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1.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333831

ABSTRACT

BACKGROUND: Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. METHODS: We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. RESULTS: At 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69;95% confidence interval [CI], 0.43 to 1.10;p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22;95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59;95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52;95%-CI, 0.09 to 2.85). CONCLUSIONS: In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days. Trial registration numbers: NCT04362085 ;NCT04444700.

2.
Blood ; 138(SUPPL 1):3525, 2021.
Article in English | EMBASE | ID: covidwho-1770434

ABSTRACT

Background - The WINDOW-1 regimen introduced first-line ibrutinib with rituximab (IR) followed by 4 cycles of R-HCVAD for younger mantle cell lymphoma (MCL) patients (pts) demonstrating 90% CR on IR alone and we aimed to improve the CR rate with the addition of venetoclax. We therefore investigated the efficacy and safety of IR and venetoclax (IRV) followed by risk-stratified observation or short course R-HCVAD/MTX-ARA-C as consolidation in previously untreated young patients with mantle cell lymphoma (MCL). Our aim was to use a triplet chemotherapy-free induction to reduce the toxicity, complications and minimize chemotherapy exposure in MCL pts. Methods - We enrolled 50 previously untreated pts in this single institution, single arm, phase II clinical trial - NCT03710772. Pts received IR induction (Part-1) for initial 4 cycles. Pts were restaged at cycle 4 and received IRV for up to eight cycles (Cycle 5 to Cycle 12) starting with ramp up venetoclax dosing in Cycle 5. All pts who achieved CR prior to cycle 12 continued to receive IRV for 4 cycles (maximum 12 cycles) and then moved to part 2. Pts were stratified into three disease risk groups: high, moderate and low risk categories from the baseline data for assignment to R-HCVAD/MTX-ARA-C as consolidation in part 2 (4 cycles, 2 cycles, or no chemotherapy for high, medium and low risk pts respectively). Briefly, low risk pts were those with Ki-67 ≤30%, largest tumor mass <3 cm, low MIPI score and no features of high risk disease (Ki-67 ≥50%, mutations in the TP53, NSD2 or in NOTCH genes, complex karyotype or del17p, MYC positive, or largest tumor diameter >5 cm or blastoid/pleomorphic histology or if they remain in PR after 12 cycles of part 1. Medium risk are pts which did not belong to low or high-risk category. Those who experienced progression on part 1 went to part 2 and get 4 cycles of part 2. Patient were taken off protocol but not off study, if they remained in PR after 4 cycles of chemotherapy, these patients were followed up for time to next treatment and progression free survival on subsequent therapies. After part 2 consolidation, all pts received 2 years of IRV maintenance. The primary objective was to assess CR rates after IRV induction. Adverse events were coded as per CTCAE version 4. Molecular studies are being performed. Results - Among the 50 pts, the median age was 57 years (range - 35-65). There were 20 pts in high-risk group, 20 pts in intermediate-risk group and 10 pts in low-risk group. High Ki-67 (≥30%) in 18/50 (36%) pts. Eighteen (36%) had high and intermediate risk simplified MIPI scores. Six (12%) pts had aggressive MCL (blastoid/pleomorphic). Among the 24 TP53 evaluable pts, eight pts (33%) had TP53 aberrations (mutated and/or TP53 deletion by FISH). Forty-eight pts received IRV. Best response to IRV was 96% and CR of 92%. After part 2, the best ORR remained unaltered, 96% (92% CR and 4% PR). The median number of cycles of triplet IRV to reach best response was 8 cycles (range 2-12). Fifteen pts (30%) did not receive part 2 chemotherapy, two pts (4%) received 1 cycle, 16 pts (32%) 2 cycles and 13 pts (26%) got 4 cycles of chemotherapy. With a median follow up of 24 months, the median PFS and OS were not reached (2 year 92% and 90% respectively). The median PFS and OS was not reached and not significantly different in pts with high and low Ki-67% or with/without TP53 aberrations or among pts with low, medium or high-risk categories. The median PFS and OS was inferior in blastoid/pleomorphic MCL pts compared to classic MCL pts (p=0.01 and 0.03 respectively). Thirteen pts (26%) came off study - 5 for adverse events, 3 for on study deaths, and 2 for patient choice, 2 patients lost to follow up and one for disease progression. Overall, 5 pts died (3 on trial and 2 pts died off study, one due to progressive disease and another due to COVID pneumonia). Grade 3-4 toxicities on part 1 were 10% myelosuppression and 10% each with fatigue, myalgia and rashes and 3% mucositis. One pt developed grade 3 atrial flutter on part 1. None had grade 3-4 bleeding/bruising. Conclusions - Chemotherapy-free induction with IRV induced durable and deep responses in young MCL pts in the frontline setting. WINDOW-2 approach suggests that pts with low risk MCL do not need chemotherapy but further follow up is warranted. This combined modality treatment approach significantly improves outcomes of young MCL pts across all risk groups. Detailed molecular analyses will be reported. (Figure Presented).

3.
Journal of Geophysical Research-Atmospheres ; 127(3):14, 2022.
Article in English | Web of Science | ID: covidwho-1747263

ABSTRACT

Unexpectedly frequent severe haze episodes were observed in Beijing during February-March in 2021 after two phases of clean air action plan (2013-2020), yet the causes remained unclear. Here, we conducted real-time fine particle (PM2.5) composition measurements during January-March in 2021 using a time-of-flight aerosol chemical speciation monitor and an aethalometer and compared with those during the coronavirus disease (COVID-19) period in 2020. Our results showed ubiquitously elevated concentrations of chloride, black carbon (BC), and primary organic aerosol (POA) in 2021, suggesting increased primary emissions during the post-COVID-19 period. By using the machine learning-based random forest (RF) algorithm, we found largely different responses of aerosol changes to meteorology in different months. After decoupling the effects of meteorology, the PM2.5 changes from 2020 to 2021 were reduced from -35.6% to -29.0% in January, -24.1% to -4.5% in February, and +92.6% to +34.2% in March, respectively. Our results demonstrate the dominant roles of stagnant meteorology and secondary production in the formation of severe haze episodes in March 2021. In particular, we found that the compositions of observed and deweathered PM2.5 were fairly similar between 2020 and 2021, and the ratios of secondary OA to secondary inorganic aerosols were close. Our study indicates that decoupling the influence of meteorological conditions is of great importance for better evaluation of mitigating strategies of air pollution due to the large impact of meteorology on the changes in PM2.5 species particularly in a short period.

4.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-329156

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has killed millions of people worldwide. The current crisis has created an unprecedented demand for rapid test of SARS-CoV-2 infection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a fast and convenient method to amplify and identify the transcripts of a targeted pathogen. However, the sensitivity and specificity of RT-LAMP were generally regarded as inferior when compared with the gold standard RT-qPCR. To address this issue, we combined bioinformatic and experimental analyses to improve the assay performance for COVID-19 diagnosis. First, we developed an improved algorithm to design LAMP primers targeting the nucleocapsid (N), membrane (M), and spike (S) genes of SARS-CoV-2. Next, we rigorously validated these new assays for their efficacy and specificity. Further, we demonstrated that multiplexed RT-LAMP assays could directly detect as low as a few copies of SARS-CoV-2 RNA in saliva, without the need of RNA isolation. Importantly, further testing using saliva samples from COVID-19 patients indicated that the new RT-LAMP assays were in total agreement in sensitivity and specificity with standard RT-qPCR. In summary, our new LAMP primer design algorithm along with the validated assays provide a fast and reliable method for the diagnosis of COVID-19 cases.

5.
2021 IEEE Canadian Conference on Electrical and Computer Engineering, CCECE 2021 ; 2021-September, 2021.
Article in English | Scopus | ID: covidwho-1511201

ABSTRACT

Our study aims to investigate the best performing Convolutional Neural Networks (CNN) suitable for COVID-19 detection on Chest X-Ray (CXR) images. We applied five state-of-art CNN models in this study: DarkNet-19, ResNet-101, SqueezeNet, VGG-16, and VGG-19. These CNN models were pre-trained with natural images for classification. Therefore, we used transfer learning to modify the fully connected layer and output layer for a binary classification between COVID-19 and normal lungs. The models were trained using our combined dataset of CXR images obtained from the public domain, COVIDx, and private domain, University of Malaya (UM). The CXR images were pre-processed with reflection along the horizontal and vertical axis before being fed into the CNN models. Then another combined dataset from both COVIDx and UM was used to test the performance of the models. The numbers of correctly and wrongly predicted classes were tallied and represented with a confusion matrix. Then, the specificity, sensitivity, precision, F1-score, and accuracy were measured to evaluate the performance of each model. Our study demonstrated an accuracy above 90% for all five models. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize the significant activation regions that contributed to the model's decision. We have also applied the COVID-Net-CXR-Large model to our combined dataset for testing to evaluate its performance in multiclass classification. The current CNN models require further improvement and modification before they can be applied clinically as a secondary tool for the diagnosis of COVID-19 cases. © 2021 IEEE.

6.
Iranian Journal of Radiology ; 18(3), 2021.
Article in English | EMBASE | ID: covidwho-1377096

ABSTRACT

Background: The novel coronavirus disease 2019 (COVID-19) has become a global public health emergency. Computed tomography (CT) offers valuable clues to the diagnosis of COVID-19. However, little is known about the correlation between dynamic changes of CT scores and therapeutic response in the course of COVID-19. Objectives: To describe the temporal changes of CT findings and characterize the time window of disease progression on the follow-up CT scans of patients with COVID-19. Patients and Methods: In this historical cohort study performed in Shanghai, China, the follow-up chest CT images of 91 patients with COVID-19 with different therapeutic responses were reviewed in multiple centers, with an emphasis on characterizing the changing trend of CT scores for lung lesions at 13-15 days after the symptom onset and thereafter. The CT score curve patterns were categorized into type 1 (characterized by an increase to the peak level, followed by a decrease), type 2 (characterized by a steady change without an obvious peak), and type 3 (characterized by a progressive increase). Results: The CT scores of the progression group (n = 9) with a longer time to the peak were significantly higher than those of the non-progression group (n = 82) on the first day and days 13-15 (P < 0.05), except for the median CT scores before days 13-15. The CT curve type 1 and type 2 were commonly observed in the non-progression group (63.4% and 36.6%, respectively), while type 3 was more common in the progression group (88.9%). Conclusion: Most patients with COVID-19 show favorable responses to clinical treatments in Shanghai. Thirteen to fifteen days after the symptom onset can be considered as a turning point for the therapeutic response. The CT curve type 3 usually represents a poor response. The CT scores of patients with different therapeutic responses may overlap before days 13-15. The changing trend of longitudinal CT scores may contribute to the prediction of disease progression.

7.
Medical Journal of Wuhan University ; 42(4):594-598, 2021.
Article in Chinese | Scopus | ID: covidwho-1299712

ABSTRACT

Objective: To evaluate the clinical efficacy of Lopinavir-Ritonavir combined with interferon alpha on coronavirus disease 2019 (COVID-19). Methods: A prospective and real-world observational clinical research was conducted on COVID-19 cases who were admitted to the Renmin Hospital of Wuhan University from January 25, 2020 to February 12, 2020. Of the 109 cases involved, 58 cases were treated with interferon alpha (group A), while 58 cases were treated with Lopinavir-Ritonavir combined with interferon alpha (group B). The recent outcomes were compared between the two groups by Kruskal Wallis test or Chi square test. Results: The baseline data of the two groups were basically the same. On the 7th day after treatment, the lung inflammation in group B was higher than in group A, and the leukocyte count and neutrophil count in the normal range increased as compared with the baseline value in group B. On the 14th day after treatment, the leukocyte count, lymphocyte count, CD4/CD8 cell count increased as compared with the baseline value, while CRP decreased from baseline in the B group, with statistically significant differnce. Conclusion: Lopinavir-Ritonavir combined with interferon alpha can accelerate the improvement of pulmonary inflammation, and increase the levels of immune cells in COVID-19 patients. © 2021, Editorial Board of Medical Journal of Wuhan University. All right reserved.

8.
Cardiovascular Innovations and Applications ; 5(3):165-172, 2021.
Article in English | Web of Science | ID: covidwho-1154911

ABSTRACT

Background: Since early December 2019, coronavirus disease 2019 (COVID-19) has emerged as a global pandemic and public health crisis. This study aims to explore the relationship between cardiac injury and inflammatory biomarkers in patients with severe COVID-19. Methods: We collected data on 91 patients with a confirmed diagnosis of severe COVID-19 from February 8 to March 31, 2020. Demographic characteristics, clinical data, and in-hospital outcomes were compared. The relationship between cardiac injury and inflammatory biomarkers was analyzed. Logistic regression was used to explore the independent risk factors for cardiac injury. Results: The mean age of all patients was 61 years +/- 14 years. About half of the patients were male. Hypertension and coronary heart disease were more common in the cardiac injury group. The levels of inflammatory biomarkers in patients who experienced cardiac injury were generally higher than the levels of those without cardiac injury, including interleukin-6, interleukin-2 receptor (IL-2R), procalcitonin, and high-sensitivity C-reactive protein. There were positive correlations between the levels of high-sensitivity troponin I and N-terminal prohormone of brain natriuretic peptide and the levels of inflammatory biomarkers. Logistic regression shows that IL-2R (odds ratio 1.001, 95% confidence interval 1.000-1.002, P = 0.045) and comorbidities (odds ratio 4.909, 95% confidence interval 1.231-19.579, P = 0.024) are independent risk factors for cardiac injury in patients with severe COVID-19. Conclusion: High levels of inflammatory biomarkers are associated with higher risk of cardiac injury in patients with severe COVID-19. IL-2R and comorbidities are predictors of cardiac injury.

9.
Hong Kong Med J ; 28(1): 64-72, 2022 02.
Article in English | MEDLINE | ID: covidwho-1058643

ABSTRACT

Intensive care is expensive, and the numbers of intensive care unit (ICU) beds and trained specialist medical staff able to provide services in Hong Kong are limited. The most recent increase in coronavirus disease 2019 (COVID-19) infections over July to August 2020 resulted in more than 100 new cases per day for a prolonged period. The increased numbers of critically ill patients requiring ICU admission posed a capacity challenge to ICUs across the territory, and it may be reasonably anticipated that should a substantially larger outbreak occur, ICU services will be overwhelmed. Therefore, a transparent and fair prioritisation process for decisions regarding patient ICU admission is urgently required. This triage tool is built on the foundation of the existing guidelines and framework for admission, discharge, and triage that inform routine clinical practice in Hospital Authority ICUs, with the aim of achieving the greatest benefit for the greatest number of patients from the available ICU resources. This COVID-19 Crisis Triage Tool is expected to provide structured guidance to frontline doctors on how to make triage decisions should ICU resources become overwhelmed by patients requiring ICU care, particularly during the current COVID-19 pandemic. The triage tool takes the form of a detailed decision aid algorithm based on a combination of established prognostic scores, and it should increase objectivity and transparency in triage decision making and enhance decision-making consistency between doctors within and across ICUs in Hong Kong. However, it remains an aid rather than a complete substitute for the carefully considered judgement of an experienced intensive care clinician.


Subject(s)
COVID-19 , Hospitalization , Triage , Adult , COVID-19/epidemiology , Disease Outbreaks , Hong Kong/epidemiology , Humans , Intensive Care Units , Pandemics , SARS-CoV-2 , Triage/methods
10.
Clin Exp Immunol ; 201(1): 76-84, 2020 07.
Article in English | MEDLINE | ID: covidwho-628822

ABSTRACT

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Interleukin-2 Receptor alpha Subunit/blood , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , T-Lymphocytes/virology , Aged , Aged, 80 and over , Betacoronavirus/immunology , Biomarkers/blood , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19 , China/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Disease Progression , Female , Ferritins/blood , Ferritins/immunology , Humans , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-6/blood , Interleukin-6/immunology , Interleukin-8/blood , Interleukin-8/immunology , Leukocyte Count , Male , Middle Aged , Neutrophils/immunology , Neutrophils/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Procalcitonin/blood , Procalcitonin/immunology , Prognosis , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology
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