Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Eur J Med Chem ; 241: 114659, 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2035972

ABSTRACT

Cytokine storm is a key feature of sepsis and severe stage of COVID-19, and the immunosuppression after excessive immune activation is a substantial hazard to human life. Both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by various pattern recognition receptors (PRRs), which lead to the immune response. A number of neolignan analogues were synthesized in this work and showed powerful anti-inflammation properties linked to the response to innate and adaptive immunity, as well as NP-7 showed considerable anti-inflammatory activity at 100 nM. On the sepsis model caused by cecum ligation and puncture (CLP) in C57BL/6J mice, NP-7 displayed a strong regulatory influence on cytokine release. Then a photo-affinity probe of NP-7 was synthesized and chemoproteomics based on stable isotope labeling with amino acids in cell cultures (SILAC) identified Immunity-related GTPase M (IRGM) as a target suppressing cytokine storm, which was verified by competitive pull-down, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and molecular dynamics simulations.


Subject(s)
Anti-Inflammatory Agents , Cytokine Release Syndrome , GTP-Binding Proteins , Sepsis , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , COVID-19 , Cytokine Release Syndrome/drug therapy , Cytokines/metabolism , Disease Models, Animal , GTP-Binding Proteins/metabolism , Humans , Mice , Mice, Inbred C57BL , Proteomics
2.
Crit Care ; 26(1): 171, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1951302

ABSTRACT

BACKGROUND: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin-angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated. METHODS AND RESULTS: Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT1R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII. CONCLUSION: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT1R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.


Subject(s)
Acute Lung Injury , Angiotensin-Converting Enzyme 2 , COVID-19 , Respiratory Distress Syndrome , Acute Lung Injury/prevention & control , Acute Lung Injury/virology , Angiotensin II , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , COVID-19/complications , Humans , Lipopolysaccharides , Mice , Recombinant Proteins/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Aging Clin Exp Res ; 34(10): 2557-2565, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1920348

ABSTRACT

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.


Subject(s)
COVID-19 , Frailty , Humans , Aged , Frailty/epidemiology , Frail Elderly , Pandemics , Ontario/epidemiology
4.
J Am Coll Clin Pharm ; 3(5): 866-868, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1898806
5.
Respir Res ; 23(1): 133, 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1869087

ABSTRACT

BACKGROUND: Considering the considerable prevalence of allergic disease in the general population, an urgent need exists for inactivated SARS-CoV-2 vaccines that can be safely administered to those subjects. METHODS: This retrospective cohort study including 1926 participants who received inactivated SARS-CoV-2 vaccines, compared their local and systemic reactions in 7 days after each dose of inactivated SARS-CoV-2 vaccine, and anti-SARS-CoV-2 IgG after vaccination in all participants. RESULTS: Pain at the injection site within seven days after the first injection was the most commonly reported local reaction, occurring in 31.0% of the patients with allergic disease and 18.9% in the control group, respectively (P < 0.001). After the first dose, systemic events were more frequently reported in patients with allergic disease than control group (30.2% vs. 22.9%, P < 0.001). After the second dose, systemic events occurred less often, affecting 17.1% of the patients with allergic disease and 11.1% of the control group (P < 0.002). The occurrence of fatigue, vertigo, diarrhea, skin rash, sore throat were the most frequent systemic reactions. Overall, a lower incidence of local and systemic reactive events was observed after the second dose than the first dose in patients with allergic disease and control group. Nearly all participants had positive IgG antibodies, and participants with allergic disease had higher frequencies compared with control group (100.0 vs.99.4%). CONCLUSIONS: Although local and systemic reactions were more frequently reported in patients with allergic disease than control group, administration of the inactivated SARS-CoV-2 vaccine was safe and well tolerated by all participants; no participants experienced a serious adverse event, and none were hospitalized. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100048549. Registered Jul 10, 2021.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunoglobulin G , Retrospective Studies , SARS-CoV-2
6.
Can J Cardiol ; 37(10): 1547-1554, 2021 10.
Article in English | MEDLINE | ID: covidwho-1439940

ABSTRACT

BACKGROUND: The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. METHODS: Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. RESULTS: We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. CONCLUSIONS: There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.


Subject(s)
COVID-19 , Cardiovascular Diseases , Coronary Artery Bypass/statistics & numerical data , Delayed Diagnosis , Percutaneous Coronary Intervention/statistics & numerical data , Transcatheter Aortic Valve Replacement/statistics & numerical data , Waiting Lists/mortality , COVID-19/epidemiology , COVID-19/prevention & control , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/psychology , Cardiovascular Diseases/surgery , Delayed Diagnosis/psychology , Delayed Diagnosis/statistics & numerical data , Delivery of Health Care/statistics & numerical data , Female , Humans , Infection Control/methods , Male , Middle Aged , Mortality , Ontario/epidemiology , SARS-CoV-2 , Time-to-Treatment/organization & administration
7.
CJC Open ; 3(10): 1214-1216, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1240244

ABSTRACT

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in patients with ST-segment elevation myocardial infarction (STEMI) has not been fully described. METHODS: All patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in Ontario, Canada between March 1 and September 30, 2020 were included. Rates of positive COVID-19 tests from January 1, 2020 to the date of STEMI presentation were ascertained. For comparison, COVID-19 results were also evaluated in the adult Ontario population between January 1, 2020 and September 30, 2020, using provincial laboratory testing data. RESULTS: There were 3606 unique patients presenting with STEMI and receiving PCI in Ontario, Canada during the study period. Sixteen patients (0.44%) tested positive for COVID-19. The background infection rate among all 12,448,541 Ontario residents was similar, at 0.34%. CONCLUSIONS: The results of this population-based analysis suggest that proceeding with primary PCI with appropriate infection control practices is reasonable when community infection rates are low.


CONTEXTE: L'incidence de la maladie à coronavirus 2019 (COVID-19) chez les patients présentant un infarctus du myocarde avec élévation du segment ST (STEMI) n'a pas été entièrement décrite. MÉTHODOLOGIE: Tous les patients atteints de STEMI ayant subi une intervention coronarienne percutanée (ICP) primaire en Ontario (Canada) entre le 1er mars et le 30 septembre 2020 ont été inclus. Les taux de tests positifs à la COVID entre le 1er janvier 2020 et le moment de la présentation du STEMI ont été vérifiés. Aux fins de comparaison, les résultats des tests de dépistage de la COVID-19 ont également été évalués au sein de la population adulte de l'Ontario entre le 1er janvier 2020 et le 30 septembre 2020 au moyen des données des laboratoires provinciaux. RÉSULTATS: Pendant la période d'étude, 3 606 patients présentant un STEMI et ayant subi une ICP en Ontario (Canada) ont été recensés. Seize patients (0,44 %) ont reçu un résultat positif au test de dépistage de la COVID-19. Le taux d'infection parmi les 12 448 541 résidents de l'Ontario était similaire, soit 0,34 %. CONCLUSIONS: Les résultats de cette analyse populationnelle portent à penser qu'il est raisonnable de procéder à une ICP primaire avec des mesures appropriées de contrôle des infections lorsque les taux d'infection dans la collectivité sont faibles.

8.
Brain Behav ; 11(6): e02185, 2021 06.
Article in English | MEDLINE | ID: covidwho-1230195

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 is spreading throughout the whole world as a public health issue. There is a link between the new coronavirus and changes in biochemical indicators, such as coagulation functions. Hypercoagulable state of blood caused by infections may lead to cerebrovascular diseases. More attention should be paid to patients with COVID-19, especially critically ill individuals with history of cerebrovascular disease who may have high risk of stroke. METHODS: 193 patients with COVID-19 were enrolled in the study. These patients were categorized into nonsevere (143 patients) and severe (50 patients) groups. This study evaluated laboratory tests, including routine blood tests, C-reactive protein, erythrocyte sedimentation rate, electrolytes, and coagulation functions. Furthermore, neurological function and stroke risks were evaluated in this study. RESULTS: Compared to the nonsevere group, there were increases in white blood cells, neutrophil count, interleukin-6, erythrocyte sedimentation rate, and C-reactive protein in the severe group (p < .05). For coagulation functions, parameters like prothrombin time, international normalized ratio, activated partial thromboplastin time, thrombin time, D-dimer, and fibrin degradation products were increased significantly in the severe group (p < .01). Severe patients also demonstrated higher scores on the Framingham stroke risk profile and lower Glasgow scores (p < .05). Furthermore, significant associations were noticed between stroke risk and age, blood cell count, neutrophil count, D-dimmer, and fibrin degradation productions (p < .05). CONCLUSIONS: Data suggested that coagulation functions were affected in patients with COVID-19. Hypercoagulable state in patients may lead to potential high risk of stroke.


Subject(s)
COVID-19 , Stroke , Humans , Leukocyte Count , Partial Thromboplastin Time , SARS-CoV-2 , Stroke/epidemiology
9.
Signal Transduct Target Ther ; 6(1): 107, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1117676

ABSTRACT

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.


Subject(s)
COVID-19 Drug Treatment , Dexamethasone/administration & dosage , Interferons/administration & dosage , SARS-CoV-2 , Adult , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Dexamethasone/agonists , Drug Synergism , Female , Humans , Interferons/agonists , Male , Middle Aged , Retrospective Studies
10.
J Med Internet Res ; 23(1): e24619, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1041500

ABSTRACT

BACKGROUND: The COVID-19 outbreak has increased challenges associated with health management, especially cancer management. In an effort to provide continuous pharmaceutical care to cancer patients, Sun Yat-sen University Cancer Center (SYSUCC) implemented a remote pharmacy service platform based on its already existing web-based hospital app known as Cloud SYSUCC. OBJECTIVE: The aim of this study was to investigate the characteristics, acceptance, and initial impact of the Cloud SYSUCC app during a COVID-19 outbreak in a tertiary cancer hospital in China. METHODS: The total number of online prescriptions and detailed information on the service were obtained during the first 6 months after the remote service platform was successfully set up. The patients' gender, age, residence, primary diagnosis, drug classification, weekly number of prescriptions, and prescribed drugs were analyzed. In addition, a follow-up telephonic survey was conducted to evaluate patients' satisfaction in using the remote prescription service. RESULTS: A total of 1718 prescriptions, including 2022 drugs for 1212 patients, were delivered to 24 provinces and municipalities directly under the Central Government of China between February 12, 2020, and August 11, 2020. The majority of patients were female (841/1212, 69.39%), and 90.18% (1093/1212) of them were aged 31-70 years old. The top 3 primary diagnoses for which remote medical prescriptions were made included breast cancer (599/1212, 49.42%), liver cancer (249/1212, 20.54%), and thyroid cancer (125/1212, 10.31%). Of the 1718 prescriptions delivered, 1435 (83.5%) were sent to Guangdong Province and 283 (16.5%) were sent to other provinces in China. Of the 2022 drugs delivered, 1012 (50.05%) were hormonal drugs. The general trend in the use of the remote prescription service declined since the 10th week. A follow-up telephonic survey found that 88% (88/100) of the patients were very satisfied, and 12% (12/100) of the patients were somewhat satisfied with the remote pharmacy service platform. CONCLUSIONS: The remote pharmacy platform Cloud SYSUCC is efficient and convenient for providing continuous pharmaceutical care to patients with cancer during the COVID-19 crisis. The widespread use of this platform can help to reduce person-to-person transmission as well as infection risk for these patients. Further efforts are needed to improve the quality and acceptance of the Cloud SYSUCC platform, as well as to regulate and standardize the management of this novel service.


Subject(s)
COVID-19/epidemiology , Neoplasms/drug therapy , Patient Satisfaction , Pharmacy Service, Hospital/statistics & numerical data , SARS-CoV-2 , Telemedicine/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Female , Humans , Middle Aged , Pandemics , Surveys and Questionnaires , Tertiary Care Centers , Young Adult
11.
Vaccine ; 39(8): 1241-1247, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1039581

ABSTRACT

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , Epitopes, T-Lymphocyte/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibody Formation , COVID-19 , Female , Humans , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
12.
J Tradit Complement Med ; 11(2): 180-187, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1032412

ABSTRACT

BACKGROUND AND AIM: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. EXPERIMENTAL PROCEDURE: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected. RESULTS AND CONCLUSION: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. TAXONOMY CLASSIFICATION BY EVISE: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

13.
Cell Host Microbe ; 28(3): 455-464.e2, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-654072

ABSTRACT

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19 , Child , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Drug Therapy, Combination , Female , Hospital Mortality , Host Microbial Interactions/drug effects , Humans , Indoles/administration & dosage , Interferon alpha-2 , Interferon-alpha/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Retrospective Studies , Ritonavir/administration & dosage , SARS-CoV-2 , Treatment Outcome , Young Adult , COVID-19 Drug Treatment
14.
Vaccine ; 38(32): 5071-5075, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-592568

ABSTRACT

SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.


Subject(s)
Betacoronavirus/chemistry , Drug Design , Models, Immunological , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/chemistry , Viral Vaccines/immunology , Amino Acid Sequence , Antigens, Viral/chemistry , Antigens, Viral/immunology , Betacoronavirus/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Humans , Models, Molecular , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2 , Sequence Alignment , Vaccines, Subunit/chemistry , Vaccines, Subunit/immunology
15.
Anal Chem ; 92(13): 9399-9404, 2020 07 07.
Article in English | MEDLINE | ID: covidwho-342738

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a public health emergency. The reverse transcriptase real-time quantitative PCR (qRT-PCR) test is currently considered as the gold standard in the laboratory for the etiological detection of COVID-19. However, qRT-PCR results could be false-negative due to the inadequate sensitivity of qRT-PCR. In this study, we have developed and evaluated a novel one-step single-tube nested quantitative real-time PCR (OSN-qRT-PCR) assay for the highly sensitive detection of SARS-CoV-2 targeting the ORF1ab and N genes. The sensitivity of the OSN-qRT-PCR assay was 1 copy/reaction and 10-fold higher than that of the commercial qRT-PCR kit (10 copies/reaction). The clinical performance of the OSN-qRT-PCR assay was evaluated using 181 clinical samples. Among them, 14 qRT-PCR-negative samples (7 had no repetitive results and 7 had no cycle threshold (CT) values) were detected by OSN-qRT-PCR. Moreover, the 7 qRT-PCR-positives in the qRT-PCR gray zone (CT values of ORF1ab ranged from 37.48 to 39.07, and CT values of N ranged from 37.34 to 38.75) were out of the gray zone and thus were deemed to be positive by OSN-qRT-PCR, indicating that the positivity of these samples is confirmative. Compared to the qRT-PCR kit, the OSN-qRT-PCR assay revealed higher sensitivity and specificity, showing better suitability to clinical applications for the detection of SARS-CoV-2 in patients with low viral load.


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , Adult , Aged , Aged, 80 and over , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins , Female , Humans , Male , Middle Aged , Nucleocapsid Proteins/genetics , Pandemics , Phosphoproteins , Pneumonia, Viral/virology , Polyproteins , RNA, Viral/genetics , RNA, Viral/metabolism , SARS-CoV-2 , Sensitivity and Specificity , Viral Proteins/genetics
16.
Clinical Microbiology and Infection ; 2020.
Article | WHO COVID | ID: covidwho-276597

ABSTRACT

Objectives To evaluate the performance of an ultra-fast single-tube nucleic acid isothermal amplification detection assay for SARS-CoV-2 RNA using clinical samples from multiple centers. Methods A reverse transcription recombinase-aided amplification (RT-RAA) assay for SARS-CoV-2 was conducted within 15minutesat39°C with portable instruments after addition of extracted RNA. The clinical performance of RT-RAA assay was evaluated using 947 clinical samples from five institutions in four regions of China, and the approved commercial real-time fluorescent RT-PCR (qRT-PCR) kits were used for parallel detection. The sensitivity and specificity of RT-RAA were compared and analyzed. Results The RT-RAA test results of 926 samples were consistent with those of qRT-PCR (330 were positive, 596 were negative) and 21 were inconsistent. The sensitivity and specificity of RT-RAA was 97.63% [330/338, 95% confidence interval (CI): 95.21 to 98.90] and 97.87% (596/609, 95% CI: 96.28 to 98.81), respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 96.21% (330/343, 95% CI: 93.45 to 97.88), and 98.68% (596/604, 95% CI: 97.30 to 99.38), respectively. The total coincidence rate was 97.78% (926/947, 95% CI: 96.80 to 98.70) and the Kappa was 0.952 (P <0.05). Conclusion With comparable sensitivity and specificity to the commercial qRT-PCR kits, RT-RAA assay for SARS-CoV-2 exhibited distinctive advantages of simplicity and rapidity in terms of operation and turn-around time.

17.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 164-167, 2020 Feb 29.
Article in Chinese | MEDLINE | ID: covidwho-213369

ABSTRACT

The ongoing epidemic of caused by the coronavirus SARS-CoV-2 starting in December 2019 poses a serious public health threat globally. The virus is highly infectious and transmitted mainly through droplets and contacts, and is associated with a high risk of pneumonia. A small number of patients may present with acute respiratory distress syndrome with severe respiratory complications, which can lead even to death. The selection of appropriate detection techniques and methods for accurate and rapid identification of pathogens therefore plays a key role in improving the diagnosis and treatment of the patients and containing the outbreak. In this review, the authors gives an overview of the virus laboratory detection technology, including virus isolation and culture, real-time fluorescent PCR, gene sequencing, serological antibody detection, and the gene editing technology based on CRISPR/Cas13 system. These techniques are expected to provide valuable assistance in controlling the epidemic and new ideas for future researches.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Antibodies, Viral/analysis , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Clustered Regularly Interspaced Short Palindromic Repeats , Humans , Pandemics , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Sequence Analysis , Serologic Tests
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(2): 246-250, 2020 Apr 25.
Article in Chinese | MEDLINE | ID: covidwho-116797

ABSTRACT

Recently a COVID-19 pneumonia pandemic caused by a novel coronavirus 2019-nCoV has broken out over the world. In order to better control the spread of the pandemic, there's an urgent need to extensively study the virus' origin and the mechanisms for its infectivity and pathogenicity. Spike protein is a special structural protein on the surface of coronavirus. It contains important information about the evolution of the virus and plays critical roles in the processes of cellular recognition and entry. In the past decades, spike protein has always been one of the most important objects in research works on coronaviruses closely related to human life. In this review we introduce these research works related to spike proteins, hoping it will provide reasonable ideas for the control of the current pandemic, as well as for the diagnosis and treatment of COVID-19.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Spike Glycoprotein, Coronavirus/analysis , Betacoronavirus , COVID-19 , Evolution, Molecular , Humans , Pandemics , SARS-CoV-2
19.
Int J Clin Pharm ; 42(2): 305-308, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-30954

ABSTRACT

In the Chinese coronavirus epicenter, Wuhan, 16 cabin hospitals were built to admit patients with confirmed coronavirus infection (COVID-19). These cabin hospitals serve the role of effectively quarantine and treat mild cases of patients infected with COVID-19. Each cabin hospital has pharmacists to provide services and pharmaceutical care to patients. Pharmacists also provide assistance to cabin hospitals through remote internet platforms across China. In this commentary, we describe pharmacy services at cabin hospitals to share our experiences with the international pharmacy community.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , COVID-19 , Coronavirus Infections/epidemiology , Epidemics , Hospitals , Humans , Pandemics , Pharmacy Service, Hospital , Pneumonia, Viral/epidemiology , SARS-CoV-2 , COVID-19 Drug Treatment
SELECTION OF CITATIONS
SEARCH DETAIL