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1.
Front Med (Lausanne) ; 9: 850374, 2022.
Article in English | MEDLINE | ID: covidwho-1855383

ABSTRACT

The profound effects of and distress caused by the global COVID-19 pandemic highlighted what has been known in the health sciences a long time ago: that bacteria, fungi, viruses, and parasites continue to present a major threat to human health. Infectious diseases remain the leading cause of death worldwide, with antibiotic resistance increasing exponentially due to a lack of new treatments. In addition to this, many pathogens share the common trait of having the ability to modulate, and escape from, the host immune response. The challenge in medical microbiology is to develop and apply new experimental approaches that allow for the identification of both the microbe and its drug susceptibility profile in a time-sensitive manner, as well as to elucidate their molecular mechanisms of survival and immunomodulation. Over the last three decades, proteomics has contributed to a better understanding of the underlying molecular mechanisms responsible for microbial drug resistance and pathogenicity. Proteomics has gained new momentum as a result of recent advances in mass spectrometry. Indeed, mass spectrometry-based biomedical research has been made possible thanks to technological advances in instrumentation capability and the continuous improvement of sample processing and workflows. For example, high-throughput applications such as SWATH or Trapped ion mobility enable the identification of thousands of proteins in a matter of minutes. This type of rapid, in-depth analysis, combined with other advanced, supportive applications such as data processing and artificial intelligence, presents a unique opportunity to translate knowledge-based findings into measurable impacts like new antimicrobial biomarkers and drug targets. In relation to the Research Topic "Proteomic Approaches to Unravel Mechanisms of Resistance and Immune Evasion of Bacterial Pathogens," this review specifically seeks to highlight the synergies between the powerful fields of modern proteomics and microbiology, as well as bridging translational opportunities from biomedical research to clinical practice.

2.
iScience ; 25(4): 104136, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1851358

ABSTRACT

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to public health. Human breast milk is a complex nutritional composition to nourish infants and protect them from different kinds of infectious diseases including COVID-19. Here, we identified that lactoferrin (LF), mucin1 (MUC1), and α-lactalbumin (α-LA) from human breast milk inhibit SARS-CoV-2 infection using a SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). In addition, LF and MUC1 inhibited multiple steps including viral attachment, entry, and postentry replication, whereas α-LA inhibited viral attachment and entry. Importantly, LF, MUC1, and α-LA possess potent antiviral activities toward variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.1 (kappa). Taken together, our study provides evidence that human breast milk components (LF, MUC1, and α-LA) are promising antiviral and potential therapeutic candidates warranting further development for treating COVID-19.

3.
iScience ; 2022.
Article in English | EuropePMC | ID: covidwho-1755857

ABSTRACT

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is a complex with nutritional composition to nourish infants and protect them from different kinds of infectious diseases including COVID-19. Here, we identified lactoferrin (LF), mucin1 (MUC1) and α-lactalbumin (α-LA) from human breastmilk inhibit SARS-CoV-2 infection using a SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). Additionally, LF and MUC1 inhibited multiple steps including viral attachment, entry and post-entry replication, while α-LA inhibited viral attachment and entry. Importantly, LF, MUC1 and α-LA possessed potent antiviral activities towards variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Taken together, our study provides evidence that human breastmilk components (LF, MUC1 and α-LA) are promising antiviral and potential therapeutic candidates warranting further development or treating COVID-19. Graphical

4.
Heart Lung ; 53: 51-60, 2022.
Article in English | MEDLINE | ID: covidwho-1693436

ABSTRACT

BACKGROUND: Convalescent plasma treatment for severe and critically ill Corona Virus Disease 2019 (COVID-19) patients remains controversial. OBJECTIVE: To evaluate the clinical improvement and mortality risk of convalescent plasma treatment in patients with severe and critically ill COVID-19 patients. METHODS: A literature search was conducted in the electronic databases for the randomized controlled studies about convalescent plasma therapy in severe and critically ill COVID-19 patients. Two reviewers independently extracted relevant data. The primary outcomes were clinical improvement and mortality risk of severe and critically ill COVID-19 patients that were therapied by convalescent plasma. RESULTS: A total of 14 randomized controlled trials with 4543 patients were included in this meta-analysis. Compared to control, no significant difference was observed for either clinical improvement (6 studies, RR 1.07, 95% CI 0.97 to 1.17, p = 0.16, moderate certainty) or mortality risk (14 studies, RR 0.94, 95% CI 0.85 to 1.03, p= 0.18, low certainty) in patients of convalescent plasma therapy group. CONCLUSION: Convalescent plasma did not increase the clinical improvement or reduce the mortality risk in the severe and critically ill COVID-19 patients.


Subject(s)
COVID-19 , COVID-19/therapy , Critical Illness/therapy , Humans , Immunization, Passive/adverse effects , Randomized Controlled Trials as Topic
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324491

ABSTRACT

Background: Convalescent plasma treatment of severe and critically ill Corona Virus Disease 2019(COVID-19) patients is still controversial. Objective: To evaluate the efficacy and safety of convalescent plasma in patients with severe COVID-19 infection and critically ill patients, We performed a meta-analysis and systematic review of convalescent plasma therapy in severe and critically ill COVID-19 patients. Methods: : We conducted a literature search in electronic data and citations of previously published systematic reviews. We included only randomized controlled studies on convalescent plasma for the treatment of severe and critically ill COVID-19 patients. Results: : A total of 7 randomized controlled trials and 1363 patients were included in the meta-analysis. Compared to patients of the control group, there was no difference in clinical improvement (Four studies, RR 1.06, 95% CI 0.96 to 1.17, p = 0.22, moderate certainty) and mortality (seven studies, RR 0.86, 95% CI 0.66 to 1.11, p = 0.48, moderate certainty) for patients of convalescent plasma therapy group. Conclusion: Convalescent plasma does not reduce the improvement of symptoms and the risk of death in severely infected and critically ill COVID-19 patients

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323763

ABSTRACT

Abstract Backgroud: To describe the frequency and distribution characteristics of gastrointestinal symptoms of coronavirus disease 2019 (COVID-19) patients.Methods: As a cohort study, all confirmed COVID-19 patients with gastrointestinal symptoms at Xiangyang No.1 people’s hospital were included until February 21st, 2020. Course of disease no less than 21 days.Gastrointestinal symptoms relevant data were extracted and analyzed. The frequency histograms of the symptoms were plotted. Main symptom characteristics were summarized.Results: Of 50 included patients with gastrointestinal symptoms, 21 were male, 29were female. The mean age was 53 (SD 16) years. Course of disease ranged from 21 to 34 days with a median of 26 days. Among all patients, 16 were critically ill and five died, 12 discharged. Thirty-one clinical symptoms occurred 3168 times in total, 6 gastrointestinal symptoms occurred 439 (13.86%) times and 25 non-gastrointestinal symptoms occurred 2 729(86.14%) times. All symptoms and non-gastrointestinal symptoms distributed in 1 to 34 days, reached peak on 6th day of follow up, first seven days were the fastigium and decreasing in the rest days. Gastrointestinal symptoms mainly distributed in 1 to 34 days, reached a peak of 36 times per day on 6th of follow-up with a fastigium during 6 to 12 day, showed a trend of rise first and then fall. Nausea, vomit and abdominal discomfort occurred 133, 70 and 62 times, respectively.Conclusions: A symptom frequency to time distribution model could describe the disease process quantitatively, indicating the change law of gastrointestinal symptoms and the organ damages in gastrointestinal system, could help us to better understand and treat the new disease. Females showed higher incidence of gastrointestinal symptoms, whether there is a sex difference in susceptibility needs to be further confirmed.Trial regitration: retrospectively registeredAuthors Guoxin Huang and Shengduo Pei contributed equally to this work.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312652

ABSTRACT

Human beings are constantly struggling with various epidemics. Although we gained a lot of experience and success, in the face of the new epidemic, we still inevitably face pressure from public health, politics, and the economy. Case fatality ratio (CFR) received widespread attention as one of the indicators describing the severity of the epidemic and evaluating treatment options. However, due to the ongoing epidemic situation and the constant changes in the death and diagnosis data, no scientific method for this situation to calculate the CFR exists. This study proposes a method for estimating CFR in the continuation of the epidemic. CFR is estimated by "ratio of the cumulative number of deaths before j days from a given day to the sum of the number of patients discharged from a given day and the cumulative number of deaths before j days from a given day ". Take the ongoing outbreak of COVID COVID-19 in December 2019 as an example. The results show that, regardless of the size of the estimated value or its changing trend, the estimated CFR given by the new method shows better stability and better reflects the true situation of the case fatality rate;additionally, the improvement of medical conditions can also be clearly reflected in the change in valuation. When j = 10, according to the data of March 10, the CFR of COVIDCOVID-19 in Wuhan, China and China (excluding Hubei)is 6.23%,4.46%, and 0.87%, respectively. This method of estimating CFR can be used in time to evaluate the therapeutic effect of different medical schemes and different regions, which is of great value and significance for the decision decision-making in the epidemicprevention and control.Authors Wanling Hu, Xiaoyun Liu, and Tao Wang contributed equally to this work

8.
Front Med (Lausanne) ; 7: 611460, 2020.
Article in English | MEDLINE | ID: covidwho-1389196

ABSTRACT

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

9.
Infect Dis Poverty ; 10(1): 72, 2021 May 18.
Article in English | MEDLINE | ID: covidwho-1236574

ABSTRACT

BACKGROUND: Given the context of rapid technological change and COIVD-19 pandemics, E-learning may provide a unique opportunity for addressing the challenges in traditional face-to-face continuing medical education (CME). However, the effectiveness of E-learning in CME interventions remains unclear. This study aims to evaluate whether E-learning training program can improve TB health personnel's knowledge and behaviour in China. METHODS: This study used a convergent mixed method research design to evaluate the impact of E-learning programs for tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change during the China-Gates TB Project (add the time span). Quantitative data was collected by staff surveys (baseline n = 555; final n = 757) and management information systems to measure the demographic characteristics, training participation, and TB knowledge. Difference-in-difference (DID) and multiple linear regression models were employed to capture the effectiveness of knowledge improvement. Qualitative data was collected by interviews (n = 30) and focus group discussions (n = 44) with managers, teachers, and learners to explore their learning experience. RESULTS: Synchronous E-learning improved the knowledge of TB clinicians (average treatment effect, ATE: 7.3 scores/100, P = 0.026). Asynchronous E-learning has a significant impact on knowledge among primary care workers (ATE: 10.9/100, P < 0.001), but not in clinicians or public health physicians. Traditional face-to-face training has no significant impact on all medical staff. Most of the learners (57.3%) agreed that they could apply what they learned to their practice. Qualitative data revealed that high quality content is the key facilitator of the behaviour change, while of learning content difficulty, relevancy, and hardware constraints are key barriers. CONCLUSIONS: The effectiveness of E-learning in CME varies across different types of training formats, organizational environment, and target audience. Although clinicians and primary care workers improved their knowledge by E-learning activities, public health physicians didn't benefit from the interventions.


Subject(s)
Computer-Assisted Instruction , Tuberculosis , China , Education, Medical, Continuing , Health Personnel/education , Humans , Tuberculosis/prevention & control
10.
Cell Biosci ; 11(1): 45, 2021 Feb 28.
Article in English | MEDLINE | ID: covidwho-1105737

ABSTRACT

BACKGROUND: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.

11.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-4483

ABSTRACT

Objective Based on the systematic pharmacol. database of traditional Chinese medicine (TCM) and the anal. platform TCMSP, the computer virtual screening technique was used to find the small mol. inhibitors of TCM for SARS-CoV-2 3CL hydrolase, and to speculate the potential anti-COVID-19 novel coronavirus pneumonia TCMs and traditional Chinese Herbal Compounds Methods SARS-CoV-2 3CL hydrolase protein was targeted in this study. Autodock Vina software and Python script were used to realize high-throughput mol. docking. Combined with "ADME-Lipinski" rules, the re-screening was carried out to optimize the active ingredients and to speculate the key TCMs and compound prescriptions. Based on the perspective of network pharmacol., a component-target-pathway network was constructed to infer the mechanism of action of core drug pairs. Results Taking lopinavir/ritonavir compound preparation as pos. control, 66 natural micromol. compounds with good pharmacokinetic properties were screened out, so that 66 natural micromol. inhibitors with good pharmacokinetic properties were obtained. Eleven single TCMs, two Chinese medicine pairs of Licorice-Mori Cortex and Lonicerae Japonicae Flos-Forsythiae Fructus, and twelve TCM prescriptions including Sangju Drink and Modified Sangju Drink and Yinqiao Powder were selected as candidate schemes to fight against novel coronavirus pneumonia. Conclusion This study is based on high-throughput mol. docking technol. to virtually screen small mol. inhibitors of SARS-CoV-2 3CL hydrolase of TCM and Chinese herbal medicines, innovatively analyze the potential mol. mechanism in combination with network pharmacol., and provide scientific guidance and theor. basis for TCM to resist novel coronavirus pneumonia.

12.
J Prim Care Community Health ; 11: 2150132720975517, 2020.
Article in English | MEDLINE | ID: covidwho-937038

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly-identified infectious diseases that has rapidly spread throughout the world with rising fatalities with declaration by World Health Organization as the pandemic. Online consultations have been shown to alleviate the pandemic with our study aims to demonstrate whether online consultation can be a solution for acute health crisis. Retrospective analysis of the characteristics of online consultations through two primary care online-consultation platforms during COVID-19 pandemic was performed at the Third Affiliated Hospital of Sun Yat-Sen University, which led the assessment of COVID-19-symptoms patients in Guangzhou. The 3473 online consultations were divided into pre-pandemic and pandemic period groups with Chi-square test as statistical analysis method. The number of online consultations has increased with diagnosis of upper respiratory tract infection, psychological conditions, COVID-19-related investigations and interventions. The increased online consultations met the increased demand of the relevant clinical services and reduced the overwhelming hospital presentations, thus decreasing the potential COVID-19 spread inside the major tertiary hospital and sparing the resources for acute crisis management. The epidemiology and disease characteristics of online consultations during the pandemic have been demonstrated with identification of the enabling factors and potential barriers in improving online healthcare in China with online consultation model being a durable solution for pandemic in future.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Remote Consultation/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , China , Female , Humans , Male , Middle Aged , Pandemics , Primary Health Care/statistics & numerical data , Retrospective Studies , Tertiary Care Centers , Young Adult
13.
Chinese Science Bulletin ; 65(22):2342-2350, 2020.
Article | WHO COVID | ID: covidwho-740395

ABSTRACT

The COVID-19 outbreak has been associated with over 250000 confirmed infections and over 11000 confirmed deaths worldwide. The epidemic poses a huge challenge to global public health security. Cure rate (CR)/case fatality rate (CFR) is an important data to assess the severity of an epidemic disease and an important consideration to evaluate the therapeutic effect. The current calculation of CR or CFR for COVID-19 epidemic is based on formula: number of cure or deaths/number of diagnosed. This calculation method was called crude CR/CFR. However, there is no more scientific method to calculate the CR and CFR of the epidemic due to the changing data of the epidemic, especially the large increase of the number of diagnosed and hospitalized. The estimated CFR calculated by the basic formula is called crude CFR. Considering a large number of hospitalized patients, we revised the calculation method for CR, which is the ratio of cumulative discharges on a given day to the sum of cumulative discharges on a given day and cumulative deaths before j days is used to estimate the CR. In addition, the CFR can be estimated accordingly. According to statistical theory, if the COVID-19 epidemic event satisfies the statistical random event hypothesis, the estimated daily CR and CFR rate should be basically stable without considering the discovery of future special drugs and special medical methods. Therefore, the j value is selected with the minimum variance or coefficient of variation of the daily estimate of CR as the selection index, and the best value of j is determined by reference to clinical observation statistics. According to the results, the coefficient of variation of the estimated CR of Wuhan, Hubei, China, Hubei excluding Wuhan and China excluding Hubei reached the minimum value at j=8,10,10,10 and 12, respectively, indicating that this is the least difference in the estimated value of each day. When j=9, the CR of COVID-19 was estimated to be about 95.8% in China, while the CFR was estimated to be about 4.2%, which is lower than that of the SARS epidemic in mainland China in 2003;the CR in Wuhan was estimated to be about 94.5%, while the CFR in Wuhan was estimated to be about 5.5%. Because of the large number of cases and low cure rate in Wuhan, the cure rate in Hubei Province is lower than the national average. The CR of Hubei excluding Wuhan was similar to the national average. The CR of China excluding Hubei Province is the highest, which may be related to the factors of more imported cases, different age structure of imported cases, relatively few patients and better treatment conditions in the other provinces. This method of estimating the CR optimized the calculation method of crude CR, considering the influence of the population still in hospital on the valuation. So the comparatively accurate CR/CFR predictions for the ongoing epidemics are conducive to decision making regarding epidemic prevention and control as well as evaluating the curative effects of availed treatments.

14.
Chin. Trad. Herbal Drugs ; 6(51): 1397-1405, 20200328.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-378401

ABSTRACT

Objective: Based on the systematic pharmacological database of traditional Chinese medicine (TCM) and the analysis platform TCMSP, the computer virtual screening technique was used to screen the small molecule inhibitors of SARS-CoV-2 3CL hydrolase from Chinese materia medica (CMM), and speculate the potential anti-COVID-19 novel coronavirus pneumonia TCMs and its compounds. Methods: SARS-CoV-2 3CL hydrolase protein was targeted in this study. Autodock Vina software and Python script were used to realize high-throughput molecular docking. Combined with “ADME-Lipinski” rules, the re-screening was carried out to optimize the active ingredients and speculate the key TCMs and compound prescriptions. Based on the perspective of network pharmacology, a component-target-pathway network was constructed to infer the mechanism of action of core drug pairs. Results: Taking the reference ligand as positive control, 66 natural micromolecule compounds with good pharmacokinetic properties were obtained. Twelve single TCMs, two Chinese medicine pairs of Glycyrrhizae Radix et Rhizoma-Mori Cortex and Lonicerae Japonicae Flos-Forsythiae Fructus, and 12 TCM prescriptions including Sangju Drink and modified Sangju Drink and Yinqiao Powder were selected as candidate schemes to fight against novel coronavirus pneumonia. Conclusion: This study is based on high-throughput molecular docking technology to virtually screen small molecule inhibitors of SARS-CoV-2 3CL hydrolase of CMM and Chinese medicines, innovatively analyze the potential molecular mechanism in combination with network pharmacology, and provide scientific guidance and theoretical basis for TCM to resist novel coronavirus pneumonia.

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