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1.
Molecules ; 27(19)2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-2066284

ABSTRACT

Three unique 5,6-seco-hexahydrodibenzopyrans (seco-HHDBP) machaeridiols A-C, reported previously from Machaerium Pers., have displayed potent activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium, and E. faecalis (VRE). In order to enrich the pipeline of natural product-derived antimicrobial compounds, a series of novel machaeridiol-based analogs (1-17) were prepared by coupling stemofuran, pinosylvin, and resveratrol legends with monoterpene units R-(-)-α-phellandrene, (-)-p-mentha-2,8-diene-1-ol, and geraniol, and their inhibitory activities were profiled against MRSA ATCC 1708, VRE ATCC 700221, and cancer signaling pathways. Compounds 5 and 11 showed strong in vitro activities with MIC values of 2.5 µg/mL and 1.25 µg/mL against MRSA, respectively, and 2.50 µg/mL against VRE, while geranyl analog 14 was found to be moderately active (MIC 5 µg/mL). The reduction of the double bonds of the monoterpene unit of compound 5 resulted in 17, which had the same antibacterial potency (MIC 1.25 µg/mL and 2.50 µg/mL) as its parent, 5. Furthermore, a combination study between seco-HHDBP 17 and HHDBP machaeriol C displayed a synergistic effect with a fractional inhibitory concentrations (FIC) value of 0.5 against MRSA, showing a four-fold decrease in the MIC values of both 17 and machaeriol C, while no such effect was observed between vancomycin and 17. Compounds 11 and 17 were further tested in vivo against nosocomial MRSA at a single intranasal dose of 30 mg/kg in a murine model, and both compounds were not efficacious under these conditions. Finally, compounds 1-17 were profiled against a panel of luciferase genes that assessed the activity of complex cancer-related signaling pathways (i.e., transcription factors) using T98G glioblastoma multiforme cells. Among the compounds tested, the geranyl-substituted analog 14 exhibited strong inhibition against several signaling pathways, notably Smad, Myc, and Notch, with IC50 values of 2.17 µM, 1.86 µM, and 2.15 µM, respectively. In contrast, the anti-MRSA actives 5 and 17 were found to be inactive (IC50 > 20 µM) across the panel of these cancer-signaling pathways.


Subject(s)
Anti-Infective Agents , Biological Products , Methicillin-Resistant Staphylococcus aureus , Neoplasms , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Biological Products/pharmacology , Luciferases , Mice , Microbial Sensitivity Tests , Monoterpenes/pharmacology , Resveratrol/pharmacology , Signal Transduction , Transcription Factors , Vancomycin/pharmacology
2.
Clinical eHealth ; 2022.
Article in English | ScienceDirect | ID: covidwho-1936135

ABSTRACT

Background The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan University (NCT04275947, B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. The effects of different diagnostic factors were ranked based on the results from a single factor analysis, with 0.05 as the significance level for factor inclusion and 0.1 as the significance level for factor exclusion. Independent variables were selected by the step-forward multivariate logistic regression analysis to obtain the probability model. Findings We applied the statistical method of a multivariate regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are accessible. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results.

3.
BMJ : British Medical Journal (Online) ; 368, 2020.
Article in English | ProQuest Central | ID: covidwho-1837197

ABSTRACT

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

4.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323649

ABSTRACT

Background: : COVID-19 causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation in COVID-19 has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation in COVID-19. Methods: : In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines. Results: : Among 225 patients with confirmed COVID-19, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein (hsCRP) as well as interleukin (IL)-6, IL-8, tumour necrosis factor α (TNF-α), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%). Conclusion: Excessive systemic inflammation was correlated highly with poor clinical outcomes in COVID-19, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation. Trial registration: This is a retrospective observational study without a trial registration number.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316849

ABSTRACT

Background: Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19.MethodsIn this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Mar. 08, 2020. Clinical, demographic, and laboratory data were collected.Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS- CoV-2 with regard to metabolism pathways.ResultsA total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors were D- Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p=.005), immune-related metabolic index (6.42 [95% CI 2.66 - 15.48], p<.001), and neutrophil-to-lymphocyte ratio (1.08 [95% 1.03 - 1.13], p<.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI0.17 - 0.51], p<.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56 - 75.72], p<0.001), fatty acid (15.61 [95% CI 6.66 - 36.6], p<0.001), and pyruvate (12.86 [95% CI 5.85 - 28.28], p<0.001) showed a consistently lower flux in the surviving versus the deceased subgroup. This may reflect a key pathogenesis of COVID-19 infection.ConclusionAlthough a high mortality has been reported for elderly patients with COVID-19, in this analysis, several factors such as interferon atmotherapy and activity of metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, the survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Deregulation of metabolic pathways revealed in this study may aid in the drug development against COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309524

ABSTRACT

Background: :The emergence of Corona Virus Disease 2019 (COVID-19) in Wuhan, China at the end of 2019 is a major public health issue, causing to a large global outbreak. However, the information regarding the clinical characteristic and progression of severe and critically ill patients with COVID-19 is scarce. Methods: We conducted a single-center, retrospective, observational study and enrolled 126 severe and critically ill adult patients who were admitted to the intensive care unit (ICU) of Tongji hospital, between Feb 1 and Feb 20, 2020. Results: Of 126 patients, 85 patients with the positive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included. The mean age of 85 patients was 68.3 (SD 10.5) years. More than half were men, 55 (62.4%) had chronic illness. 57 (66.3%) patients had died before Feb 28, 2020. the median duration from onset of illness to death, hospitalization to death and ICU admission to death were 22 (17.0-26.0) days, 9.0 (6.0-13.0) days and 5.0 (2.0-6.0) days, respectively. Compared with survivors, non-survivors were more likely old (69.6 [SD 10.22] vs 65.6 [10.9]). Furthermore, the non-survivors had higher white blood cell (WBC) and neutrophil count, neutrophil percentage, high-sensitive C-reactive protein (hs-CRP) and lower lymphocyte and platelet count, lymphocyte percentage and albumin. Notably, arbidol may improve the survival of severe and critically ill patients. Conclusions: Our study reveals the non-survivors had worse blood routine and other clinical monitors. Additionally, arbidol may play useful role in the survival of severe and critically ill patients, which needs further validation.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325194

ABSTRACT

Background: Current information is not enough to recognize the risk factors of clinical deterioration and to make medical decisions in COVID-19 patients. Methods: : A retrospective study was performed, with collecting data from medical records of COVID-19 patients in three designated hospitals from January 8, 2020 to May 6, 2020. Clinical data were analyzed between the deteriorated and the non-deteriorated patients, which was defined as either a increase of 2 categories on the modified 6-category ordinal scale, or a decline of PaO 2 -to-FIO 2 ratio more than 100mmHg. Results: : Total 238 patients with COVID-19 were selected, where 31 were deteriorated and 207 were non-deteriorated. In the deterioration group, the case fatality rate was up to 41.9%. Compared with non-deteriorated patients, the deteriorated were older (65.8[IQR 54.3-72.3] vs 54.4[41.0-66.1], p=0.004) and were more likely to have chronic medical illnesses (17[54.8%]) vs 92[44.4%]). Multivariable regression showed that three variables, neutrophil-lymphocyte ratio (NLR)≥3.66 (OR, 9.85;95% CI, 1.68-57.57), hyponatremia (OR, 8.35;95% CI, 1.74-40.16), and presence of ground-glass opacities with consolidation (OR, 5.84;95% CI, 1.24-27.49) were associated with increased odds of clinical deterioration. The variable that inspiring air or traditional oxygen therapy only within 72 hours after admission, indicated a decreased odd of illness progression (OR, 0.075;95% CI, 0.012–0.465). Conclusions: : COVID-19 patients with clinical deterioration had more common extra-pulmonary organ impair in early stage and high case fatality rate. Three factors, NLR ≥3.66, hyponatremia and presence of ground-glass opacities with consolidation were determined as high risk factors in deterioration.

9.
Ther Adv Chronic Dis ; 12: 20406223211041924, 2021.
Article in English | MEDLINE | ID: covidwho-1398819

ABSTRACT

BACKGROUND: A novel coronavirus disease 2019 (COVID-19) has caused outbreaks worldwide, and the number of cases is rapidly increasing through human-to-human transmission. Because of the greater transmission capacity and possible subsequent multi-organ damage caused by the virus, it is crucial to understand precisely and manage COVID-19 patients. However, the underlying differences in the clinical features of COVID-19 with and without comorbidities are not fully understood. AIM: The objective of this study was to identify the clinical features of COVID-19 patients with and without complications to guide treatment and predict the prognosis. METHOD: We collected the clinical characteristics of COVID-19 patients with and without different complications, including hypertension, cardiovascular disease and diabetes. Next, we performed a baseline comparison of each index and traced the dynamic changes in these factors during hospitalization to explore the potential associations. RESULT: A clinical index of differential expression was used for the regression to select top-ranking factors. The top-ranking clinical characteristics varied in each subgroup, such as indices of liver function, renal function and inflammatory markers. Among them, the indices of renal function were highly ranked in all subgroups and displayed significant differences during hospitalization. CONCLUSION: Organ functions of COVID-19 patients, particularly renal function, should be cautiously taken care of during management and might be a crucial factor for a poor prognosis of these patients with complications.

10.
Front Med ; 15(5): 704-717, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1204959

ABSTRACT

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.


Subject(s)
COVID-19 , Humans , Medicine, Chinese Traditional , Research , SARS-CoV-2 , Treatment Outcome
11.
Front Med (Lausanne) ; 8: 582764, 2021.
Article in English | MEDLINE | ID: covidwho-1154222

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) has swept through the world at a tremendous speed, and there is still limited data available on the treatment for COVID-19. The mortality of severely and critically ill COVID-19 patients in the Optical Valley Branch of Tongji Hospital was low. We aimed to analyze the available treatment strategies to reduce mortality. Methods: In this retrospective, single-center study, we included 1,106 COVID-19 patients admitted to the Optical Valley Branch of Tongji Hospital from February 9 to March 9, 2020. Cases were analyzed for demographic and clinical features, laboratory data, and treatment methods. Outcomes were followed up until March 29, 2020. Results: Inflammation-related indices (hs-CRP, ESR, serum ferritin, and procalcitonin) were significantly higher in severe and critically ill patients than those in moderate patients. The levels of cytokines, including IL-6, IL2R, IL-8, and TNF-α, were also higher in the critical patients. Incidence of acute respiratory distress syndrome (ARDS) in the severely and critically ill group was 23.0% (99/431). Sixty-one patients underwent invasive mechanical ventilation. The correlation between SpO2/FiO2 and PaO2/FiO2 was confirmed, and the cut-off value of SpO2/FiO2 related to survival was 134.43. The mortality of patients with low SpO2/FiO2 (<134.43) at intubation was higher than that of patients with high SpO2/FiO2 (>134.43) (72.7 vs. 33.3%). Among critical patients, the application rates of glucocorticoid therapy, continuous renal replacement therapy (CRRT), and anticoagulation treatment reached 55.2% (238/431), 7.2% (31/431), and 37.1% (160/431), respectively. Among the intubated patients, the application rates of glucocorticoid therapy, CRRT, and anticoagulation treatment were respectively 77.0% (47/61), 54.1% (33/61), and 98.4% (60/61). Conclusion: No vaccines or specific antiviral drugs for COVID-19 have been shown to be sufficiently safe and effective to date. Comprehensive treatment including ventilatory support, multiple organ function preservation, glucocorticoid use, renal replacement therapy, anticoagulation, and restrictive fluid management was the main treatment strategy. Early recognition and intervention, multidisciplinary collaboration, multi-organ function support, and personalized treatment might be the key for reducing mortality.

12.
Mediators Inflamm ; 2021: 8812304, 2021.
Article in English | MEDLINE | ID: covidwho-1145381

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.


Subject(s)
COVID-19/blood , COVID-19/complications , Hyperglycemia/blood , Hyperglycemia/complications , Inflammation/blood , Inflammation/complications , SARS-CoV-2 , Aged , Blood Glucose/metabolism , Blood Sedimentation , C-Reactive Protein/metabolism , COVID-19/epidemiology , China/epidemiology , Diabetes Complications/blood , Female , Humans , Leukocyte Count , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , Severity of Illness Index
13.
Int J Biol Sci ; 17(2): 539-548, 2021.
Article in English | MEDLINE | ID: covidwho-1090199

ABSTRACT

Rationale: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. A classifier combining chest X-ray (CXR) with clinical features may serve as a rapid screening approach. Methods: The study included 512 patients with COVID-19 and 106 with influenza A/B pneumonia. A deep neural network (DNN) was applied, and deep features derived from CXR and clinical findings formed fused features for diagnosis prediction. Results: The clinical features of COVID-19 and influenza showed different patterns. Patients with COVID-19 experienced less fever, more diarrhea, and more salient hypercoagulability. Classifiers constructed using the clinical features or CXR had an area under the receiver operating curve (AUC) of 0.909 and 0.919, respectively. The diagnostic efficacy of the classifier combining the clinical features and CXR was dramatically improved and the AUC was 0.952 with 91.5% sensitivity and 81.2% specificity. Moreover, combined classifier was functional in both severe and non-serve COVID-19, with an AUC of 0.971 with 96.9% sensitivity in non-severe cases, which was on par with the computed tomography (CT)-based classifier, but had relatively inferior efficacy in severe cases compared to CT. In extension, we performed a reader study involving three experienced pulmonary physicians, artificial intelligence (AI) system demonstrated superiority in turn-around time and diagnostic accuracy compared with experienced pulmonary physicians. Conclusions: The classifier constructed using clinical and CXR features is efficient, economical, and radiation safe for distinguishing COVID-19 from influenza A/B pneumonia, serving as an ideal rapid screening tool during the COVID-19 pandemic.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnostic imaging , Influenza, Human/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Radiography, Thoracic , Aged , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/virology , Deep Learning , Diagnosis, Differential , Humans , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/physiopathology , Influenza, Human/virology , Male , Middle Aged , Pandemics , Pneumonia , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
15.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1066782

ABSTRACT

The recovery process of COVID-19 patients is unclear. Some recovered patients complain of continued shortness of breath. Vasculopathy has been reported in COVID-19, stressing the importance of probing pulmonary microstructure and function at the alveolar-capillary interface. While computed tomography (CT) detects structural abnormalities, little is known about the impact of disease on lung function. 129Xe magnetic resonance imaging (MRI) is a technique uniquely capable of assessing ventilation, microstructure, and gas exchange. Using 129Xe MRI, we found that COVID-19 patients show a higher rate of ventilation defects (5.9% versus 3.7%), unchanged microstructure, and longer gas-blood exchange time (43.5 ms versus 32.5 ms) compared with healthy individuals. These findings suggest that regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished. This study establishes the feasibility of localized lung function measurements in COVID-19 patients and their potential usefulness as a supplement to structural imaging.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/physiopathology , Lung/physiopathology , Pulmonary Gas Exchange , Adult , Female , Humans , Lung/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Patient Discharge , Respiratory Function Tests , Tomography, X-Ray Computed , Xenon Isotopes
16.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1066781

ABSTRACT

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.


Subject(s)
COVID-19/metabolism , DNA-Binding Proteins/metabolism , Macrophages/metabolism , Pulmonary Fibrosis/metabolism , Animals , Bleomycin/pharmacology , Carcinoma, Non-Small-Cell Lung/metabolism , Fibrosis , Gene Expression Profiling , Gene Expression Regulation , Humans , Liposomes/chemistry , Lung Diseases, Interstitial/metabolism , Lung Neoplasms/metabolism , Macrophages/virology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Pulmonary Fibrosis/virology , RNA, Small Interfering/metabolism , Scleroderma, Systemic/metabolism , Signal Transduction , Transforming Growth Factor beta1/metabolism
18.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5379

ABSTRACT

A review. To standard the clin. diagnosis and treatment of severe and critical novel coronavirus pneumonia (COVID-19), improve the treatment and reduce the fatality rate, we develop the diagnosis and treatment plan for severe and critical novel coronavirus pneumonia, including diagnostic criteria, early warning indicators, treatment process and nursing plan, based on the National Health Committee of China published novel coronavirus pneumonia diagnosis and treatment plan (trial version 6) and severe and critical novel coronavirus pneumonia diagnosis and treatment plan (trial version 1), combined with the practice of early medical treatment experience, to provide the reference for counterparts.

19.
Ann Clin Microbiol Antimicrob ; 20(1): 3, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1013151

ABSTRACT

BACKGROUND AND OBJECTIVE: Little is yet known whether pathogenesis of COVID-19 is different between young and elder patients. Our study aimed to investigate the clinical characteristics and provide predictors of mortality for young adults with severe COVID-19. METHODS: A total of 77 young adults with confirmed severe COVID-19 were recruited retrospectively at Tongji Hospital. Clinical characteristics, laboratory findings, treatment and outcomes were obtained from electronic medical records. The prognostic effects of variables were analyzed using logistic regression model. RESULTS: In this retrospective cohort, non-survivors showed higher incidence of dyspnea and co-existing laboratory abnormalities, compared with young survivals in severe COVID-19. Multivariate logistic regression analysis showed that lymphopenia, elevated level of d-dimer, hypersensitive cardiac troponin I (hs-CTnI) and high sensitivity C-reactive protein (hs-CRP) were independent predictors of mortality in young adults with severe COVID-19. Further analysis showed that severely young adults with two or more factors abnormalities above would be more prone to death. The similar predictive effect of above four factors had been observed in all-age patients with severe COVID-19. CONCLUSION: Lymphopenia, elevated level of d-dimer, hs-CTnI and hs-CRP predicted clinical outcomes of young adults with severe COVID-19.


Subject(s)
COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , China/epidemiology , Cohort Studies , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Pandemics , Regression Analysis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Treatment Outcome , Young Adult
20.
J Mol Diagn ; 23(1): 10-18, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-988428

ABSTRACT

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) have not been well studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step RT droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48 of 52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53 of 87). One-step RT-ddPCR was tested with a 3.03% false-positive rate and lower 50% confidence interval of detection at 54.026 copies/mL plasma. There was no reduction in the blood viral load in all critical patients, whereas the general and severe patients exhibited a similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in their general and severe counterparts. Among the 52 study patients, 30 (58%) were discharged from the hospital. Among half of the 30 discharged patients, blood viral load remained positive, of which 76.9% (10 of 13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had evidence of infection. Quantitative determination of the blood viral test is of great clinical significance in the management of patients with coronavirus disease 2019.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Severity of Illness Index , Viral Load/methods , Viremia/blood , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/pathology , Female , Humans , Male , Middle Aged , Oropharynx/virology , Prospective Studies , Real-Time Polymerase Chain Reaction , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Treatment Outcome , Viremia/mortality
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