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1.
Radiology ; 302(3): 709-719, 2022 03.
Article in English | MEDLINE | ID: covidwho-1702660

ABSTRACT

Background The chest CT manifestations of COVID-19 from hospitalization to convalescence after 1 year are unknown. Purpose To assess chest CT manifestations of COVID-19 up to 1 year after symptom onset. Materials and Methods Patients were enrolled if they were admitted to the hospital because of COVID-19 and underwent CT during hospitalization at two isolation centers between January 27, 2020, and March 31, 2020. In a prospective study, three serial chest CT scans were obtained at approximately 3, 7, and 12 months after symptom onset and were longitudinally analyzed. The total CT score of pulmonary lobe involvement, ranging from 0 to 25, was assessed (score of 1-5 for each lobe). Univariable and multivariable logistic regression analyses were performed to explore independent risk factors for residual CT abnormalities after 1 year. Results A total of 209 study participants (mean age, 49 years ± 13 [standard deviation]; 116 women) were evaluated. CT abnormalities had resolved in 61% of participants (128 of 209) at 3 months and in 75% of participants (156 of 209) at 12 months. Among participants with chest CT abnormalities that had not resolved, there were residual linear opacities in 25 of the 209 participants (12%) and multifocal reticular or cystic lesions in 28 of the 209 participants (13%). Age 50 years or older, lymphopenia, and severe or aggravation of acute respiratory distress syndrome were independent risk factors for residual CT abnormalities at 1 year (odds ratios = 15.9, 18.9, and 43.9, respectively; P < .001 for each comparison). In 53 participants with residual CT abnormalities at 12 months, reticular lesions (41 of 53 participants [77%]) and bronchial dilation (39 of 53 participants [74%]) were observed at discharge and were persistent in 28 (53%) and 24 (45%) of the 53 participants, respectively. Conclusion One year after COVID-19 diagnosis, chest CT scans showed abnormal findings in 53 of the 209 study participants (25%), with 28 of the 209 participants (13%) showing subpleural reticular or cystic lesions. Older participants with severe COVID-19 or acute respiratory distress syndrome were more likely to develop lung sequelae that persisted at 1 year. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Wi et al in this issue.


Subject(s)
COVID-19/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed/methods , Disease Progression , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pneumonia, Viral/virology , Prospective Studies , Risk Factors , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318609

ABSTRACT

Objectives: To compare the chest computed tomography (CT) findings between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19). Materials: and Methods Between 12 January 2020 to 20 February 2020, the records of 124 consecutive patients diagnosed with COVID-19 were retrospectively reviewed and divided into survivor (83/124) and non-survivor (41/124) groups. Chest CT findings were qualitatively compared on admission and serial chest CT scans were semi-quantitively evaluated between two groups using curve estimations. Results: Elder age (median: 69 vs. 43y, p<0.001), higher male ratio (31/41 vs. 32/83, p<0.001), and more comorbidities were observed in non-survivor group. On admission, significantly more bilateral (97.6% vs. 73.5%, p=0.005) and diffuse lesions (39.0% vs. 8.4%, p<0.001) with higher total CT score (median: 10 vs. 4) were observed in non-survivor group compared with survivor group. Besides, crazy-paving pattern was more predominant in non- survivor group than survivor group (39.0% vs. 12.0%, p=0.004). From the prediction of curve estimation, in survivor group total CT score increased in the first 20 days reaching the peak of 6 points and then gradual decreased for more than other 40 days (R2=0.545, p<0.001). In non- survivor group, total CT score rapidly increased over 10 points in the first 10 days and gradually increased afterwards until ARDS occurred with following death events (R2=0.711, p<0.001). Conclusions: Persistent progression with predominant crazy-paving pattern was the major manifestation of COVID-19 in non-survivors. Understanding this CT feature could help the clinical physician to predict the prognosis of the patients.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318608

ABSTRACT

Objectives: This study aims to explore and compare a novel deep learning-based quantification with the conventional semi-quantitative computed tomography (CT) scoring for the serial chest CT scans of COVID-19. Materials: and Methods: 95 patients with confirmed COVID-19 and a total of 465 serial chest CT scans were involved, including 61 moderate patients (moderate group, 319 chest CT scans) and 34 severe patients (severe group, 146 chest CT scans). Conventional CT scoring and deep learning-based quantification were performed for all chest CT scans for two study goals: 1. Correlation between these two estimations;2. Exploring the dynamic patterns using these two estimations between moderate and severe groups. Results: : The Spearman’s correlation coefficient between these two estimation methods was 0.920 ( p <0.001). predicted pulmonary involvement (CT score and percent of pulmonary lesions calculated using deep learning-based quantification) increased more rapidly and reached a higher peak on 23 rd days from symptom onset in severe group, which reached a peak on 18 th days in moderate group with faster absorption of the lesions. Conclusions: : The deep learning-based quantification for COVID-19 showed a good correlation with the conventional CT scoring and demonstrated a potential benefit in the estimation of disease severities of COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315581

ABSTRACT

Background: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia were discharged from hospitals in Wuhan, China. We aimed to determine the cumulative percentage of complete radiological resolution at each time point, to explore the relevant affecting factors, and to describe the chest CT findings at different time points after hospital discharge. Methods: : Patients with COVID-19 pneumonia confirmed by RT-PCR who were discharged consecutively from the hospital between 5 February 2020 and 10 March 2020 and who underwent serial chest CT scans on schedule were enrolled. The radiological characteristics of all patients were collected and analysed. The total CT score was the sum of non-GGO involvement determined at discharge. Afterwards, all patients underwent chest CT scans during the 1 st , 2 nd , and 3 rd weeks after discharge. Imaging features and distributions were analysed across different time points. Results: : A total of 149 patients who completed all CT scans were evaluated;there were 67 (45.0%) men and 82 (55.0%) women, with a median age of 43 years old (IQR 36-56). The cumulative percentage of complete radiological resolution was 8.1% (12 patients), 41.6% (62), 50.3% (75), and 53% (79) at discharge and during the 1 st , 2 nd , and 3 rd weeks after discharge, respectively. Patients ≤44 years old showed a significantly higher cumulative percentage of complete radiological resolution than patients >44 years old at the 3-week follow-up. The predominant patterns of abnormalities observed at discharge were ground-glass opacity (GGO) (65 [43.6%]), fibrous stripe (45 [30.2%]), and thickening of the adjacent pleura (16 [10.7%]). Lung lesions showed obvious resolution from 2 to 3 weeks after discharge, especially in terms of GGO and fibrous stripe. “Tinted” sign and bronchovascular bundle distortion as two special features were discovered during the evolution. Conclusion: Lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term follow-up with no sequelae. Three weeks after discharge might be the optimal time point for early radiological estimation.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309024

ABSTRACT

Objective: To analyze the differences between clinical evaluation and the detailed imaging features in the time course of lung changes in diverse clinical types. Methods: : 73 patients with COVID-19 pneumonia were retrospectively collected from three institutions in China. Radiographic features, CT score were analyzed and compared between non-emergency group (mild- and common-type) and emergency group (severe- and fatal-type). Results: : In non-emergency group, the disease slowly aggravated within the first two weeks, peaked during the 2nd week (median superimposed involvement CT score: 9.5), while in emergency group, the disease peaked in the 2nd week rapidly, and the superimposed involvement CT score(median: 20) was higher than that in non-emergency group. Both two groups began to decline in the 4th week, and persistence of high levels. In emergency group, the residual lung lesions were mostly reticular (median single reticular CT score: 10) and consolidation (median single consolidation CT score:7). By contrast, most residual lung lesions in non-emergency group were GGO (median single GGO CT score: 7) and reticular (median single reticular CT score: 4). In both non-emergency and emergency groups, GGO pattern was dominant in the first week, and the proportion in emergency group was higher [20 (65%) and (18 (72%), respectively], the consolidation pattern peaked in the second week, which were 9 (32%) and 19 (73%), respectively, reticular pattern became dominant in and after 4 weeks (both over 40%). Conclusion: The disease in non-emergency and emergency group peaks in the second week. In the non-emergency group, the residual lesions are dominated by GGO and reticular, while those in the emergency group are mainly reticular and consolidation. The transiently CT manifestations of emergency and non-emergency follow certain patterns at different time points of the disease course.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323695

ABSTRACT

Knowing the residual and future effect of SARS-CoV-2 on recovered COVID-19 patients is critical for optimized long-term patient management. Recent studies focus on the symptoms and clinical indices of recovered patients, but the pathophysiological change is still unclear. To address this question, we examined the metabolomic profiles of recovered asymptomatic (RA), moderate (RM) and severe and critical (RC) patients without previous underlying diseases discharged from the hospital for 3 months, along with laboratory and CT findings. We found that the serum metabolic profiles in recovered COVID-19 patients still conspicuously differed from that in healthy control (HC), especially in the RM, and RC patients. Additionally, these changes bore close relationship with the function of pulmonary, renal, hepatic, microbial and energetic metabolism and inflammation. These findings suggested that RM and RC patients sustained multi-organ and multi-system damage and these patients should be followed up on regular basis for possible organ and system damage.

8.
J Nat Prod ; 85(2): 327-336, 2022 02 25.
Article in English | MEDLINE | ID: covidwho-1655431

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1-4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Microbial Sensitivity Tests/methods , Phloroglucinol/pharmacology , SARS-CoV-2/drug effects , Terpenes/pharmacology , Chromatography, High Pressure Liquid , Chromatography, Liquid , Crystallography, X-Ray , Drug Delivery Systems , Dryopteris/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Docking Simulation , Molecular Structure , Virtual Reality
9.
Diabetes Metab Res Rev ; 38(4): e3519, 2022 05.
Article in English | MEDLINE | ID: covidwho-1640696

ABSTRACT

AIMS: To explore the association of obesity with the progression and outcome of coronavirus disease 2019 (COVID-19) at the acute period and 5-month follow-up from the perspectives of computed tomography (CT) imaging with artificial intelligence (AI)-based quantitative evaluation, which may help to predict the risk of obese COVID-19 patients progressing to severe and critical disease. MATERIALS AND METHODS: This retrospective cohort enrolled 213 hospitalized COVID-19 patients. Patients were classified into three groups according to their body mass index (BMI): normal weight (from 18.5 to <24 kg/m2 ), overweight (from 24 to <28 kg/m2 ) and obesity (≥28 kg/m2 ). RESULTS: Compared with normal-weight patients, patients with higher BMI were associated with more lung involvements in lung CT examination (lung lesions volume [cm3 ], normal weight vs. overweight vs. obesity; 175.5[34.0-414.9] vs. 261.7[73.3-576.2] vs. 395.8[101.6-1135.6]; p = 0.002), and were more inclined to deterioration at the acute period. At the 5-month follow-up, the lung residual lesion was more serious (residual total lung lesions volume [cm3 ], normal weight vs. overweight vs. obesity; 4.8[0.0-27.4] vs. 10.7[0.0-55.5] vs. 30.1[9.5-91.1]; p = 0.015), and the absorption rates were lower for higher BMI patients (absorption rates of total lung lesions volume [%], normal weight vs. overweight vs. obesity; 99.6[94.0-100.0] vs. 98.9[85.2-100.0] vs. 88.5[66.5-95.2]; p = 0.013). The clinical-plus-AI parameter model was superior to the clinical-only parameter model in the prediction of disease deterioration (areas under the ROC curve, 0.884 vs. 0.794, p < 0.05). CONCLUSIONS: Obesity was associated with severe pneumonia lesions on CT and adverse clinical outcomes. The AI-based model with combinational use of clinical and CT parameters had incremental prognostic value over the clinical parameters alone.


Subject(s)
COVID-19 , Artificial Intelligence , COVID-19/epidemiology , Humans , Intelligence , Obesity/complications , Overweight , Retrospective Studies , Tomography, X-Ray Computed/methods
10.
Eur J Med Chem ; 227: 113966, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1487705

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 µM, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents.


Subject(s)
Antiviral Agents/chemistry , Coronavirus Nucleocapsid Proteins/antagonists & inhibitors , Phenanthridines/chemistry , SARS-CoV-2/metabolism , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Nucleocapsid Proteins/metabolism , Drug Design , Humans , Kinetics , Molecular Docking Simulation , Phenanthridines/metabolism , Phenanthridines/pharmacology , Phenanthridines/therapeutic use , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/metabolism , Protein Binding , Protein Structure, Tertiary , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Vero Cells
11.
Infect Dis Ther ; 11(1): 145-163, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1479541

ABSTRACT

INTRODUCTION: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs). METHODS: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up. RESULTS: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function. CONCLUSIONS: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.

12.
Radiology ; 302(3): 709-719, 2022 03.
Article in English | MEDLINE | ID: covidwho-1450622

ABSTRACT

Background The chest CT manifestations of COVID-19 from hospitalization to convalescence after 1 year are unknown. Purpose To assess chest CT manifestations of COVID-19 up to 1 year after symptom onset. Materials and Methods Patients were enrolled if they were admitted to the hospital because of COVID-19 and underwent CT during hospitalization at two isolation centers between January 27, 2020, and March 31, 2020. In a prospective study, three serial chest CT scans were obtained at approximately 3, 7, and 12 months after symptom onset and were longitudinally analyzed. The total CT score of pulmonary lobe involvement, ranging from 0 to 25, was assessed (score of 1-5 for each lobe). Univariable and multivariable logistic regression analyses were performed to explore independent risk factors for residual CT abnormalities after 1 year. Results A total of 209 study participants (mean age, 49 years ± 13 [standard deviation]; 116 women) were evaluated. CT abnormalities had resolved in 61% of participants (128 of 209) at 3 months and in 75% of participants (156 of 209) at 12 months. Among participants with chest CT abnormalities that had not resolved, there were residual linear opacities in 25 of the 209 participants (12%) and multifocal reticular or cystic lesions in 28 of the 209 participants (13%). Age 50 years or older, lymphopenia, and severe or aggravation of acute respiratory distress syndrome were independent risk factors for residual CT abnormalities at 1 year (odds ratios = 15.9, 18.9, and 43.9, respectively; P < .001 for each comparison). In 53 participants with residual CT abnormalities at 12 months, reticular lesions (41 of 53 participants [77%]) and bronchial dilation (39 of 53 participants [74%]) were observed at discharge and were persistent in 28 (53%) and 24 (45%) of the 53 participants, respectively. Conclusion One year after COVID-19 diagnosis, chest CT scans showed abnormal findings in 53 of the 209 study participants (25%), with 28 of the 209 participants (13%) showing subpleural reticular or cystic lesions. Older participants with severe COVID-19 or acute respiratory distress syndrome were more likely to develop lung sequelae that persisted at 1 year. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Wi et al in this issue.


Subject(s)
COVID-19/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed/methods , Disease Progression , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pneumonia, Viral/virology , Prospective Studies , Risk Factors , SARS-CoV-2
13.
J Inflamm Res ; 14: 4485-4501, 2021.
Article in English | MEDLINE | ID: covidwho-1410010

ABSTRACT

BACKGROUND: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities. METHODS: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants. RESULTS: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions. CONCLUSION: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.

14.
Transl Psychiatry ; 11(1): 307, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1237992

ABSTRACT

This study aimed to explore the associations between cerebral white matter (WM) alterations, mental health status, and metabolism in recovered COVID-19 patients. We included 28 recovered COVID-19 patients and 27 healthy controls between April 2020 and June 2020. Demographic data, the mental health scores, diffusion-tensor imaging (DTI) data, and plasma metabolomics were collected and compared between the two groups. Tract-based spatial statistics and graph theory approaches were used for DTI data analysis. Untargeted metabolomics analysis of the plasma was performed. Correlation analyses were performed between these characteristics. Recovered COVID-19 patients showed decreased fractional anisotropy, increased mean diffusivity and radial diffusivity values in widespread brain regions, and significantly lower global efficiency, longer shortest path length, and less nodal local efficiency in superior occipital gyrus (all, P < 0.05, Bonferroni corrected). Our results also demonstrated significantly different plasma metabolic profiling in recovered COVID-19 patients even at 3 months after their hospital discharge, which was mainly related to purine pathways, amino acids, lipids, and amine metabolism. Certain regions with cerebral WM alterations in the recovered patients showed significant correlations with different metabolites and the mental health scores. We observed multiple alterations in both WM integrity and plasma metabolomics that may explain the deteriorated mental health of recovered COVID-19 patients. These findings may provide potential biomarkers for the mental health evaluation for the recovered COVID-19 patients and potential targets for novel therapeutics.


Subject(s)
COVID-19 , White Matter , Anisotropy , Brain/diagnostic imaging , Humans , Mental Health , Metabolomics , SARS-CoV-2 , White Matter/diagnostic imaging
15.
Virol Sin ; 36(5): 879-889, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1174014

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Mice , Mice, Transgenic , Primates , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Inactivated/immunology
16.
Sci Rep ; 11(1): 417, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1019886

ABSTRACT

This study aims to explore and compare a novel deep learning-based quantification with the conventional semi-quantitative computed tomography (CT) scoring for the serial chest CT scans of COVID-19. 95 patients with confirmed COVID-19 and a total of 465 serial chest CT scans were involved, including 61 moderate patients (moderate group, 319 chest CT scans) and 34 severe patients (severe group, 146 chest CT scans). Conventional CT scoring and deep learning-based quantification were performed for all chest CT scans for two study goals: (1) Correlation between these two estimations; (2) Exploring the dynamic patterns using these two estimations between moderate and severe groups. The Spearman's correlation coefficient between these two estimation methods was 0.920 (p < 0.001). predicted pulmonary involvement (CT score and percent of pulmonary lesions calculated using deep learning-based quantification) increased more rapidly and reached a higher peak on 23rd days from symptom onset in severe group, which reached a peak on 18th days in moderate group with faster absorption of the lesions. The deep learning-based quantification for COVID-19 showed a good correlation with the conventional CT scoring and demonstrated a potential benefit in the estimation of disease severities of COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Deep Learning , Lung/diagnostic imaging , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed/methods
17.
Acta Diabetol ; 58(5): 575-586, 2021 May.
Article in English | MEDLINE | ID: covidwho-1014138

ABSTRACT

AIMS: Increasing evidence suggests that poor glycemic control in diabetic individuals is associated with poor coronavirus disease 2019 (COVID-19) pneumonia outcomes and influences chest computed tomography (CT) manifestations. This study aimed to explore the impact of diabetes mellitus (DM) and glycemic control on chest CT manifestations, acquired using an artificial intelligence (AI)-based quantitative evaluation system, and COVID-19 disease severity and to investigate the association between CT lesions and clinical outcome. METHODS: A total of 126 patients with COVID-19 were enrolled in this retrospective study. According to their clinical history of DM and glycosylated hemoglobin (HbA1c) level, the patients were divided into 3 groups: the non-DM group (Group 1); the well-controlled blood glucose (BG) group, with HbA1c < 7% (Group 2); and the poorly controlled BG group, with HbA1c ≥ 7% (Group 3). The chest CT images were analyzed with an AI-based quantitative evaluation system. Three main quantitative CT features representing the percentage of total lung lesion volume (PLV), percentage of ground-glass opacity volume (PGV) and percentage of consolidation volume (PCV) in bilateral lung fields were used to evaluate the severity of pneumonia lesions. RESULTS: Patients in Group 3 had the highest percentage of severe or critical illness, with 12 (32%) cases, followed by 6 (11%) and 7 (23%) cases in Groups 1 and 2, respectively (p = 0.042). The composite endpoints, including death or using mechanical ventilation or admission to the intensive care unit (ICU), were 3 (5%), 5 (16%) and 10 (26%) in Groups 1, 2 and 3, respectively (p = 0.013). The PLV, PGV and PCV in bilateral lung fields were significantly different among the three groups (all p < 0.001): the median PLVs were 12.5% (Group 3), 3.8% (Group 2) and 2.4% (Group 1); the median PGVs were 10.2% (Group 3), 3.6% (Group 2) and 1.9% (Group 1); and the median PCVs were 1.8% (Group 3), 0.3% (Group 2) and 0.1% (Group 1). In the linear regression analyses, which were adjusted for age, sex, BMI, and comorbidities, HbA1c remained positively associated with PLV (ß = 0.401, p < 0.001), PGV (ß = 0.364, p = 0.001) and PCV (ß = 0.472, p < 0.001); this relationship was also observed between fasting blood glucose (FBG) and the three CT quantitative parameters. In the logistic regression analyses, PLV [OR 1.067 (1.032, 1.103)], PGV [OR 1.076 (1.034, 1.120)] and PCV [OR 1.280 (1.110, 1.476)] levels were independent predictors of the composite endpoints, as well as the areas under the ROC (AUCs) for PLV [AUC 0.796 (0.691, 0.900)], PGV [AUC 0.783 (0.678, 0.889)] and PCV [AUC 0.816 (0.722, 0.911)]; the ORs were still significant for CT lesions after adjusting for age, sex and poorly controlled diabetes. CONCLUSIONS: Increased blood glucose level was correlated with the severity of lung involvement, as evidenced by certain chest CT parameters, and clinical prognosis in diabetic COVID-19 patients. There was a positive correlation between blood glucose level (both HbA1c and FBG) on admission and lung lesions. Moreover, the CT lesion severity by AI quantitative analysis was correlated with clinical outcomes.


Subject(s)
Blood Glucose/analysis , COVID-19/diagnostic imaging , Diabetes Mellitus/epidemiology , Adult , Aged , Artificial Intelligence , COVID-19/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Tomography, X-Ray Computed/methods
18.
Cell Res ; 31(1): 17-24, 2021 01.
Article in English | MEDLINE | ID: covidwho-953056

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Teicoplanin/analogs & derivatives , Animals , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Caco-2 Cells , Chlorocebus aethiops , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Protein Binding/drug effects , Teicoplanin/pharmacokinetics , Teicoplanin/pharmacology , Vero Cells
19.
Int J Med Sci ; 17(17): 2653-2662, 2020.
Article in English | MEDLINE | ID: covidwho-902899

ABSTRACT

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung/diagnostic imaging , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia/diagnostic imaging , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , China , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Female , Humans , Longitudinal Studies , Lung/physiopathology , Lung/virology , Male , Middle Aged , Pneumonia/physiopathology , Pneumonia/virology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2 , Tomography, X-Ray Computed
20.
Eur J Cardiothorac Surg ; 58(4): 858-860, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-780369

ABSTRACT

This report describes a patient with COVID-19 who developed spontaneous pneumothorax and subpleural bullae during the course of the infection. Consecutive chest computed tomography images indicated that COVID-19-associated pneumonia had damaged the subpleural alveoli and distal bronchus. Coughing might have induced a sudden increase in intra-alveolar pressure, leading to the rupture of the subpleural alveoli and distal bronchus and resulting in spontaneous pneumothorax and subpleural bullae. At the 92-day follow-up, the pneumothorax and subpleural bullae had completely resolved, which indicated that these complications had self-limiting features.


Subject(s)
Betacoronavirus , Blister/virology , Coronavirus Infections/diagnosis , Pleural Diseases/virology , Pneumonia, Viral/diagnosis , Pneumothorax/virology , Adult , Betacoronavirus/isolation & purification , Blister/diagnostic imaging , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Humans , Male , Pandemics , Pleural Diseases/diagnostic imaging , Pneumonia, Viral/complications , Pneumothorax/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed
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