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2.
Proc Natl Acad Sci U S A ; 119(16): e2117142119, 2022 Apr 19.
Article in English | MEDLINE | ID: covidwho-1774040

ABSTRACT

SignificanceCOVID-19 is a deadly rampaging infectious disease with over 480 million cases worldwide. Unfortunately, effective therapies remain very limited. Novel antiviral agents are urgently needed to combat this global healthcare crisis. Here, we elucidate the structural basis for replicase polyprotein cleavage and substrate specificity of SARS-CoV-2 main protease (Mpro). Through analyzing a series of high-resolution structures of SARS-CoV-2 Mpro throughout the proteolytic process, we demonstrate the molecular mechanism of Mpro in proteolytic processing that confers substrate specificity. Substrate selectivity is revealed using structures of the H41A mutant in complex with six individual native cleavage substrates. Our study underscores the mechanistic function of Mpro in the viral life cycle, which provides structural insights to develop effective inhibitors against this essential target of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , Endopeptidases , Humans , Peptide Hydrolases/genetics , Polyproteins/genetics , Protease Inhibitors/chemistry , SARS-CoV-2/genetics , Substrate Specificity
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320685

ABSTRACT

New Ebselen-like derivatives resulted to be very strong in vitro inhibitors of SARS-CoV-2 main protease. We demonstrated that this activity mainly depends on the electrophilicity of the selenium atom that is considerably higher in the N-substituted 1,2- benzoselenazol-3(2H)-ones respect to the corresponding diselenides allowing it to be rapidly attached by free thiols affording sulfur-selenium intermediates that are further subjected to thiol exchange processes. This data paints a very complex scenario that requires us to consider Ebselen and Ebselen-like derivatives as potential electrophilic substrates for the several other free thiols present in the cell beside the target free cysteine. The sulfur selenium intermediates are milder electrophiles that could be theoretically implicated in both the detoxification process as well as in the final enzymatic inhibition. We here demonstrated that the in vitro inhibition activity is not fully reproduced in the prevention of viral replication in the cell-based assay. This indicates that the structure of the substituents introduced in the Ebselen scaffold is a crucial factor to control the reactivity of the selenated molecule in the network of thiol exchanges, as well as for molecular recognition of the targeted enzymatic cysteine. For this reason, an in-depth investigation is strongly desirable to better understand how to increase the activity and the selectivity of Ebselen derivatives overcoming the issues of the apparent PAINS-like role of Ebselen. Furthermore, besides the antiviral activity, thee selected compounds also showed a different ability to reduce the virus-induced cytopathic effect, indicating that other mechanisms could be implicated. One may consider here the well-known cytoprotective antioxidant activity of Ebselen and its derivatives.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313429

ABSTRACT

Accumulating mutations on SARS-CoV-2 Spike (S) protein may increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, in a panel of receptor binding domain (S-RBD) specific monoclonal antibodies (mAbs) with high neutralizing potency against authentic SARS-CoV-2, at least 6 of them were found to efficiently block the pseudovirus of 501Y.V2, a highly transmissible SARS-CoV-2 variant with escape mutations. The top 3 neutralizing Abs (13G9, 58G6 and 510A5) exhibited comparative ultrapotency as those being actively pursued for clinical development. Interestingly, the antigenic sites for the majority of our neutralizing Abs overlapped with a single epitope (13G9e) on S-RBD. Further, the 3-dimensional structures of 2 ultrapotent neutralizing Abs 13G9 or 58G6 in complex with SARS-CoV-2 S trimer demonstrated that both Abs bound to a steric region within S 472–490 . Moreover, a specific linear region (S 450–457 ) was identified as an additional target for 58G6. Importantly, our cryo-electron microscopy (cryo-EM) analysis revealed a unique phenomenon that the S-RBDs interacting with the fragments of antigen binding (Fabs) of 13G9 or 58G6 encoded by the IGHV1-58 and the IGKV3-20 gene segments were universally in the ‘up’ conformation in all observed particles. The potent neutralizing Abs presented in the current study may be promising candidates to fulfill the urgent needs for the current pandemic of SARS-CoV-2, and may of fundamental value for the next-generation vaccine development.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307612

ABSTRACT

Purpose: To describe the correlation between the clinical, laboratory and radiological findings with hospitalization days in Coronavirus Infected Disease-19 (COVID-19) discharged patients. Method In this multicenter study, we retrospectively identified 153 discharged patients with COVID-19 pneumonia from Jan 16, 2020 to Feb 26, 2020 in Hunan province. Patients were grouped based on the hospitalization days: Group 1 (hospitalization days≦12 days) and Group 2((hospitalization days> 12days). Demographic, clinical characteristics and laboratory findings on admission and the imaging features of the first Chest CT on admission were analyzed. The differences between groups were analyzed using univariate logistic regression to find the impact factors. Results The cohort included 153 discharged patients (85 males and 68 females, with the mean age of 42.32±14.03 years old). 90(58.8%) patients had hospitalization days≦12 and 63(41.2%) patients had hospitalization days>12. 44(48.9%) patients in Group1 and 28(44.4%) in Group 2 had been to Wuhan. In both Group1 and Group2, most common symptoms at onset were fever (62.2%, 60.3%) and cough (33.3%, 50.8%). Cough was occurred more common in Group 2(50.8%) than Group 1(33.3%) with a significant difference (p=0.03). 6(6.7%) patients in Group1 and 10(15.9%) in Group2 had admitting diagnosis as non-pneumonia (p=0.07), some of them occurred mild pneumonia during hospital stay. White blood cell (2.2%, 9.5%) and neutrophil (9.5%) count above normal were more common on in Group 2 (p=0.04, p=0.04). Patients in Group 2 had higher concentration of aspartate aminotransferase (P=0.04) than Group 1. Most of patients had multiple lesions (75.6%, 69.8%) with bilateral distribution (73.3%, 58.7%) in both groups. Mixed ground-glass opacity (GGO) and consolidation appearance were seen in most patients. GGO components > consolidation appearance were more common in Group 1(31.1%) than in Group 2(8.0%) with a significant difference between groups (P<0.01). Patients had cough at onset disease (OR, 0.47;95%CI, 0.23 to 0.96, p=0.04) and CT represented as GGO components more than consolidation (OR, 4.84;95%CI, 1.80 to 13.04, p<0.01) were associated with hospitalization days. Conclusions COVID-19 non-pneumonia patients with longer hospitalization days might have the persistent symptoms or pneumonia occurrence after admission. Chest CT could help prompt diagnosis and monitor disease progression, GGO/consolidation >1 in mixed lesions was associated with shorter hospitalization days. Special attention should be paid to the role of radiological features in monitoring disease prognosis.

6.
Front Mol Biosci ; 8: 813248, 2021.
Article in English | MEDLINE | ID: covidwho-1662600

ABSTRACT

The accessory protein Orf6 is uniquely expressed in sarbecoviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is an ongoing pandemic. SARS-CoV-2 Orf6 antagonizes host interferon signaling by inhibition of mRNA nuclear export through its interactions with the ribonucleic acid export 1 (Rae1)-nucleoporin 98 (Nup98) complex. Here, we confirmed the direct tight binding of Orf6 to the Rae1-Nup98 complex, which competitively inhibits RNA binding. We determined the crystal structures of both SARS-CoV-2 and SARS-CoV-1 Orf6 C-termini in complex with the Rae1-Nup98 heterodimer. In each structure, SARS-CoV Orf6 occupies the same potential mRNA-binding groove of the Rae1-Nup98 complex, comparable to the previously reported structures of other viral proteins complexed with Rae1-Nup98, indicating that the Rae1-Nup98 complex is a common target for different viruses to impair the nuclear export pathway. Structural analysis and biochemical studies highlight the critical role of the highly conserved methionine (M58) of SARS-CoVs Orf6. Altogether our data unravel a mechanistic understanding of SARS-CoVs Orf6 targeting the mRNA-binding site of the Rae1-Nup98 complex to compete with the nuclear export of host mRNA, which further emphasizes that Orf6 is a critical virulence factor of SARS-CoVs.

7.
Nat Commun ; 12(1): 6304, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500462

ABSTRACT

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/chemistry , Antibodies, Viral/administration & dosage , Antibodies, Viral/chemistry , Binding Sites , COVID-19/pathology , COVID-19/virology , Epitopes , Humans , Mice , Mice, Transgenic , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Load/drug effects , Weight Loss/drug effects
9.
Nat Rev Microbiol ; 19(11): 685-700, 2021 11.
Article in English | MEDLINE | ID: covidwho-1428872

ABSTRACT

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an unprecedented global health crisis. However, therapeutic options for treatment are still very limited. The development of drugs that target vital proteins in the viral life cycle is a feasible approach for treating COVID-19. Belonging to the subfamily Orthocoronavirinae with the largest RNA genome, SARS-CoV-2 encodes a total of 29 proteins. These non-structural, structural and accessory proteins participate in entry into host cells, genome replication and transcription, and viral assembly and release. SARS-CoV-2 proteins can individually perform essential physiological roles, be components of the viral replication machinery or interact with numerous host cellular factors. In this Review, we delineate the structural features of SARS-CoV-2 from the whole viral particle to the individual viral proteins and discuss their functions as well as their potential as targets for therapeutic interventions.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2/chemistry , Viral Proteins/chemistry , COVID-19/virology , Drug Delivery Systems , Genome, Viral , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viral Proteins/genetics
10.
Cell ; 184(6): 1604-1620, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1392179

ABSTRACT

Historically, emerging viruses appear constantly and have cost millions of human lives. Currently, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, effective antivirals, especially those targeting the conserved protein in multiple unrelated viruses, such as the compounds targeting RNA-dependent RNA polymerase, are urgently needed to combat more emerging and re-emerging viruses in the future. Here we reviewed the development of antivirals with common targets, including those against the same protein across viruses, or the same viral function, to provide clues for development of antivirals for future epidemics.


Subject(s)
Antiviral Agents/therapeutic use , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Molecular Targeted Therapy/methods , Pandemics , Virus Diseases/drug therapy , Virus Diseases/epidemiology , Viruses/enzymology , Animals , Antiviral Agents/pharmacology , Communicable Diseases, Emerging/virology , Humans , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Viral Envelope Proteins/antagonists & inhibitors , Virus Diseases/virology , Virus Internalization/drug effects
11.
Chem Commun (Camb) ; 57(12): 1430-1433, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1387498

ABSTRACT

The main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some ß-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.


Subject(s)
Antiviral Agents/pharmacology , Cysteine Endopeptidases/drug effects , Mass Spectrometry/methods , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , beta-Lactams/pharmacology , Acylation , Antiviral Agents/chemistry , COVID-19/virology , Catalytic Domain , High-Throughput Screening Assays , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , beta-Lactams/chemistry
12.
Nat Commun ; 12(1): 3061, 2021 05 24.
Article in English | MEDLINE | ID: covidwho-1387342

ABSTRACT

The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro), critical for viral replication, is a key target for therapeutic development. An organoselenium drug called ebselen has been demonstrated to have potent Mpro inhibition and antiviral activity. We have examined the binding modes of ebselen and its derivative in Mpro via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger Mpro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. A free selenium atom bound with cysteine of catalytic dyad has been revealed in crystallographic structures of Mpro with ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct and formation of a phenolic by-product, confirmed by mass spectrometry. The target engagement with selenation mechanism of inhibition suggests wider therapeutic applications of these compounds against SARS-CoV-2 and other zoonotic beta-corona viruses.


Subject(s)
Azoles/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Organoselenium Compounds/pharmacology , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Azoles/chemistry , Catalytic Domain , Coronavirus 3C Proteases/metabolism , Crystallography, X-Ray , Cysteine/chemistry , Hydrolysis , Isoindoles , Models, Molecular , Organoselenium Compounds/chemistry , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Reference Standards , SARS-CoV-2/drug effects , Salicylanilides/chemistry , Salicylanilides/pharmacology , Selenium/metabolism
14.
Protein Cell ; 12(11): 877-888, 2021 11.
Article in English | MEDLINE | ID: covidwho-1188202

ABSTRACT

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 µmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.


Subject(s)
Coronavirus Papain-Like Proteases/chemistry , High-Throughput Screening Assays/methods , Protease Inhibitors/chemistry , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Coronavirus Papain-Like Proteases/genetics , Coronavirus Papain-Like Proteases/metabolism , Crystallography, X-Ray , Drug Evaluation, Preclinical , Drug Repositioning , Humans , Imidazoles/chemistry , Imidazoles/metabolism , Imidazoles/therapeutic use , Inhibitory Concentration 50 , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Naphthoquinones/chemistry , Naphthoquinones/metabolism , Naphthoquinones/therapeutic use , Protease Inhibitors/metabolism , Protease Inhibitors/therapeutic use , Protein Structure, Tertiary , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , SARS-CoV-2/isolation & purification
15.
Biochem Biophys Res Commun ; 538: 63-71, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-1125596

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented global health crisis. It is particularly urgent to develop clinically effective therapies to contain the pandemic. The main protease (Mpro) and the RNA-dependent RNA polymerase (RdRP), which are responsible for the viral polyprotein proteolytic process and viral genome replication and transcription, respectively, are two attractive drug targets for SARS-CoV-2. This review summarizes up-to-date progress in the structural and pharmacological aspects of those two key targets above. Different classes of inhibitors individually targeting Mpro and RdRP are discussed, which could promote drug development to treat SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus Protease Inhibitors/chemistry , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Enzyme Inhibitors/chemistry , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Coronavirus Protease Inhibitors/pharmacology , Drug Design , Enzyme Inhibitors/pharmacology , Humans , Protein Conformation , SARS-CoV-2/drug effects
16.
Sci Rep ; 11(1): 4304, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1096330

ABSTRACT

To determine the correlation between the clinical, laboratory, and radiological findings and the hospitalization days in Coronavirus Infectious Disease-19 (COVID-19) discharged patients. We retrospectively identified 172 discharged patients with COVID-19 pneumonia from January 10, 2020, to February 28, 2020, in Hunan province. The patients were categorized into group 1 (≤ 19 days) and group 2 (> 19 days) based on the time from symptom onset to discharge. Cough during admission occurred more commonly in group 2 (68.4%) than in group 1 (53.1%, p = 0.042). White blood cell (p = 0.045), neutrophil counts (p = 0.023), Alanine aminotransferase (p = 0.029), Aspartate aminotransferase (p = 0.027) and Lactate dehydrogenase (p = 0.021) that were above normal were more common in group 2. Patients with single lesions were observed more in group 1(17.7%, p = 0.018) and multiple lesions observed more in group 2(86.8%, p = 0.012). The number of lobes involved (p = 0.008) in the CT score (p = 0.001) for each patient was all differences between the two groups with a statistically significant difference. Mixed ground-glass opacity (GGO) and consolidation appearances were observed in most patients. GGO components > consolidation appearance was more common in group 1 (25.0%) than in group 2 (8.0%) with a significant difference (0.015), GGO < consolidation was more common in group 2(71.1%, p = 0.012). From the logistic regression analysis, the CT score (OR, 1.223; 95% CI, 1.004 to 1.491, p = 0.046) and the appearance of GGO > consolidation (OR, 0.150; 95% CI, 0.034 to 0.660, p = 0.012) were independently associated with the hospitalization days. Thus, special attention should be paid to the role of radiological features in monitoring the disease prognosis.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/pathology , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , COVID-19/blood , China , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Patient Discharge/statistics & numerical data , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
17.
Chem Commun (Camb) ; 57(12): 1430-1433, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1035940

ABSTRACT

The main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some ß-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.


Subject(s)
Antiviral Agents/pharmacology , Cysteine Endopeptidases/drug effects , Mass Spectrometry/methods , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , beta-Lactams/pharmacology , Acylation , Antiviral Agents/chemistry , COVID-19/virology , Catalytic Domain , High-Throughput Screening Assays , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , beta-Lactams/chemistry
18.
Front Mol Biosci ; 7: 616341, 2020.
Article in English | MEDLINE | ID: covidwho-993386

ABSTRACT

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) rapidly turned into an unprecedented pandemic of coronavirus disease 2019 (COVID-19). This global healthcare emergency marked the third occurrence of a deadly coronavirus (CoV) into the human society after entering the new millennium, which overwhelmed the worldwide healthcare system and affected the global economy. However, therapeutic options for COVID-19 are still very limited. Developing drugs targeting vital proteins in viral life cycle is a feasible approach to overcome this dilemma. Main protease (Mpro) plays a dominant role in processing CoV-encoded polyproteins which mediate the assembly of replication-transcription machinery and is thus recognized as an ideal antiviral target. Here we summarize the recent progress in the discovery of anti-SARS-CoV-2 agents against Mpro. Combining structural study, virtual screen, and experimental screen, numerous therapeutic candidates including repurposed drugs and ab initio designed compounds have been proposed. Such collaborative effort from the scientific community would accelerate the pace of developing efficacious treatment for COVID-19.

19.
Virol J ; 17(1): 159, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-883582

ABSTRACT

OBJECTIVE: Aimed to summarize the characteristics of chest CT imaging in Chinese hospitalized patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine. METHODS: PubMed, Embase and Web of Science databases were searched to identify relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R i386 4.0.0 software. Random-effects models were employed to calculate pooled mean differences. RESULTS: 19 retrospective studies (1332 cases) were included. The results demonstrated that the combined proportion of ground-glass opacities (GGO) was 0.79 (95% CI 0.68, 0.89), consolidation was 0.34 (95% CI 0.23, 0.47); mixed GGO and consolidation was 0.46 (95% CI 0.37; 0.56); air bronchogram sign was 0.41 (95% CI 0.26; 0.55); crazy paving pattern was 0.32 (95% CI 0.17, 0.47); interlobular septal thickening was 0.55 (95% CI 0.42, 0.67); reticulation was 0.30 (95% CI 0.12, 0.48); bronchial wall thickening was 0.24 (95% CI 0.11, 0.40); vascular enlargement was 0.74 (95% CI 0.64, 0.86); subpleural linear opacity was 0.28 (95% CI 0.12, 0.48); intrathoracic lymph node enlargement was 0.03 (95% CI 0.00, 0.07); pleural effusions was 0.03 (95% CI 0.02, 0.06). The distribution in lung: the combined proportion of central was 0.05 (95% CI 0.01, 0.11); peripheral was 0.74 (95% CI 0.62, 0.84); peripheral involving central was 0.38 (95% CI 0.19, 0.75); diffuse was 0.19 (95% CI 0.06, 0.32); unifocal involvement was 0.09 (95% CI 0.05, 0.14); multifocal involvement was 0.57 (95% CI 0.48, 0.68); unilateral was 0.16 (95% CI 0.10, 0.23); bilateral was 0.83 (95% CI 0.78, 0.89); The combined proportion of lobes involved (> 2) was 0.70 (95% CI 0.61, 0.78); lobes involved (≦ 2) was 0.35 (95% CI 0.26, 0.44). CONCLUSION: GGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19, which distribution features were peripheral, bilateral, involved lobes > 2. Therefore, based on chest CT features of COVID-19 mentioned, it might be a promising means for identifying COVID-19.


Subject(s)
Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Databases, Factual , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Young Adult
20.
J Int Med Res ; 48(9): 300060520956834, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-791644

ABSTRACT

PURPOSE: To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. METHODS: Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. RESULTS: Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. CONCLUSION: The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Infectious Disease Incubation Period , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Adolescent , Adult , Aged , Biomarkers/analysis , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , Hospitalization/statistics & numerical data , Humans , Logistic Models , Male , Middle Aged , Pandemics , Patient Discharge/statistics & numerical data , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
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