Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
2.
Environ Sci Pollut Res Int ; 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1540255

ABSTRACT

COVID-19 has dealt an unprecedented blow to the aviation industry since 2020. This paper applies the interval epsilon-based measure (IEBM) model to evaluate the optimal quarterly environmental efficiency of 14 global airlines of passenger and cargo subsystems during 2018-2020. Then, the time series prediction method is applied to forecast the interval data of inputs and outputs from 2021 to 2022. Finally, we can calculate the quarterly efficiency. Thus, the future development trends of airlines can be predicted. The results show that (1) COVID-19 has hit the passenger subsystem harder, while the freight subsystem has become more efficient; (2) the efficiency of the freight subsystem has inevitably declined in the post-epidemic era; and (3) therefore, the airlines will have a "√" shaped recovery curve in the next few years.

3.
Exp Hematol Oncol ; 10(1): 34, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1526660

ABSTRACT

BACKGROUND: One year into the coronavirus diseases 2019 (COVID-19) pandemic we analyzed the blood coagulopathy in severe and non-severe COVID-19 patients and linked to those of influenza patients for a comparative study. METHODS: We reported 461 COVID-19 patients and 409 seasonal influenza patients admitted at separated medical centers. With their demographic data and medical history, hematological profiles with coagulation characters were emphasized, and compared between two cohorts before and after treatment. RESULTS: For 870 patients included in this study, their median age was (64.0, 51.0-76.0), and among them 511 (58.7%) were male. Hypertension, diabetes, cardiovascular diseases, and bronchitis constituted the leading comorbidities. Upon hospital admission blood test results differentiated COVID-19 patients from influenza cases, and for COVID-19 patients, leukocytosis, neutrophilia, lymphocytopenia, and thrombocytopenia were associated with disease severity and mortality. In addition, COVID-19 cohort demonstrated a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), increased INR, shortened thrombin time and decreased fibrinogen, compared to those in influenza cohort, leaving D-dimer levels indistinguishably high between both cohorts. Platelet hyperreactivity in COVID-19 is more evident, associated with worse hyper-inflammatory response and more refractory coagulopathy. For severe COVID-19 patients administered with anticoagulants, bleeding incidence was substantially higher than others with no anticoagulant medications. CONCLUSIONS: Comparison of coagulation characteristics between COVID-19 and influenza infections provides an insightful view on SARS-CoV-2 pathogenesis and its coagulopathic mechanism, proposing for therapeutic improvement.

4.
Microbiol Spectr ; 9(2): e0135221, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1526454

ABSTRACT

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , Binding Sites/immunology , COVID-19 Vaccines/immunology , Crystallography, X-Ray , Disease Models, Animal , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Mice , Mice, Inbred C57BL , Mice, Transgenic , Protein Interaction Domains and Motifs/immunology , Viral Load/drug effects
6.
Front Med (Lausanne) ; 8: 666629, 2021.
Article in English | MEDLINE | ID: covidwho-1394777

ABSTRACT

Background: Amid the coronavirus disease 2019 (COVID-19) pandemic, we analyzed clinical characteristics of acute lung injury (ALI) in COVID-19 patients and reported their similarity and dissimilarity to those of non-COVID-19 patients in the intensive care unit (ICU). Methods: We reported on 90 COVID-19 and 130 non-COVID-19 ALI patients in the ICUs of multiple centers. Demographic data, medical histories, laboratory findings, and radiological images were analyzed and compared between the two cohorts and within each cohort between survivors and non-survivors. For ALI survivors, clinical characteristics before and after treatment were also compared. Findings: Aberrations in blood parameters, such as leukocytosis, neutrophilia, and thrombocytopenia, were observed in both cohorts. More characteristic abnormalities, including significantly higher red cell distribution width (RDW), C-reactive proteins, and lactic dehydrogenase (LDH) but lower troponin (TnT) and procalcitonin, were observed in the COVID-19 cohort than in the non-COVID-19 cohort, whereas D-dimer levels showed a similar elevation in both cohorts. The COVID-19 cohort also showed more diversified CT patterns where severe features such as consolidations and crazy paving patterns were more frequently observed. Multivariate analysis indicated that age, fever symptom, prothrombin time, procalcitonin, partial pressure of carbon dioxide, oxygenated hemoglobin, and crazy paving patterns in CT scans were independent risk factors associated with COVID-19. Interpretation: Comparison of ALI characteristics between COVID-19 and non-COVID-19 patients in the ICU setting provided insight into the pathogenesis of ALI induced by different risk factors, suggesting distinct treatment plans.

7.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-1387275

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
8.
J Med Virol ; 93(3): 1512-1519, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196466

ABSTRACT

As coronavirus disease 2019 (COVID-19) crashed into the influenza season, clinical characteristics of both infectious diseases were compared to make a difference. We reported 211 COVID-19 patients and 115 influenza patients as two separate cohorts at different locations. Demographic data, medical history, laboratory findings, and radiological characters were summarized and compared between two cohorts, as well as between patients at the intensive care unit (ICU) andnon-ICU within the COVID-19 cohort. For all 326 patients, the median age was 57.0 (interquartile range: 45.0-69.0) and 48.2% was male, while 43.9% had comorbidities that included hypertension, diabetes, bronchitis, and heart diseases. Patients had cough (75.5%), fever (69.3%), expectoration (41.1%), dyspnea (19.3%), chest pain (18.7%), and fatigue (16.0%), etc. Both viral infections caused substantial blood abnormality, whereas the COVID-19 cohort showed a lower frequency of leukocytosis, neutrophilia, or lymphocytopenia, but a higher chance of creatine kinase elevation. A total of 7.7% of all patients possessed no abnormal sign in chest computed tomography (CT) scans. For both infections, pulmonary lesions in radiological findings did not show any difference in their location or distribution. Nevertheless, compared to the influenza cohort, the COVID-19 cohort presented more diversity in CT features, where certain specific CT patterns showed significantly more frequency, including consolidation, crazy paving pattern, rounded opacities, air bronchogram, tree-in-bud sign, interlobular septal thickening, and bronchiolar wall thickening. Differentiable clinical manifestations and CT patterns may help diagnose COVID-19 from influenza and gain a better understanding of both contagious respiratory illnesses.


Subject(s)
COVID-19/diagnosis , Influenza, Human/diagnosis , Lung/diagnostic imaging , Lung/pathology , Adult , Aged , Bronchitis/complications , Comorbidity , Diabetes Complications/complications , Diagnosis, Differential , Female , Heart Diseases/complications , Humans , Hypertension/complications , Length of Stay/statistics & numerical data , Male , Middle Aged , SARS-CoV-2 , Thorax/diagnostic imaging , Tomography, X-Ray Computed
9.
Eur J Radiol ; 134: 109442, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060223

ABSTRACT

PURPOSE: The vascular enlargement (VE) pattern differs from previously described imaging patterns for pneumonia. This study aimed to investigate the incidence, computed tomography (CT) characteristics, and diagnostic value of the VE pattern in coronavirus disease 2019 (COVID-19). METHOD: The CT data of 106 patients with COVID-19 from January 19 to February 29, 2020, and 52 patients with influenza virus pneumonia (IVP) from January 2018 to February 2020 were retrospectively collected. The incidences of the VE pattern between the two groups were compared. The CT manifestations of COVID-19 were analyzed with a particular focus on the VE pattern's specific CT signs, dynamic changes, and relationships with lesion size and disease severity. RESULTS: Peripheral and multilobar ground-glass opacities (GGOs) or mixed GGOs with various sizes and morphologies were typical features of COVID-19 on initial CT. The VE pattern was more common in COVID-19 (88/106, 83.02 %) than in IVP (10/52, 19.23 %) on initial CT (P < 0.001). Three special VE-pattern-specific CT signs, including central vascular sign, ginkgo leaf sign, and comb sign, were identified. Four types of dynamic changes in the VE pattern were observed on initial and follow-up CT, which were closely associated with the evolution of lesions and the time interval from the onset of symptoms to initial CT scan. The VE pattern in COVID-19 was more commonly seen in larger lesions and patients with severe-critical type (all P < 0.001). CONCLUSIONS: The VE pattern is a valuable CT sign for differentiating COVID-19 from IVP, which correlates with more extensive or serious disease. A good understanding of the CT characteristics of the VE pattern may contribute to the early and accurate diagnosis of COVID-19 and prediction of the evolution of lesions.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Pneumonia/diagnostic imaging , Pulmonary Artery/pathology , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/pathology , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Child , Diagnosis, Differential , Female , Humans , Influenza, Human/diagnostic imaging , Influenza, Human/pathology , Lung/blood supply , Lung/pathology , Male , Middle Aged , Pneumonia/pathology , Pulmonary Artery/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Young Adult
11.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-952976

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
14.
Cell ; 182(5): 1271-1283.e16, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-666099

ABSTRACT

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.


Subject(s)
RNA, Messenger/genetics , RNA, Viral/genetics , Vaccines, Synthetic/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Binding Sites , COVID-19 Vaccines , Chlorocebus aethiops , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Female , HEK293 Cells , HeLa Cells , Humans , Immunogenicity, Vaccine , Injections, Intramuscular , Macaca fascicularis , Male , Mice , Mice, Inbred ICR , Nanoparticles/chemistry , RNA, Messenger/metabolism , RNA, Viral/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Th1 Cells/immunology , Vaccine Potency , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vero Cells , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
15.
Cell Host Microbe ; 28(1): 124-133.e4, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-378130

ABSTRACT

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections , Disease Models, Animal , Mice, Inbred C57BL , Pandemics , Pneumonia, Viral , Aging , Angiotensin-Converting Enzyme 2 , Animals , Brain/virology , COVID-19 , CRISPR-Cas Systems , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/blood , Gene Knock-In Techniques , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/pathology , Nose/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2 , Stomach/virology , Trachea/virology , Viral Load , Virus Replication
16.
Mil Med Res ; 7(1): 24, 2020 05 11.
Article in English | MEDLINE | ID: covidwho-232557

ABSTRACT

BACKGROUND: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. METHODS: This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. RESULTS: Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. CONCLUSION: The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.


Subject(s)
Coronavirus Infections/prevention & control , Coronavirus Infections/psychology , Coronavirus Infections/transmission , Health Personnel/psychology , Infection Control/methods , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/psychology , Pneumonia, Viral/transmission , Adult , Betacoronavirus , COVID-19 , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Occupational Exposure , Personal Protective Equipment , SARS-CoV-2 , Stress, Psychological , Surveys and Questionnaires , Tertiary Care Centers , Young Adult
17.
Neurosurgery ; 87(2): E140-E146, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-71966

ABSTRACT

BACKGROUND AND IMPORTANCE: A pituitary adenoma patient who underwent surgery in our department was diagnosed with COVID-19 and 14 medical staff were confirmed infected later. This case has been cited several times but without accuracy or entirety, we feel obligated to report it and share our thoughts on the epidemic among medical staff and performing endonasal endoscopic surgery during COVID-19 pandemic. CLINICAL PRESENTATION: The patient developed a fever 3 d post endonasal endoscopic surgery during which cerebrospinal leak occurred, and was confirmed with SARS-CoV-2 infection later. Several medical staff outside the operating room were diagnosed with COVID-19, while the ones who participated in the surgery were not. CONCLUSION: The deceptive nature of COVID-19 results from its most frequent onset symptom, fever, a cliché in neurosurgery, which makes it hard for surgeons to differentiate. The COVID-19 epidemic among medical staff in our department was deemed as postoperative rather than intraoperative transmission, and attributed to not applying sufficient personal airway protection. Proper personal protective equipment and social distancing between medical staff contributed to limiting epidemic since the initial outbreak. Emergency endonasal endoscopic surgeries are feasible since COVID-19 is still supposed to be containable when the surgeries are performed in negative pressure operating rooms with personal protective equipment and the patients are kept under quarantine postoperatively. However, we do not encourage elective surgeries during this pandemic, which might put patients in conditions vulnerable to COVID-19.


Subject(s)
Adenoma/surgery , Coronavirus Infections/transmission , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Neuroendoscopy/methods , Pituitary Neoplasms/surgery , Pneumonia, Viral/transmission , Adenoma/complications , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Elective Surgical Procedures , Epidemics , Humans , Lung/diagnostic imaging , Male , Nasal Cavity , Natural Orifice Endoscopic Surgery , Neurosurgical Procedures/methods , Operating Rooms , Pandemics , Patient Isolation , Pituitary Neoplasms/complications , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Postoperative Care , SARS-CoV-2 , Tomography, X-Ray Computed
SELECTION OF CITATIONS
SEARCH DETAIL
...