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1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
J Evid Based Med ; 14(4): 313-332, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1462829

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , China , Humans , Medicine, Chinese Traditional , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
3.
Nat Med ; 26(9): 1491-1493, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1286464

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

4.
J Med Virol ; 93(4): 2505-2512, 2021 04.
Article in English | MEDLINE | ID: covidwho-1023298

ABSTRACT

To investigate the dynamic changes of Krebs von den Lungen-6 (KL-6) among patients with coronavirus disease 2019 (COVID-19) and the role of KL-6 as a noninvasive biomarker for predicting long-term lung injury, the clinical information and laboratory tests of 166 COVID-19 patients were collected, and a correlation analysis between KL-6 and other parameters was conducted. There were 17 (10.2%, 17/166) severe/critical and 149 (89.8%, 149/166) mild COVID-19 patients in our cohort. Serum KL-6 was significantly higher in severe/critical COVID-19 patients than in mild patients (median 898.0 vs. 451.2 U/ml, p < .001). KL-6 was next confirmed to be a sensitive and specific biomarker for distinguishing mild and severe/critical patients and correlate to computed tomography lung lesions areas. Serum KL-6 concentration during the follow-up period (>100 days postonset) was well correlated to those concentrations within 10 days postonset (Pearson r = .867, p < .001), indicating the prognostic value of KL-6 levels in predicting lung injury after discharge. Finally, elevated KL-6 was found to be significantly correlated to coagulation disorders, and T cells subsets dysfunctions. In summary, serum KL-6 is a biomarker for assessing COVID-19 severity and predicting the prognosis of lung injury of discharged patients.


Subject(s)
COVID-19/blood , Lung Injury/blood , Mucin-1/blood , Adult , Aged , Biomarkers/blood , COVID-19/diagnostic imaging , Female , Humans , Lung/diagnostic imaging , Lung/physiopathology , Lung Injury/diagnostic imaging , Lung Injury/physiopathology , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Tomography, X-Ray Computed/methods
5.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-3966

ABSTRACT

The present study analyzes the clin. effect of traditional Chinese medicine (TCM) Toujie Quwen granules in the early curative effect and the related inflammatory index expression of the COVID-19. The clin. syndrome and inflammatory particles of COVID-19 can be alleviated by early and timely use of Toujie Quwen granules.

6.
China Tropical Medicine ; 20(8):746-750, 2020.
Article in Chinese | GIM | ID: covidwho-860911

ABSTRACT

Objective: To explore the clinical effect of "Feiyan Yihao" Chinese medicine granules in the treatment of cases of COVID-19.

7.
Cell Mol Immunol ; 17(11): 1119-1125, 2020 11.
Article in English | MEDLINE | ID: covidwho-841899

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.


Subject(s)
Betacoronavirus/physiology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Gastrointestinal Tract/virology , Pneumonia, Viral/diagnosis , Antibodies, Viral/metabolism , COVID-19 , COVID-19 Testing , Coronavirus Infections/immunology , Epitopes/immunology , Humans , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Pandemics , Pneumonia, Viral/immunology , Protein Binding , Protein Domains/immunology , SARS-CoV-2 , Serologic Tests , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Virus Shedding
8.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1013

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) is wreaking havoc throughout the world. However, we know little about the virus load and changes of laboratory i

9.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-849

ABSTRACT

A novel coronavirus (SARS-CoV-2) was identified in December 2019, Wuhan, China. This new coronavirus has resulted in numerous cases of Coronavirus Disease 2019

10.
BioData Min ; 13: 15, 2020.
Article in English | MEDLINE | ID: covidwho-792331

ABSTRACT

BACKGROUND: Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. METHODS: TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a "drug-active ingredient-potential target" network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. RESULTS: A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of "drug-component-target-biological process-signaling pathway". Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. CONCLUSIONS: Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

11.
Cell Death Discov ; 6: 76, 2020.
Article in English | MEDLINE | ID: covidwho-707616

ABSTRACT

SARS-CoV-2 has resulted in numerous cases of Coronavirus Disease 2019 (COVID-19) worldwide. In addition to fever and respiratory symptoms, digestive symptoms also are observed in some patients with COVID-19. Angiotensin-converting enzyme 2 (ACE2) was reported to be the receptor for SARS-CoV-2. The aim of this study was to comprehensively investigate the digestive symptoms that occur in COVID-19 patients, and the potential pathogenic route of the SARS-CoV-2 infection in digestive tract organs (from the oral cavity to the gastrointestinal tract). We investigated the digestive symptoms of 48 patients with COVID-19 and explored ACE2 expression in digestive tract and lung cancers, based on a series of bulk and single-cell RNA sequencing data obtained from public databases. We found that 25% (12/48) of the patients with COVID-19 suffered from digestive symptoms, among which pharyngalgia (7/48) was the most common manifestation, followed by diarrhea (3/48), anorexia (3/48), and nausea (1/48). The bulk tissue RNA sequencing analysis indicated that digestive tract organs had higher ACE2 expression levels compared to the lung, and the expression of ACE2 in the lung increased with age. Single-cell RNA-Seq results showed that the ACE2-positive-cell ratio in digestive tract organs was significantly higher compared to the lung. ACE2 expression was higher in tumor cells compared to normal control (NC) tissues. While in gastric tissues, ACE2 expression gradually increased from chronic gastritis to metaplasia, to early cancer. Our data might provide a theoretical basis for screening the SARS-CoV-2 susceptible population and for the clinical classification of treatment of patients with COVID-19.

12.
Nat Med ; 26(5): 672-675, 2020 05.
Article in English | MEDLINE | ID: covidwho-65153

ABSTRACT

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Virus Shedding , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
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