations, and less history of epidemiological exposure.


Subject(s)
COVID-19/pathology , SARS-CoV-2/isolation & purification , Adult , COVID-19/diagnostic imaging , False Negative Reactions , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Male , RNA, Viral/blood , Risk Factors , Young Adult
13.
BMC Infect Dis ; 21(1): 333, 2021 Apr 08.
Article in English | MEDLINE | ID: covidwho-1175295

ABSTRACT

BACKGROUND: The clinical and imaging features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections that progressed to coronavirus disease 2019 (COVID-19) have been explored in numerous studies. However, little is known about these features in patients who received negative respiratory nucleic acid test results after the infections resolved. In this study, we aim to describe these features in a group of Chinese patients. METHODS: This retrospective study includes 51 patients with mild-to-moderate COVID-19 (median age: 34.0 years and 47.1% male) between January 31 and February 28, 2020. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were collected before and after two consecutive negative respiratory SARS-CoV-2 tests. RESULTS: Following a negative test result, the patients' clinical symptoms continued to recover, but abnormal imaging findings were observed in all moderate cases. Specifically, 77.4% of patients with moderate COVID-19 exhibited multi-lobar lung involvement and lesions were more frequently observed in the lower lobes. The most common CT imaging manifestations were ground-glass opacities (51.6%) and fibrous stripes (54.8%%). Twelve of the 31 patients with moderate COVID-19 underwent repeated chest CT scans after a negative SARS-CoV-2 test. Among them, the ground-glass opacities decreased by > 60% within 1 week in seven patients (58.3%), but by < 5% in four patients (13.8%). CONCLUSIONS: Following a positive and subsequent negative SARS-CoV-2 tests, patients with COVID-19 continued to recover despite exhibiting persistent clinical symptoms and abnormal imaging findings.


Subject(s)
COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , COVID-19 Nucleic Acid Testing , Female , Humans , Lung/diagnostic imaging , Male , Retrospective Studies
14.
Open Medicine ; 16(1):332-337, 2021.
Article in English | ProQuest Central | ID: covidwho-1119485

ABSTRACT

We compared the clinical characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive and negative anal swabs during coronavirus disease 2019 (COVID-19) recovery and investigated the clinical significance and influence factors of anal swab detection.This study retrospectively analyzed 23 moderate COVID-19 patients in the recovery phase. They were divided into anal swab positive group (n = 13) (negative for pharyngeal swabs but positive for anal swabs) and anal swab negative group (n = 10) (negative for pharyngeal and anal swabs). The epidemiology, clinical symptoms, time of pharyngeal swabs turning negative, and laboratory results were compared.The time of pharyngeal swabs turning negative in the anal swab positive group was 6 (5–8.5) days, significantly longer than that in the anal swab negative group (1 (1–4.25) days), P = 0.0002). The platelet count of the anal swab positive group was significantly lower than that of the anal swab negative group (198 (135–235) × 109/L vs 240.5 (227–264.75) × 109/L, P = 0.0248). No significant difference was observed between the two groups in other variables.The time of pharyngeal swab turning negative in anal swab positive patients is longer than that in anal swab negative patients. The platelet count can be used as an indicator for viral infection evaluation. For patients with a longer time of pharyngeal swabs turning negative, the combined testing of the anal swab and platelet counts may help to avoid pharyngeal swab false negatives, premature discharge, and the possibility of fecal-oral transmission.

15.
Front Immunol ; 12: 603563, 2021.
Article in English | MEDLINE | ID: covidwho-1090415

ABSTRACT

The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, with decreased IFNγ expression in CD4+ T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Killer Cells, Natural/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Cell Count , Cells, Cultured , Disease Progression , Female , Humans , Immunity, Cellular , Interferon-gamma/metabolism , Male , Middle Aged
16.
Biomed Res Int ; 2020: 6342598, 2020.
Article in English | MEDLINE | ID: covidwho-955428

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children accounts for a small proportion of all infections and is usually mild or asymptomatic. There are few studies on the clinical characteristics of SARS-CoV-2 infection in children, and the causes of the low prevalence in children remain unclear. Herein, we compared the epidemiological and clinical characteristics of SARS-CoV-2 infection between adults and children. Fifty-two patients with Coronavirus Disease 2019 (COVID-19) were retrospectively analyzed, including 38 adults and 14 children. Their clinical information such as epidemiological exposure history, laboratory indicators, chest computed tomography (CT) performance, and number of SARS-CoV-2 positive days were analyzed and compared. In children, 5 (35.71%) had mild COVID-19 and 9 (64.29%) had common type, while, in adults, 9 (23.68%) cases were mild, and 29 (76.32%) were common COVID-19. Among them, family clustering infection accounted for 50% (7/14) of child cases and 23.68% (9/36) of adult cases. Epidemiological exposure history, clinical classification, clinical symptoms, chest CT manifestations, and number of SARS-CoV-2-positive days were not significantly different between children and adults. However, the percentage of neutrophils in adults was significantly higher than that in children (P < 0.05). The percentage and absolute value of lymphocytes, platelet counts, aspartate aminotransferase, and aspartate aminotransferase/alanine aminotransferase in adults were lower than those in children (P < 0.05). Conclusively, children infected with SARS-CoV-2 show the characteristics of family clustering, and the proportion of mild and asymptomatic infections is higher. For families with a history of epidemiological exposure, routine SARS-CoV-2 nucleic acid testing and chest CT examination should be performed in asymptomatic children to determine whether they are infected. Unlike adults, although the reduction of lymphocytes and platelets in children is not common, it is necessary to be alert to the increased risk of liver damage in children.


Subject(s)
COVID-19 , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Blood Platelets/metabolism , COVID-19/blood , COVID-19/diagnostic imaging , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Leukocyte Count , Male , Middle Aged , Neutrophils/metabolism , Platelet Count , SARS-CoV-2
17.
Journal of Third Military Medical University ; 42(06):539-544, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-833506

ABSTRACT

2019 coronavirus disease (COVID-19) is an infectious disease caused by SARS-COV-2 virus, and lacks specifically effective treatment till now. Its clinical manifestations and the concerning studies at home and abroad have shown that viral sepsis caused by SARS-COV-2 virus has typical characteristics of pathophysiology of sepsis, that is, early cytokine storm and subsequent immunosuppression stage. At present, although great attention has been paid to the treatment and clinical research on cytokine storm, the later stage of immunosuppression is neglected. Patients' lower immunity, secondary infection and multiple organ failure are quite common, and all these lead to rapid deterioration and even death. Therefore, it is of great significance to pay attention to the investigation and treatment of sepsis immunosuppression stage caused by COVID-19, and to study the drugs with bidirectional immune regulation such as artesunate so as order to reduce the mortality of patients with severe or critical COVID-19. What's more, we strongly recommend that chloroquine phosphate should be used with great caution for severe and critical patients.

18.
Br J Pharmacol ; 177(18): 4147-4165, 2020 09.
Article in English | MEDLINE | ID: covidwho-592492

ABSTRACT

BACKGROUND AND PURPOSE: Immunosuppression is the predominant cause of mortality for sepsis because of failure to eradicate pathogens. No effective and specific drugs capable of reversing immunosuppression are clinically available. Evidences implicate the involvement of the vitamin D receptor (NR1I1) in sepsis-induced immunosuppression. The anti-malarial artesunate was investigated to determine action on sepsis-induced immunosuppression. EXPERIMENTAL APPROACH: The effect of artesunate on sepsis-induced immunosuppression was investigated in mice and human and mice cell lines. Bioinformatics predicted vitamin D receptor as a candidate target for artesunate, which was then identified using PCR and immunoblotting. Vdr, Atg16l1 and NF-κB p65 were modified to investigate artesunate 's effect on pro-inflammatory cytokines release, bacterial clearance and autophagy activities in sepsis-induced immunosuppression. KEY RESULTS: Artesunate significantly reduced the mortality of caecal ligation and puncture (CLP)-induced sepsis immunosuppression mice challenged with Pseudomonas aeruginosa and enhanced pro-inflammatory cytokine release and bacterial clearance to reverse sepsis-induced immunosuppression in vivo and in vitro. Mechanistically, artesunate interacted with vitamin D receptor, inhibiting its nuclear translocation, which influenced ATG16L1 transcription and subsequent autophagy activity. Artesunate inhibited the physical interaction between vitamin D receptor and NF-κB p65 in LPS-tolerant macrophages and then promoted the nuclear translocation of NF-κB p65, which activated the transcription of NF-κB p65 target genes such as pro-inflammatory cytokines. CONCLUSION AND IMPLICATIONS: Our findings provide evidence that artesunate interacted with vitamin D receptor to reverse sepsis-induced immunosuppression in an autophagy and NF-κB-dependent manner, highlighting a novel approach for sepsis treatment and drug repurposing of artesunate has a bidirectional immunomodulator.


Subject(s)
Artesunate , Autophagy , Receptors, Calcitriol , Sepsis , Animals , Artesunate/pharmacology , Female , Male , Mice , Mice, Inbred BALB C , NF-kappa B , Receptors, Calcitriol/drug effects , Sepsis/drug therapy
19.
Immunity ; 52(6): 971-977.e3, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-155320

ABSTRACT

The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Immunity, Cellular , Immunity, Humoral , Pneumonia, Viral/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 , Convalescence , Coronavirus Infections/blood , Coronavirus Infections/pathology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
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