ABSTRACT
The article's objective was to assess the clinical diagnostic utility of plasma levels of CRP, PCT, and IL-6 in individuals with COVID-19 both alone and in combination. Results showed that according to the ROC curve, PCT and CRP were highly valuable in the diagnosis of COVID-19, and CRP was most valuable in the evaluation of patients with severe and critical COVID-19. The combined detection of the three indexes might increase the evaluation's effectiveness. When evaluating COVID-19 patients who were in severe condition, IL-6 demonstrated a strong predictive value. Therefore, combining the three indicators may increase the diagnostic efficiency and provide crucial reference values for the clinical diagnosis and treatment of COVID-19. CRP, PCT, and IL-6 levels may be potential biomarkers for the diagnosis of COVID-19 and can be used to determine the severity of COVID-19.
ABSTRACT
The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development.
ABSTRACT
Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids in Coptis chinensis Franch. (CCFIAs) exerted a multitude of biological activities such as anti-inflammatory, antioxidant, antibacterial, and immunomodulatory etc, revealing a great potential for calming CS. Therefore, in this timeline review, we report and compare the effects of CCFIAs to attenuate the exacerbation of inflammatory responses by modulating signaling pathways like NF-ĸB, mitogen-activated protein kinase, JAK/STAT, and NLRP3. In addition, we also discuss the role of berberine (BBR) in two different triggers of CS, namely sepsis and viral infections, as well as its clinical applications. These evidence provide a rationale for considering CCFIAs as therapeutic agents against inflammatory CS and this suggestion requires further validation with clinical studies.
ABSTRACT
Background: Previous studies showed that the effect of antivirals for COVID-19 was promising but varied across patient population, and was modest among severe cases. Chinese Medicine (CM) was extensively used and reported effective in China, awaiting further evidence support. We aimed to evaluate the real-world effectiveness of add-on semi-individualized.Methods: A retrospective total sampling cohort of 1788 adult confirmed COVID-19 patients were recruited from all 2235 consecutive records retrieved from 5 hospitals in Wuhan during15 January to 13 March 2020. Consultation notes, laboratory/imaging investigations, pharmacy and prognosis records were linked by an electronic medical record system and verified by at least 2 researchers independently. The mortality of add-on semi-individualized CM users and non-users was compared by weighted hazard ratios of multivariable Cox regression and by propensity score matching. Change of biomarkers was compared between groups and the frequency of CMs used was analysed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. Sensitivity analyses were conducted to test the robustness.Findings: The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a significant mortality reduction of 58% (HR=0.42, 95%CI: 0.23 to 0.77, p=0.005) and 66% (HR=0.34, 95%CI: 0.15 to 0.76, p=0.009) among all and severe/critical COVID-19 cases with dose-dependent response, after inversely weighted with propensity score calculated by age, gender, history of hypertension, diabetes, coronary artery disease and disease severity. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission compared to baseline.Interpretation: Add-on semi-individualized CM was associated with reduced mortality demonstrating dose-dependent response, especially among severe/critical COVID-19 patients. Chinese medicine could be considered as an add-on regimen for trial use.Funding Statement: This work is partially supported by the National Key Research and Development Program (2017YFC1703506 and 2020YFC0841600). Declaration of Interests: No financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the ethics review board of Hubei Provincial Hospital of Traditional Chinese Medicine (HBZY2020-C01-01). Written consent was waived due to the retrospective nature.
Subject(s)
COVID-19 , Diabetes Mellitus , Hypertension , Coronary Artery DiseaseABSTRACT
A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing (Zhejiang Province), a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of two family members living together without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 and offers a glimpse into the early phase of this viral infection outside of Hubei, China.
Subject(s)
COVID-19ABSTRACT
Recently, the coronavirus disease 2019 (COVID-19) has caused a pandemic disease in over 200 countries, influencing billions of humans. To control the infection, identifying and separating the infected people is the most crucial step. The main diagnostic tool is the Reverse Transcription Polymerase Chain Reaction (RT-PCR) test. Still, the sensitivity of the RT-PCR test is not high enough to effectively prevent the pandemic. The chest CT scan test provides a valuable complementary tool to the RT-PCR test, and it can identify the patients in the early-stage with high sensitivity. However, the chest CT scan test is usually time-consuming, requiring about 21.5 minutes per case. This paper develops a novel Joint Classification and Segmentation (JCS) system to perform real-time and explainable COVID-19 chest CT diagnosis. To train our JCS system, we construct a large scale COVID-19 Classification and Segmentation (COVID-CS) dataset, with 144,167 chest CT images of 400 COVID-19 patients and 350 uninfected cases. 3,855 chest CT images of 200 patients are annotated with fine-grained pixel-level labels of opacifications, which are increased attenuation of the lung parenchyma. We also have annotated lesion counts, opacification areas, and locations and thus benefit various diagnosis aspects. Extensive experiments demonstrate that the proposed JCS diagnosis system is very efficient for COVID-19 classification and segmentation. It obtains an average sensitivity of 95.0% and a specificity of 93.0% on the classification test set, and 78.5% Dice score on the segmentation test set of our COVID-CS dataset. The COVID-CS dataset and code are available at https://github.com/yuhuan-wu/JCS.