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1.
Anal Chem ; 2020 Jul 17.
Article in English | MEDLINE | ID: covidwho-661160

ABSTRACT

The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported worldwide by the end of May 2020. A rush to find the cure prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a pre-mium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical ele-ment of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, mak-ing them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation tech-nique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular model-ing also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pen-tasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the pres-ence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the posi-tive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic infor-mation on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of na-tive MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.

2.
Obesity (Silver Spring) ; 2020 Jul 17.
Article in English | MEDLINE | ID: covidwho-654908

ABSTRACT

OBJECTS: To assess the association between adipose tissue distribution and severity of clinical course in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: For this retrospective study, 143 hospitalized patients with confirmed coronavirus disease 2019(COVID-19) who underwent un-enhanced abdominal computed tomography (CT) scan between January 1th , 2020 and March 30th , 2020 were included. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with the severity of COVID-19 infection. RESULTS: There were 45 patients who were identified as critically ill. High visceral to subcutaneous adipose tissue area ratio (VSR, called visceral adiposity) (OR: 2.47, 95CI: 1.05 to 5.98, p=0.040) and low mean attenuation of skeletal muscle (SMD, called high intramuscular fat [IMF] deposition) (OR: 11.90, 95CI: 4.50 to 36.14, p<0.001) were independent risk factors for critical illness. Furthermore, visceral adiposity or high IMF deposition increased the risk of mechanical ventilation (p=0.013, p<0.001; respectively). High IMF deposition increased the risk of death (p=0.012). CONCLUSION: COVID-19 patients with visceral adiposity or high IMF deposition have higher risk for critical illness. Hence, patients with abdominal obesity should be monitored more carefully when hospitalized.

3.
Eur J Dent Educ ; 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-639370

ABSTRACT

INTRODUCTION: This study aimed to assess live online dental continuing education during COVID-19 epidemic in China. METHODS: Twenty-one institutions providing live online dental courses in China during COVID-19 epidemic enrolled in this study. Their online and/or offline course provision before and during the epidemic was retrospectively inquired. If live online education was provided, the number of courses, duration and number of participants per week were further investigated. Time distributions of live online dental courses were recorded and classified as within working time and out of working time. The test period of COVID-19 epidemic was for two weeks between 16 February and 29 February 2020. The control period of pre-COVID-19 epidemic was for ten weeks between 01 November 2019 and 09 January 2020. RESULTS: The percentages of offline and online courses provided by 21 dental continuing education institutions before COVID-19 epidemic were 95.2% (20 out of 21) and 28.6% (6 out of 21), respectively. All the institutions suspended offline courses whilst providing two live online courses, on average, per week with 188 minutes duration and 7290 participants during the epidemic. The total number of online courses for 10 weeks before the epidemic was 33, and that for two weeks during the epidemic was 119. The proportion of courses provided within working time raised from 6.1% (2 out of 33) of pre-COVID-19 to 46.2% (55 out of 119) during COVID-19. There were significant differences between before and during the epidemic (P < .001). CONCLUSION: The dental continuing education transferred from offline to online dramatically, and live online dental continuing education increased significantly during COVID-19 epidemic in China.

4.
National Science Review ; 7(6):1003-1011, 2020.
Article | WHO COVID | ID: covidwho-635319

ABSTRACT

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19) We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals Seventeen cytokines were linked to 2019-nCoV loads Fifteen cytokines, namely M-CSF, IL-10, IFN-alpha 2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-gamma, IL-1 alpha, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized

7.
Lancet Infect Dis ; 2020 Jun 17.
Article in English | MEDLINE | ID: covidwho-601834

ABSTRACT

BACKGROUND: As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. METHODS: In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. FINDINGS: Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8-15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3-21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11-0·46]) and among adults aged 20-59 years (OR 0·64 [95% CI 0·43-0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27-1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41-0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49-0·74) when household was defined on the basis of close relatives. INTERPRETATION: SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. FUNDING: US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.

8.
BMJ ; 369: m2195, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-592014

ABSTRACT

OBJECTIVE: To examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19). DESIGN: Cross sectional study. SETTING: Four hospitals in Wuhan, China. PARTICIPANTS: 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing. MAIN OUTCOME MEASURES: Covid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples. RESULTS: The average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%). CONCLUSION: Before a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.


Subject(s)
Coronavirus Infections/prevention & control , Health Personnel , Infection Control/instrumentation , Pandemics/prevention & control , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/prevention & control , Adult , Betacoronavirus , China , Coronavirus Infections/diagnosis , Cross-Sectional Studies , Female , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intensive Care Units , Male , Middle Aged , Occupational Exposure/prevention & control , Pneumonia, Viral/diagnosis
9.
Australasian J. Ultrasound Med. ; 2020.
Article in English | ELSEVIER | ID: covidwho-592882

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (COVID 19) pandemic has placed an unprecedented challenge on health care systems across the globe. Rapid assessment of the cardiorespiratory function to monitor disease progression and guide treatment is essential. Therefore, we have designed the COVID-US: a simplified cardiopulmonary ultrasound approach to use in suspected and confirmed COVID 19 patients, to aid front-line health workers in their decision-making in a surge crisis.

11.
Radiology ; 295(3): 200463, 2020 06.
Article in English | MEDLINE | ID: covidwho-505873

ABSTRACT

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/virology , Pneumonia, Viral/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/virology , Lung Diseases/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Radiography, Thoracic/methods , Retrospective Studies , Tomography, X-Ray Computed/methods , Young Adult
12.
Australasian J. Ultrasound Med. ; 2(23): 103-110, 20200501.
Article in English | ELSEVIER | ID: covidwho-506604

ABSTRACT

ICU ultrasonography constitutes important part of modern car patient care. Current standards and practice of infection control and prevention are inadequate. This purpose of this document is to adapt and expand the 2017 Australasian Society for Ultrasound in Medicine (ASUM) and the Australasian College for Infection Prevention Control (ACIPC) guidelines on minimum standards for reprocessing/cleaning of ultrasound transducers to the specifics of intensive care medicine and provide advice to the ICU practitioners and health care administrators. It considers the medical, administrative, financial and practical controversies surrounding implementation, and addresses emerging issues of care for patients with confirmed or suspected Corona Virus Disease 2019 (COVID-19).

13.
Interdiscip Sci ; 2020 Jun 01.
Article in English | MEDLINE | ID: covidwho-459220

ABSTRACT

A novel coronavirus, called 2019-nCoV, was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. Although there are some drugs to treat 2019-nCoV, there is no proper scientific evidence about its activity on the virus. It is of high significance to develop a drug that can combat the virus effectively to save valuable human lives. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods such as deep learning to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In the present work, we first collected virus RNA sequences of 18 patients reported to have 2019-nCoV from the public domain database, translated the RNA into protein sequences, and performed multiple sequence alignment. After a careful literature survey and sequence analysis, 3C-like protease is considered to be a major therapeutic target and we built a protein 3D model of 3C-like protease using homology modeling. Relying on the structural model, we used a pipeline to perform large scale virtual screening by using a deep learning based method to accurately rank/identify protein-ligand interacting pairs developed recently in our group. Our model identified potential drugs for 2019-nCoV 3C-like protease by performing drug screening against four chemical compound databases (Chimdiv, Targetmol-Approved_Drug_Library, Targetmol-Natural_Compound_Library, and Targetmol-Bioactive_Compound_Library) and a database of tripeptides. Through this paper, we provided the list of possible chemical ligands (Meglumine, Vidarabine, Adenosine, D-Sorbitol, D-Mannitol, Sodium_gluconate, Ganciclovir and Chlorobutanol) and peptide drugs (combination of isoleucine, lysine and proline) from the databases to guide the experimental scientists and validate the molecules which can combat the virus in a shorter time.

15.
Emerg Microbes Infect ; 9(1): 1259-1268, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-342833

ABSTRACT

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , False Negative Reactions , Humans , Limit of Detection , Pandemics , RNA, Viral/genetics , Viral Load/methods
16.
J Med Virol ; 2020 May 22.
Article in English | MEDLINE | ID: covidwho-342670
17.
Acta Ophthalmol ; 2020 May 21.
Article in English | MEDLINE | ID: covidwho-327245
18.
Nat Med ; 2020 May 19.
Article in English | MEDLINE | ID: covidwho-291852

ABSTRACT

For diagnosis of coronavirus disease 2019 (COVID-19), a SARS-CoV-2 virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test is routinely used. However, this test can take up to 2 d to complete, serial testing may be required to rule out the possibility of false negative results and there is currently a shortage of RT-PCR test kits, underscoring the urgent need for alternative methods for rapid and accurate diagnosis of patients with COVID-19. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value for ruling out SARS-CoV-2 infection, as some patients may have normal radiological findings at early stages of the disease. In this study, we used artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history and laboratory testing to rapidly diagnose patients who are positive for COVID-19. Among a total of 905 patients tested by real-time RT-PCR assay and next-generation sequencing RT-PCR, 419 (46.3%) tested positive for SARS-CoV-2. In a test set of 279 patients, the AI system achieved an area under the curve of 0.92 and had equal sensitivity as compared to a senior thoracic radiologist. The AI system also improved the detection of patients who were positive for COVID-19 via RT-PCR who presented with normal CT scans, correctly identifying 17 of 25 (68%) patients, whereas radiologists classified all of these patients as COVID-19 negative. When CT scans and associated clinical history are available, the proposed AI system can help to rapidly diagnose COVID-19 patients.

20.
Science ; 368(6496): 1274-1278, 2020 06 12.
Article in English | MEDLINE | ID: covidwho-260594

ABSTRACT

Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Coronavirus Infections/therapy , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/therapy , Receptors, Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Disease Models, Animal , Humans , Immunodominant Epitopes/chemistry , Immunodominant Epitopes/immunology , Lung/immunology , Lung/virology , Mice , Neutralization Tests , Pandemics , Protein Domains , Viral Load/immunology
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