Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia.
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ABSTRACT:
SUBMITTER: Zhou W
PROVIDER: S-EPMC7035340 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia.
Zhou Wei W Liu Yisi Y Tian Dongdong D Wang Cheng C Wang Sa S Cheng Jing J Hu Ming M Fang Minghao M Gao Yue Y
Signal transduction and targeted therapy 20200221 1
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Project description:The novel coronavirus, 2019-nCoV, has quickly spread across the world and pose serious threat to public health because it can infect people very easily. The major clinical symptoms of 2019-nCoV infection include fever, dry cough, myalgia, fatigue, and diarrhea. The 2019-nCoV belongs to the betacoronavirus family, and gene sequencing results demonstrate that it is a single-stranded RNA virus, closely related to Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). It has been observed that the virus invades human body mainly through binding to angiotensin-converting enzyme 2 (ACE2) receptors similar to SARS-CoV and the main protease (Mpro) acts as a critical protease for digesting the polyprotein into functional polypeptides during the replication and transcription process of 2019-nCoV. In this review, we summarized the real-time information of 2019-nCoV treatment methods and mainly focused on the chemical drugs including lopinavir/ritonavir, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir and other potential innovative active molecules. Their potential targets, activity, clinical status and side effects are described. In addition, Traditional Chinese Medicine (TCM), Convalescent plasma therapy (CPT) and biological reagents available, as well as the promising vaccine candidates against 2019-nCoV are also discussed.
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Project description:2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.
| S-EPMC7162686 | biostudies-literature
Project description:BackgroundA novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients.MethodsWe developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested.ResultsUsing RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10-4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests.ConclusionsThe established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.
| S-EPMC7108203 | biostudies-literature
Project description:At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.
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Project description:BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.MethodsA retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.ResultsTotals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups.ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.
| S-EPMC7908857 | biostudies-literature
Project description:In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
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| S-EPMC7111282 | biostudies-literature
Project description:COVID-19, a novel coronavirus pneumonia (named by the World Health Organization, WHO), has spread widely since the end of 2019. Research on synthetic drugs and vaccines has become a focus of attention in China and other countries, as such approaches are regarded as key tools for disease prevention and control; however, the development of these therapeutics will take months, or even years. Under such circumstances, development of coronavirus specific therapeutics is urgent. For this specific indication, the rapid performance of natural products, such as plant compounds, herbal extracts, and traditional Chinese medicine, could contribute as alternative measures. Recent investigations have provided evidence that these natural products are potential candidates for development as therapeutic agents against the virus that causes COVID-19, 2019-nCoV. Targeting the structural proteins or cellular receptors of 2019-nCoV, including coronavirus chymotrypsin-like (3CLpro or Mpro), helicase (nsP13), S protein, and human angiotensin converting enzyme 2 (ACE2), holds promise for preventing infection. In this review, we summarize some representative natural products and their active components that have potential anti-2019-nCoV effects. We focus on the basic structural elements of 2019-nCoV, its main mechanisms of action, and the feasibility and potential of products to inhibit the novel coronavirus. In addition, the relative advantages, additional functions, and precautions that should be used with typical natural products are also discussed. The aim is to make the case that natural products could be a valuable pool for the development of active compounds for treating 2019-nCoV infection, which may contribute to mitigation of the spread of the pandemic.
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Project description:Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.
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