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1.
Acta Pharmacol Sin ; 2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1209738

ABSTRACT

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

2.
World J Gastroenterol ; 27(9): 835-853, 2021 Mar 07.
Article in English | MEDLINE | ID: covidwho-1138767

ABSTRACT

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.


Subject(s)
/complications , Liver Diseases/virology , Adult , Aged , Aged, 80 and over , /physiopathology , China/epidemiology , Female , Follow-Up Studies , Humans , Liver Diseases/diagnosis , Liver Diseases/mortality , Liver Diseases/physiopathology , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis
3.
Signal Transduct Target Ther ; 6(1): 123, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1135650

ABSTRACT

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.


Subject(s)
Immunity, Innate , Membrane Proteins/immunology , Nucleotidyltransferases/immunology , RNA, Viral/immunology , Signal Transduction/immunology , Viral Proteins/immunology , A549 Cells , Animals , Chickens , HEK293 Cells , HeLa Cells , Humans , Ligases/immunology , Mice
4.
JMIR Med Inform ; 9(2): e24572, 2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1083499

ABSTRACT

BACKGROUND: COVID-19 has overwhelmed health systems worldwide. It is important to identify severe cases as early as possible, such that resources can be mobilized and treatment can be escalated. OBJECTIVE: This study aims to develop a machine learning approach for automated severity assessment of COVID-19 based on clinical and imaging data. METHODS: Clinical data-including demographics, signs, symptoms, comorbidities, and blood test results-and chest computed tomography scans of 346 patients from 2 hospitals in the Hubei Province, China, were used to develop machine learning models for automated severity assessment in diagnosed COVID-19 cases. We compared the predictive power of the clinical and imaging data from multiple machine learning models and further explored the use of four oversampling methods to address the imbalanced classification issue. Features with the highest predictive power were identified using the Shapley Additive Explanations framework. RESULTS: Imaging features had the strongest impact on the model output, while a combination of clinical and imaging features yielded the best performance overall. The identified predictive features were consistent with those reported previously. Although oversampling yielded mixed results, it achieved the best model performance in our study. Logistic regression models differentiating between mild and severe cases achieved the best performance for clinical features (area under the curve [AUC] 0.848; sensitivity 0.455; specificity 0.906), imaging features (AUC 0.926; sensitivity 0.818; specificity 0.901), and a combination of clinical and imaging features (AUC 0.950; sensitivity 0.764; specificity 0.919). The synthetic minority oversampling method further improved the performance of the model using combined features (AUC 0.960; sensitivity 0.845; specificity 0.929). CONCLUSIONS: Clinical and imaging features can be used for automated severity assessment of COVID-19 and can potentially help triage patients with COVID-19 and prioritize care delivery to those at a higher risk of severe disease.

5.
Preprint | SciFinder | ID: ppcovidwho-5148

ABSTRACT

A review for summary of experience in prevention and control management of radiol department under the background of 2019-nCoV infection

6.
Front Oncol ; 10: 1272, 2020.
Article in English | MEDLINE | ID: covidwho-853981

ABSTRACT

Background: A recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which began in Wuhan, China, with a high level of human-to-human transmission has been reported. There are limited data available on Coronavirus Disease 2019 (COVID-19) patients with hematological malignancies with more than 60 days of follow-up. This study describes the clinical characteristics, including multiple recurrences of COVID-19, in a patient with chronic lymphocytic leukemia (CLL) during 69 days of follow-up. Case Presentation: A 72-year-old female was admitted to hospital isolation after being infected with COVID-19 as part of a family cluster on January 30, 2020. Apart from SARS-Cov-2 virus infection, laboratory results revealed lymphocytosis of uncertain etiology and abnormal distribution of T lymphocytes. On blood smears, small blue lymphocytes with scant cytoplasm were observed, and the presence of high levels of circulating clonal B cells was also demonstrated by flow cytometry. The patient was diagnosed with COVID-19 and CLL. Among her family members, she had the highest viral loads and the fastest progression on lung injury and developed severe pneumonia. Serological results showed she had both 2019-nCoV-specific IgM and IgG antibodies; however, only IgG antibodies were detected in her husband's plasma. Results: A combination regimen of antiviral therapy and high-dose intravenous immunoglobulin (IVIG) in the early stage seemed to be effective for treating CLL and SARS-Cov-2 infection. Because of the low humoral immune response, the CLL patient could not effectively clear the SARS-Cov-2 infection and suffered from recurrence twice during the 69-day follow-up. Conclusion: In CLL, a neoplastic antigen-specific B-cell clone proliferates, and the progeny cells accumulate and outgrow other B cells, leading to immune deficiency. Considering the low humoral immune response and ineffective clearance of SARS-Cov-2 in CLL patients, the follow-up and home quarantine period should be extended. We need further studies to clarify suspending or continuing CLL therapy during COVID infection. For those patients who are prone to progression to severe disease, administering humoral immunity therapies can help to prevent disease progression and quickly meet the cure criteria.

7.
Chin Med ; 15: 102, 2020.
Article in English | MEDLINE | ID: covidwho-797649

ABSTRACT

Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

8.
Front Public Health ; 8: 152, 2020.
Article in English | MEDLINE | ID: covidwho-269289

ABSTRACT

Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

9.
Preprint | medRxiv | ID: ppmedrxiv-20058040

ABSTRACT

BackgroundConcomitance with diabetes is associated with high mortality in critical conditions. Patients with previous diabetes are more vulnerable to COVID-19. However, new-onset COVID-19-related diabetes (CRD) and its relevance have scarcely been reported. This study investigates new-onset CRD and its correlation with poor outcomes or death in patients with COVID-19. MethodsWe performed a single center, retrospective case series study in 120 patients with laboratory confirmed COVID-19 at a university hospital. Fasting blood glucose (FBG) [≥]7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as CRD. The Critical status was defined as admitted to intensive care unit (ICU) or death. ResultsAfter excluding patients with a history of diabetes, chronic heart, kidney, and liver disease, 69 patients with COVID-19 were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). The prevalence of CRD in Critical and Moderate+Severe patients was 53.85% and 13.95%, respectively. Kaplan-Meier survival analysis revealed a significantly higher mortality rate in patients with CRD (P=0.0019). Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Cluster analysis suggested that indicators for multi-organ injury were interdependent, and more proximities of FBG with indicators for multi-organ injury was present. ConclusionOur results suggest that new onset COVID-19-related diabetes is an indicator of multi-organ injury and predictor for poor outcomes and death in COVID- 19 patients. As it is easy to perform for clinical practices and even self-monitoring, glucose testing will be much helpful for predicting poor outcomes to facilitate appropriate intensive care in patients with COVID-19. FundingNational Key Research and Development Program of China; The Beijing Science and Technology Project. Significance of this studyO_ST_ABSEvidence before this studyC_ST_ABSConcomitance with diabetes is associated with high mortality in critical conditions. Patients with previous diabetes are more vulnerable to COVID-19. However, new-onset COVID-19-related diabetes (CRD) and its relevance have scarcely been reported. Recently, an international group of leading diabetes researchers participating in the CoviDIAB Project have established a global registry of patients with Covid-19-related diabetes (covidiab.e-dendrite.com). Added value of this study?New-onset diabetes in COVID-19 defined as CRD was investigated. Correlation between CRD and poor outcomes or death in patients with COVID-19 was found. About half of the Critical patients have new onset CRD. CRD is the representative of the clustered indicators of multi-organ injury and is the predictor for poor outcomes and death. How might these results change the focus of research or clinical practice?Our results suggest that new onset diabetes is an indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. The study of CRD may also uncover novel mechanisms of disease.

10.
Preprint | medRxiv | ID: ppmedrxiv-20026864

ABSTRACT

ImportanceThe recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago. ObjectiveWe aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and ParticipantsWe extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and MeasuresSeverity and mortality. ResultsOlder age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age ([≥]65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P<0.001) and SARS (37.4 vs. 4.9, P<0.001). In the case series, men tend to be more serious than women (P=0.035), although age was comparable between men and women. In the public data set, age was also comparable between men and women in the deceased group or the survived group in patients with COVID-19. Meanwhile, gender distribution was exactly symmetrical in the 1019 survivors of COVID-19. However, the percentage of male were higher in the deceased group than in the survived group (70.3 vs. 50.0, P=0.015). The gender role in mortality was also observed in SARS patients. Survival analysis showed that men (hazard ratio [95% CI] 1.47 [1.05-2.06, P= 0.025) had a significantly higher mortality rate than women in patients with SARS. Conclusions and RelevanceOlder age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility. Key PointsO_ST_ABSQuestionC_ST_ABSAre men more susceptible to getting and dying from COVID-19? FindingsIn the case series, men tend to be more serious than women. In the public data set, the percentage of men were higher in the deceased group than in the survived group, although age was comparable between men and women. MeaningMale gender is a risk factor for worse outcome in patients with COVID independent of age and susceptibility.

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