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1.
Preprint in English | EuropePMC | ID: ppcovidwho-291513

ABSTRACT

Background: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset. The potential risk factors were also explored.Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients’ health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed.Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from posttraumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females compared with males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity.Interpretation: 15-month follow-up in this study aroused the need of extended rehabilitation intervention for complete recovery in COVID-19 patients. Funding: None to declare. Declaration of Interest: All the authors declare no competing interests.Ethical Approval: The Research Ethics Committee of Shanghai Changzheng Hospital approved this study (2020SL007).

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1582-1588, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1464140

ABSTRACT

AbstractObjective: To analyze the liver injury and coagulation dysfunction in COVID-19 severe/critical type patients. METHODS: The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test. RESULTS: Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27-80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05). CONCLUSION: In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Aged , Aged, 80 and over , Female , Humans , Liver , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
5.
Nat Struct Mol Biol ; 28(9): 755-761, 2021 09.
Article in English | MEDLINE | ID: covidwho-1406396

ABSTRACT

Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg10-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg10-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19.


Subject(s)
Bradykinin/metabolism , COVID-19/pathology , Kallidin/metabolism , Receptors, Bradykinin/metabolism , Cryoelectron Microscopy , Enzyme Activation/physiology , Humans , Protein Structure, Tertiary , Pulmonary Edema/pathology , Pulmonary Edema/virology , SARS-CoV-2
6.
Epidemiologia ; 2(2):207-226, 2021.
Article in English | MDPI | ID: covidwho-1259455

ABSTRACT

The COVID-19 pandemic has placed an unprecedented burden on public health and strained the worldwide economy. The rapid spread of COVID-19 has been predominantly driven by aerosol transmission, and scientific research supports the use of face masks to reduce transmission. However, a systematic and quantitative understanding of how face masks reduce disease transmission is still lacking. We used epidemic data from the Diamond Princess cruise ship to calibrate a transmission model in a high-risk setting and derive the reproductive number for the model. We explain how the terms in the reproductive number reflect the contributions of the different infectious states to the spread of the infection. We used that model to compare the infection spread within a homogeneously mixed population for different types of masks, the timing of mask policy, and compliance of wearing masks. Our results suggest substantial reductions in epidemic size and mortality rate provided by at least 75% of people wearing masks (robust for different mask types). We also evaluated the timing of the mask implementation. We illustrate how ample compliance with moderate-quality masks at the start of an epidemic attained similar mortality reductions to less compliance and the use of high-quality masks after the epidemic took off. We observed that a critical mass of 84% of the population wearing masks can completely stop the spread of the disease. These results highlight the significance of a large fraction of the population needing to wear face masks to effectively reduce the spread of the epidemic. The simulations show that early implementation of mask policy using moderate-quality masks is more effective than a later implementation with high-quality masks. These findings may inform public health mask-use policies for an infectious respiratory disease outbreak (such as one of COVID-19) in high-risk settings.

7.
J Med Internet Res ; 23(5): e26883, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1229125

ABSTRACT

BACKGROUND: The prevalence of depressive and anxiety symptoms in patients with COVID-19 is higher than usual. Previous studies have shown that there are drug-to-drug interactions between antiretroviral drugs and antidepressants. Therefore, an effective and safe treatment method was needed. Cognitive behavioral therapy (CBT) is the first-line psychological therapy in clinical treatment. Computerized CBT (cCBT) was proven to be an effective alternative to CBT and does not require face-to-face therapy between a therapist and the patient, which suited the COVID-19 pandemic response. OBJECTIVE: This study aims to evaluate the efficacy of the cCBT program we developed in improving depressive and anxiety symptoms among patients with COVID-19. METHODS: We customized a cCBT program focused on improving depressive and anxiety symptoms among patients with COVID-19, and then, we assessed its effectiveness. Screening was based on symptoms of depression or anxiety for patients who scored ≥7 on the Hamilton Depression Rating Scale (HAMD17) or the Hamilton Anxiety Scale (HAMA). A total of 252 patients with COVID-19 at five sites were randomized into two groups: cCBT + treatment as usual (TAU; n=126) and TAU without cCBT (n=126). The cCBT + TAU group received the cCBT intervention program for 1 week. The primary efficacy measures were the HAMD17 and HAMA scores. The secondary outcome measures were the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Athens Insomnia Scale (AIS). Assessments were carried out pre- and postintervention. The patients' symptoms of anxiety and depression in one of the centers were assessed again within 1 month after the postintervention assessment. RESULTS: The cCBT + TAU group displayed a significantly decreased score on the HAMD17, HAMA, SDS, SAS, and AIS after the intervention compared to the TAU group (all P<.001). A mixed-effects repeated measures model revealed significant improvement in symptoms of depression (HAMD17 and SDS scores, both P<.001), anxiety (HAMA and SAS scores, both P<.001), and insomnia (AIS score, P=.002) during the postintervention and follow-up periods in the cCBT + TAU group. Additionally, the improvement of insomnia among females (P=.14) and those with middle school education (P=.48) in the cCBT + TAU group showed no significant differences when compared to the TAU group. CONCLUSIONS: The findings of this study suggest that the cCBT program we developed was an effective nonpharmacological treatment for symptoms of anxiety, depression, and insomnia among patients with COVID-19. Further research is warranted to investigate the long-term effects of cCBT for symptoms of anxiety, depression, and insomnia in patients with COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030084; http://www.chictr.org.cn/showprojen.aspx?proj=49952.


Subject(s)
Anxiety/therapy , COVID-19/psychology , Cognitive Behavioral Therapy/methods , Depression/therapy , Adult , Female , Humans , Male , Pandemics , Prospective Studies , SARS-CoV-2/isolation & purification
8.
BMJ Case Rep ; 14(4)2021 Apr 21.
Article in English | MEDLINE | ID: covidwho-1197249

ABSTRACT

A 35-year-old Hispanic man presented with fever, chills, dysuria, diarrhoea, scleral icterus, tachycardia and tachypnea. He was found to be COVID-19 positive, CT of the pelvis revealed prostatic abscess, and urine culture grew Klebsiella pneumoniae Additionally, he was found to have diabetes and cirrhosis. During treatment, the patient developed vision loss, and was diagnosed with endogenous Klebsiella endophthalmitis. The patient was treated with intravenous antibiotics, pars plana vitrectomy, intravitreal antibiotics and cystoscopy/suprapubic catheter placement. On follow-up, the patient has had the suprapubic catheter removed, and successfully passed a voiding trial, but suffers permanent vision loss in both eyes.


Subject(s)
COVID-19 , Diabetes Mellitus , Endophthalmitis , Klebsiella Infections , Prostatitis , Adult , Anti-Bacterial Agents/therapeutic use , Blindness , COVID-19/complications , Diabetes Mellitus/virology , Endophthalmitis/complications , Endophthalmitis/diagnosis , Endophthalmitis/therapy , Humans , Klebsiella Infections/complications , Klebsiella Infections/diagnosis , Klebsiella Infections/drug therapy , Klebsiella pneumoniae , Liver Cirrhosis/complications , Liver Cirrhosis/virology , Male , Prostatitis/complications , Prostatitis/microbiology , SARS-CoV-2 , Vitrectomy
9.
Biochem Biophys Res Commun ; 538: 47-53, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-1124962

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global pandemic. Although great efforts have been made to develop effective therapeutic interventions, only the nucleotide analog remdesivir was approved for emergency use against COVID-19. Remdesivir targets the RNA-dependent RNA polymerase (RdRp), an essential enzyme for viral RNA replication and a promising drug target for COVID-19. Recently, several structures of RdRp in complex with substrate RNA and remdesivir were reported, providing insights into the mechanisms of RNA recognition by RdRp. These structures also reveal the mechanism of RdRp inhibition by nucleotide inhibitors and offer a molecular template for the development of RdRp-targeting drugs. This review discusses the recognition mechanism of RNA and nucleotide inhibitor by RdRp, and its implication in drug discovery.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Discovery , Nucleic Acid Synthesis Inhibitors/pharmacology , SARS-CoV-2/drug effects , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/pharmacology , Alanine/chemistry , Alanine/pharmacology , Antiviral Agents/chemistry , Catalytic Domain , Coronavirus RNA-Dependent RNA Polymerase , Humans , Nucleic Acid Synthesis Inhibitors/chemistry , Protein Conformation , RNA, Viral/biosynthesis , SARS-CoV-2/enzymology , SARS-CoV-2/genetics , Virus Replication/drug effects
10.
Nat Struct Mol Biol ; 28(3): 319-325, 2021 03.
Article in English | MEDLINE | ID: covidwho-1118814

ABSTRACT

The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Enzyme Inhibitors/pharmacology , Suramin/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Binding Sites , Catalytic Domain , Chlorocebus aethiops , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cryoelectron Microscopy , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Protein Conformation , RNA, Viral/chemistry , RNA, Viral/metabolism , SARS-CoV-2/drug effects , Suramin/chemistry , Suramin/metabolism , Vero Cells , Virus Replication/drug effects
11.
Biophysical Journal ; 120(3, Supplement 1):263a, 2021.
Article in English | ScienceDirect | ID: covidwho-1080239
12.
Results Phys ; 22: 103881, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1062584

ABSTRACT

Objective: It aimed to analyze the epidemic situation of new coronary pneumonia (COVID-19) based on the epidemiological Markov model, and to study the clinical risk factors of the patients based on the patient's cardinal data and clinical symptoms. Methods: A total of 500 patients with COVID-19 diagnosed by nucleic acid testing in the X hospital from January 2020 to May 2020 were collected. According to the severity of the disease, they were classified into general group (200 cases) and acute critical group (300 cases). Markov model to predict the number of COVID-19 infections was constructed. Patient's general information, clinical characteristics, and prevention methods were analyzed. Results: According to Markov model statistics, the developmental expected stay time of patients infected with COVID-19 was 14 days. 2. The two groups of patients had statistically considerable differences in complications such as gender, age, hypertension, coronary heart disease, shortness of breath, myocardial damage, and thrombocytopenia (P < 0.05). 3. Logistic multivariate regression analysis showed that the clinical risk factors for patients with COVID-19 mainly included the patient's gender, age, whether they were associated with hypertension, coronary heart disease, shortness of breath, myocardial damage, and thrombocytopenia. Conclusion: Markov model can be utilized to judge the time course of the COVID-19 in various development states. In addition, the COVID-19 spread rapidly and is extremely harmful. Clinically, through active prevention, the treatment effect can be improved, the patient's respiratory function, and the quality of life can also be improved.

13.
Sci Rep ; 10(1): 22369, 2020 12 22.
Article in English | MEDLINE | ID: covidwho-997944

ABSTRACT

We aimed to analyse clinical characteristics and identify risk factors predicting all-cause mortality in older patients with severe coronavirus disease 2019 (COVID-19). A total of 281 older patients with severe COVID-19 were categorized into two age groups (60-79 years and ≥ 80 years). Epidemiological, clinical, and laboratory data, and outcome were obtained. Patients aged ≥ 80 years had higher mortality (63.6%) than those aged 60-79 years (33.5%). Anorexia and comorbidities including hypertension, diabetes and COPD, higher levels of lactate dehydrogenase (LDH), osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I and procalcitonin, and higher SOFA scores were more common in patients aged > 80 years than those aged 60-79 years and also more common and higher in non-survivors than survivors. LDH, osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I, and procalcitonin were positively correlated with age and sequential organ failure assessment (SOFA), whereas CD8+ and lymphocyte counts were negatively correlated with age and SOFA. Anorexia, comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease (COPD), LDH, osmotic pressure, and SOFA were significantly associated with 28-day all-cause mortality. LDH, osmotic pressure and SOFA were valuable for predicting 28-day all-cause mortality, whereas the area under the receiver operating characteristic curve of LDH was the largest, with sensitivity of 86.0% and specificity of 80.8%. Therefore, patients with severe COVID-19 aged ≥ 80 years had worse condition and higher mortality than did those aged 60-79 years, and anorexia and comorbidities including hypertension, diabetes, COPD, elevated plasma osmotic pressure, LDH, and high SOFA were independent risk factors associated with 28-day all-cause mortality in older patients with severe COVID-19. LDH may have the highest predictive value for 28-day all-cause mortality in all examined factors.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Organ Dysfunction Scores , SARS-CoV-2/genetics , Age Factors , Aged , Aged, 80 and over , Anorexia , CD4-CD8 Ratio , COVID-19/blood , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors
14.
Med Sci Monit ; 26: e928861, 2020 Dec 14.
Article in English | MEDLINE | ID: covidwho-976582

ABSTRACT

BACKGROUND Rhinovirus (RV) is the most common pathogen involved in asthma, and COVID-19, caused by SARS-COV-2, may be more severe in asthma patients. Here, we applied integrated bioinformatics to identify potential key genes and cytokine pathways after RV infection in asthma, and analyzed changes in angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-COV-2. MATERIAL AND METHODS The gene expression profile dataset GSE149273 was downloaded from NCBI-GEO, which included 90 samples of non-infected, RVA, and RVC. Differentially expressed genes (DEGs) were identified using t tests in the limma R package, and subsequently investigated by GO, KEGG, and DO analysis. Moreover, the expression of ACE2 and the proportion of immune cells were further analyzed to determine the effects of RV on cytokines. RESULTS A total of 555 DEGs of RVA and 421 of RVC were identified. There were 415 DEGs in RVA and RVC, of which 406 were upregulated and 9 were downregulated. The functional enrichment analysis showed that most DEGs were obviously enriched in cytokines, and were mainly enriched in "influenza" and "hepatitis C, chronic". In addition, the expression of ACE2 increased significantly and the proportion of immune cytokines significantly changed after RV infection. Our results suggest that RV can activate the cytokine pathway associated with COVID-19 by increasing ACE2. CONCLUSIONS The DEGs and related cytokine pathways after asthma RV infection identified using integrated bioinformatics in this study elucidate the potential link between RV and COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Asthma/immunology , COVID-19/immunology , Cytokines/metabolism , Picornaviridae Infections/immunology , Protein Interaction Maps/genetics , Asthma/complications , COVID-19/genetics , COVID-19/virology , Computational Biology , Datasets as Topic , Gene Expression Profiling , Gene Expression Regulation/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Picornaviridae Infections/genetics , Protein Interaction Maps/immunology , Rhinovirus/immunology , SARS-CoV-2/immunology , Signal Transduction/genetics , Signal Transduction/immunology
15.
Ann Transl Med ; 8(18): 1158, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-875041

ABSTRACT

Background: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia. Methods: Seventy-two patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features. Results: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in 16 patients (22.22%), and in both lungs with "white lung" manifestations in 4 patients (5.56%). Subpleural multifocal consolidation was a predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18 patients, 8 of whom had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), and was mild and randomly distributed. In addition, both lungs of 28 patients had 2 or 3 CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage, and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05). Conclusions: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia.

16.
Nat Commun ; 11(1): 4968, 2020 10 02.
Article in English | MEDLINE | ID: covidwho-811573

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Subject(s)
Coronavirus Infections/diagnosis , Disease Progression , Pneumonia, Viral/diagnosis , Pneumonia , Tomography, X-Ray Computed/methods , Adult , Betacoronavirus , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques , Coinfection , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Female , Hospitalization , Humans , Lung/diagnostic imaging , Lung/pathology , Lymphocytes , Male , Middle Aged , Neutrophils , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Regression Analysis , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2
17.
Mol Ther Methods Clin Dev ; 18: 367-375, 2020 Sep 11.
Article in English | MEDLINE | ID: covidwho-644785

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.

18.
Chin Med ; 15: 46, 2020.
Article in English | MEDLINE | ID: covidwho-245698

ABSTRACT

Background: Dendrobii Officinalis Caulis (DC) is a well-known tonic herbal medicine worldwide and has favorable immunomodulatory activity. Various material specifications of DC are available in herbal markets, and DC is ingested by different edible methods. However, whether these specifications and edible methods are suitable or not remains unknown. Methods: In this study, we evaluated the suitability of four material specifications (fresh stem, dried stem, fengdou and powder) and three edible methods (making tea, soup and medicinal liquor) based on holistic polysaccharide marker (HPM), the major polysaccharide components in DC. First, the HPMs were extracted from the four specifications of DC by the three edible methods in different conditions. Second, qualitative and quantitative characterization of the extracted HPMs was performed using high performance gel permeation chromatography (HPGPC). Third, immunomodulatory activities of the extracted HPMs were evaluated in vivo. Results: The results showed that the HPMs were found to be quantitatively different from various specification of DC and edible methods. In vivo analysis indicated that the HPMs exerted positive effects on innate immune responses by increment in proliferation of splenocytes, secretion of IL-2 and cytotoxicity activity of NK cells. Moreover, the dosage amount of HPM should be defined as a certain range, but not the larger the better, for exerting strong immunological activities. Conclusion: According to the both chemical and biological results, fengdou by boiling with water for 4 h is the most recommended specification and edible method for DC.

19.
Science ; 368(6498): 1499-1504, 2020 06 26.
Article in English | MEDLINE | ID: covidwho-154668

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/chemistry , Betacoronavirus/enzymology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/chemistry , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/pharmacology , Alanine/chemistry , Alanine/metabolism , Alanine/pharmacology , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/physiology , Catalytic Domain , Coronavirus RNA-Dependent RNA Polymerase , Cryoelectron Microscopy , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Models, Molecular , Multiprotein Complexes/chemistry , Protein Conformation , RNA, Viral/chemistry , RNA, Viral/metabolism , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2 , Viral Nonstructural Proteins/metabolism , Virus Replication
20.
World J Pediatr ; 16(3): 232-239, 2020 06.
Article in English | MEDLINE | ID: covidwho-116370

ABSTRACT

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Child , Consensus , Humans , SARS-CoV-2
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