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1.
Front Public Health ; 10: 763490, 2022.
Article in English | MEDLINE | ID: covidwho-1834635

ABSTRACT

Aim: Following the outbreak of the COVID-19 epidemic, China adopted community isolation management measures. During the "lockdown" period, urban communities were the most basic prevention and control unit for the epidemic. The effectiveness of community epidemic prevention directly affects the spread of the virus and social stability. Therefore, the aim of this study was to explore the status quo and influencing factors of psychological distress. Methods: For this study, 1,430 community households were randomly selected in key cities affected by the epidemic, and a questionnaire survey was administered during the lockdown period. A structural equation model was used to analyse the influencing factors of community epidemic prevention effects. A total of 1,326 valid questionnaires were collected, with a valid response rate of 92.73%. Results: In this study, the differences in psychological distress among different community types were statistically significant (t = 58.41, P < 0.01). The results showed that epidemic prevention capability played a mediating role. The results of the high-order structural equation model analysis showed that perceived social support (ß = -0.275, P = 0.000) and community social network (ß = -0.296, P < 0.01) were significantly negatively correlated with psychological distress. Conclusions: Community social support indirectly relieves psychological anxiety and improves the effect of epidemic prevention by enhancing residents' ability to prevent epidemics. The community social network help residents reduce the risk of outbreaks and indirectly alleviate psychological distress.


Subject(s)
COVID-19 , Epidemics , Psychological Distress , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Humans , SARS-CoV-2 , Social Networking , Social Support
2.
Ocean Coast Manag ; 224: 106171, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1814999

ABSTRACT

COVID-19 has had a huge impact on the global container market. Many liner companies have adopted a blank sailing for some voyages to adjust capacity, and vessel schedule reliability continues to be sluggish. From the perspective of the container liner company, this paper studies the integrated recovery of liner schedule and container flow under the background of suspension of shipping service. With the goal of minimizing the total cost of the liner company, the hard time window constraints of the container flow on the suspended routes are set to construct the integrated recovery problem.The increased carbon emission cost during the restoration of the container flow is taken into account.A mixed integer nonlinear programming model is established, and the adaptive mutation particle swarm optimization (AMPSO) is used to solve the model. The results show that the total cost of the model is reduced by 10.66% compared with the total cost of the shipping schedule recovery model that did not consider the recovery of container flow.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322144

ABSTRACT

Background: Nosocomial infections (NIs) are an important cause of mortality, and increasing evidence reveals that the prevalence of NIs can be reduced through effective prevention and control measures. The aim of this study was to investigate the impact of the prevention and control measures for the COVID-19 pandemic on NIs. Methods: : A retrospective study was conducted to analyze the prevalence of NIs before and after COVID-19 pandemic for six months in the Children’s Hospital of Soochow University. Results: : A total of 39,914 patients in 2019 and 34,645 patients in 2020 were admitted to the hospital during the study. There were 1.39% (481/34645) of patients with NIs in 2020, which was significantly lower than the 2.56% (1021/39914) of patients in 2019. The rate of critical and fatal cases was also decreased. Except for the ICU, the prevalence of nosocomial infection in most departments decreased from 2019 to 2020. Regarding the source of infections, a significant reduction was mainly observed in respiratory (0.99% vs 0.42%, p=0.000) and digestive tract (0.63% vs 0.14%, p=0.000). The microorganism analysis of respiratory infections indicated an obvious decline in acinetobacters and fungi. The most significant decline of pathogens in gastrointestinal infections was observed for rotavirus. The comparison of catheter-related nosocomial infections between 2019 and 2020 did not show significant differences. Conclusions: : The prevention and control measures for the COVID-19 pandemic have reduced the nosocomial infection in almost all departments, except the ICU, mainly regarding respiratory, gastrointestinal, and oral infections, while catheter-related infections did not show any differences.

4.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750478

ABSTRACT

A recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG) inhibits SARS-CoV-2 PLpro-catalyzed viral polyprotein cleavage and ISG15 deconjugation in cells and inhibits replication of SARS-CoV-2 in Vero-E6 cells and Calu3 cells at submicromolar levels. As a well-characterized FDA-approved orally delivered drug, 6-TG represents a promising therapeutic for COVID-19 and other emerging coronaviruses. One Sentence Summary: A repurposed drug that targets an essential enzymatic activity of SARS-CoV-2 represents a promising COVID-19 therapeutic.

5.
J Ethnopharmacol ; 285: 114838, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1509996

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.


Subject(s)
Acute Lung Injury , Antiviral Agents/pharmacology , Bronchoalveolar Lavage Fluid , COVID-19 , Drugs, Chinese Herbal/pharmacology , Lung , Acute Lung Injury/drug therapy , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Animals , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Capsules , Chemokine CXCL2/analysis , Coix , Forsythia , Interleukin-1beta/analysis , Interleukin-6/analysis , Lonicera , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Mice , Mortality , Morus , Peptide Fragments/analysis , Prunus armeniaca , Respiration/drug effects , SARS-CoV-2 , Treatment Outcome , Tumor Necrosis Factor-alpha/analysis
6.
Mathematics ; 9(22):2849, 2021.
Article in English | MDPI | ID: covidwho-1512483

ABSTRACT

At the end of 2019, an outbreak of the novel coronavirus (COVID-19) made a profound impact on the country’s production and people’s daily lives. Up until now, COVID-19 has not been fully controlled all over the world. Based on the clinical research progress of infectious diseases, combined with epidemiological theories and possible disease control measures, this paper establishes a Susceptible Infected Recovered (SIR) model that meets the characteristics of the transmission of the new coronavirus, using the least square estimation (LSE) method to estimate the model parameters. The simulation results show that quarantine and containment measures as well as vaccine and drug development measures can control the spread of the epidemic effectively. As can be seen from the prediction results of the model, the simulation results of the epidemic development of the whole country and Nanjing are in agreement with the real situation of the epidemic, and the number of confirmed cases is close to the real value. At the same time, the model’s prediction of the prevention effect and control measures have shed new light on epidemic prevention and control.

7.
Anesthesiology ; 135(6): 1076-1090, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1507118

ABSTRACT

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Illness/mortality , Critical Illness/therapy , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anticoagulants/administration & dosage , Antiviral Agents/administration & dosage , Cohort Studies , Factor Xa Inhibitors/administration & dosage , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Treatment Outcome
8.
Zhongguo Huanjing Kexue = China Environmental Science ; 41(8):3927, 2021.
Article in English | ProQuest Central | ID: covidwho-1498172

ABSTRACT

Based on the meteorological forecast data from the National Meteorological Bureau, this study developed an AERMOD-based pollution forecasting model for iron and steel plants, simulated air quality impacts of a typical iron and steel plant located in Hebei Province during the controlled period(from February to March in 2020) and the uncontrolled period(from April to October in 2020) of the COVID-19 epidemic, and validated the model with real monitoring air quality data. In case of adverse wind direction, the results showed that the average contribution of SO2, NOx and PM10 from the plant to three state-controlled monitoring stations were 20.19~33.81%, 17.49~23.46% and 2.02~2.69% respectively during the controlled period, and 13.43~21.01%, 11.09~20.92% and 1.20~2.22% during the uncontrolled period. The correlation coefficients between the forecast values of SO2, NOx and PM10 emission of the plant and the real monitoring values of the three state-controlled monitoring stations were higher in the controlled period(the highest values are 0.43,0.48 and 0.29, respectively, at individual monitoring station) compared with the uncontrolled period(the highest values are 0.42,0.39 and 0.07, respectively) due to the less interference from other anthropogenic emission sources during the controlled period.

9.
iScience ; 24(10): 103213, 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1446745

ABSTRACT

The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 µM. 6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro domain in vitro. We therefore propose that 6-TG is a direct-acting antiviral that could potentially be repurposed and incorporated into the set of treatment and prevention options for COVID-19.

11.
World J Gastroenterol ; 27(32): 5404-5423, 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1379993

ABSTRACT

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.


Subject(s)
/pharmacology , Intestines , Reperfusion Injury , Caco-2 Cells , Human Umbilical Vein Endothelial Cells , Humans , Intestinal Mucosa , Recombinant Proteins/pharmacology , Reperfusion Injury/prevention & control
12.
Transp Res Interdiscip Perspect ; 11: 100450, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1364500

ABSTRACT

During the COVID-19 crisis, a series of measures were taken to restrict travel and social activities outside the home in order to curb the pandemic and ameliorate its negative effects. These unprecedented measures have had a profound impact on the number and purposes of trips and modes of travel. In China, although the pandemic is now generally under control and transport availability has returned to nearly normal, the extent of the changes in travel behaviour wrought during and after the pandemic still remains unclear. Therefore, the aim of this paper is to investigate the differences in individual travel behaviours during and after the COVID-19 pandemic, using Huzhou as an example. Semi-structured interviews were used to examine the influence of COVID-19 on the travel behaviour and perceptions of different groups. The results indicate that, initially, travel demand was greatly reduced. Second, decreased travel reduced participation in activities, which can have adverse effects on people's health as well as their subjective well-being. Third, the degree and duration of such impacts varied from person to person. Students, lower income cohorts, groups living in small communities with insufficient green spaces, and those working in tourism, catering, informal businesses and transport-related sectors were more vulnerable than others. Policymakers, urban and transport planners should therefore pay attention to the social inequities that arise from unequal access to transport and heterogeneity between individuals. Additionally, public transport systems require further development to promote social cohesion.

13.
Blood Purif ; 51(5): 410-416, 2022.
Article in English | MEDLINE | ID: covidwho-1362021

ABSTRACT

INTRODUCTION: Systematic inflammatory response occurred in some critically ill patients with COVID-19. Cytokine reduction by hemadsorption is a mechanism of treatment. However, whether CytoSorb hemoperfusion works for critically ill COVID-19 patients remains unknown. MATERIALS AND METHODS: We observed case series of critically ill COVID-19 patients receiving CytoSorb hemoperfusion as rescue therapy from 3 hospitals in Hubei, China from February 28, 2020, to April 7, 2020. Their demographic, laboratory, and clinical data were collected. The parameters for organ function and IL-6 levels were compared before and after treatments. RESULTS: A total of 10 cases were included. The median age of the patients was 67.7 years (range = 50-85) with APACHE II (23.5) and SOFA (11.4). Patients received a median of 3 attempts of hemoperfusion (range = 1-6). The median CytoSorb perfusion time was 47 h (12-92 h). The level of IL-6 significantly decreased after treatments (712.6 [145-5,000] vs. 136.7 [46.3-1,054] pg/mL, p = 0.005). Significant improvement was found in PaO2/FiO2 (118 [81-220] vs. 163 [41-340] mm Hg, p = 0.04) and lactate levels (2.5 [1-18] vs. 1.7 [1.1-10] mmol/L, p = 0.009). The hemodynamics measured by norepinephrine/MAP slightly improved after treatment (17 [0-68] vs. 8 [0-39], p = 0.09). Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. CONCLUSION: Treatment with CytoSorb in critically ill COVID-19 patients was associated with decreased IL-6 improvement in oxygenation. However, these effects cannot be confirmed as the direct effects of CytoSorb owing to lack of controls. Establishing causality requires large-scale randomized clinical trials.


Subject(s)
COVID-19 , Hemoperfusion , Aged , Aged, 80 and over , COVID-19/therapy , Critical Illness/therapy , Hemadsorption , Humans , Interleukin-6 , Middle Aged
14.
BMC Infect Dis ; 21(1): 693, 2021 Jul 20.
Article in English | MEDLINE | ID: covidwho-1318276

ABSTRACT

BACKGROUND: Nosocomial infections (NIs) are an important cause of mortality, and increasing evidence reveals that the prevalence of NIs can be reduced through effective prevention and control measures. The aim of this study was to investigate the impact of the prevention and control measures for the COVID-19 pandemic on NIs. METHODS: A retrospective study was conducted to analyze the prevalence of NIs before and after COVID-19 pandemic for 6 months in the Children's Hospital of Soochow University. RESULTS: A total of 39,914 patients in 2019 and 34,645 patients in 2020 were admitted to the hospital during the study. There were 1.39% (481/34645) of patients with NIs in 2020, which was significantly lower than the 2.56% (1021/39914) of patients in 2019. The rate of critical and fatal cases was also decreased. In addition, the rate of appropriate handwashing, the number of protective gloves and aprons used per person and the number of healthcare staff per patients were significantly increased. Except for the ICU, the prevalence of nosocomial infection in most departments decreased from 2019 to 2020. Regarding the source of infections, a significant reduction was mainly observed in respiratory (0.99% vs 0.42%, p = 0.000) and digestive tract (0.63% vs 0.14%, p = 0.000). The microorganism analysis of respiratory infections indicated an obvious decline in acinetobacters and fungi. The most significant decline of pathogens in gastrointestinal infections was observed for rotavirus. The comparison of catheter-related nosocomial infections between 2019 and 2020 did not show significant differences. CONCLUSIONS: The prevention and control measures for the COVID-19 pandemic have reduced the nosocomial infection in almost all departments, except the ICU, mainly regarding respiratory, gastrointestinal, and oral infections, while catheter-related infections did not show any differences.


Subject(s)
COVID-19/prevention & control , Cross Infection/epidemiology , SARS-CoV-2 , Adolescent , Child , Child, Hospitalized , Child, Preschool , China/epidemiology , Cross Infection/etiology , Female , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Infection Control , Male , Pandemics , Prevalence , Retrospective Studies , Tertiary Care Centers
16.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-3694

ABSTRACT

A review. Since the outbreak of COVID-19 in Wuhan in Dec. 2019, this epidemic has heavily threatened people′s health, bringing great panic to the public. This article reviews the data of investigation and research on infectious diseases of the 21st century, to provide information for effective psychol. aid in response to the current epidemic of COVID-19. The article discusses the significance of psychol. aid in previous public health incidents, and suggests the effective psychol. assistance provided to different populations during the current COVID-19 epidemic.

17.
Medicine (Baltimore) ; 99(44): e22847, 2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-998541

ABSTRACT

Numerous cases of pneumonia from a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China during December 2019.We determined the correlations of patient parameters with disease severity in patients with COVID-19.A total of 132 patients from Wuhan Fourth Hospital who had COVID-19 from February 1 to February 29 in 2020 were retrospectively analyzed.Ninety patients had mild disease, 32 had severe disease, and 10 had critical disease. The severe/critical group was older (P < .05), had a higher proportion of males (P < .05), and had a greater mortality rate (0% vs 61.9%, P < .05). The main symptoms were fever (n = 112, 84.8%) and cough (n = 96, 72.7%). Patients were treated with antiviral agents (n = 94, 71.2%), antibiotics (n = 92, 69.7%), glucocorticoids (n = 46, 34.8%), intravenous immunoglobulin (n = 38, 27.3%), and/or traditional Chinese medicine (n = 40, 30.3%). Patients in the severe/critical group received mechanical ventilation (n = 22, 16.7%) or high-flow nasal can-nula oxygen therapy (n = 6, 4.5%). Chest computed tomography (CT) indicated bilateral pneumonia in all patients. Relative to the mild group, the severe/critical group had higher levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, B-type natriuretic peptide (BNP), liver enzymes, and myocardial enzymes (P < .05), and decreased levels of lymphocytes and blood oxygen partial pressure (P < .05).The main clinical symptoms of patients from Wuhan who had COVID-19 were fever and cough. Patients with severe/critical disease were more likely to be male and elderly. Disease severity correlated with increased leukocytes, CRP, PCT, BNP, D-dimer, liver enzymes, and myocardial enzymes, and with decreased lymphocytes and blood oxygen partial pressure.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Retrospective Studies , SARS-CoV-2
19.
Chin J Integr Med ; 26(9): 648-655, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-648556

ABSTRACT

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Interferon-alpha/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Administration, Inhalation , Adult , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Integrative Medicine , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Risk Assessment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Severity of Illness Index , Survival Rate
20.
bioRxiv ; 2020 Jul 02.
Article in English | MEDLINE | ID: covidwho-635950

ABSTRACT

A recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG) inhibits SARS-CoV-2 PLpro-catalyzed viral polyprotein cleavage and ISG15 deconjugation in cells and inhibits replication of SARS-CoV-2 in Vero-E6 cells and Calu3 cells at submicromolar levels. As a well-characterized FDA-approved orally delivered drug, 6-TG represents a promising therapeutic for COVID-19 and other emerging coronaviruses. ONE SENTENCE SUMMARY: A repurposed drug that targets an essential enzymatic activity of SARS-CoV-2 represents a promising COVID-19 therapeutic.

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