Serological tests for COVID-19: Potential opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus, caused a pandemic leading to a standstill of nearly all global activities. There are some controversies on the production of specific immunoglobulin M (IgM) and IgG antibodies after the infection with SARS-CoV-2. This paper seeks to elaborate on the potential application of IgM and IgG antibodies and the viral antigens for the diagnosis and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge.     

抗病毒肽作为COVID-19潜在治疗药物的研究进展

随着新型冠状病毒(SARS-CoV-2)疫情的迅速蔓延,目前该疾病已发展成为世界范围流行病。世界卫生组织WHO在2020年2月11日将该疾病正式命名为Coronavirus disease(COVID-19)。新型冠状病毒肺炎严重威胁着人们的生命财产安全,安全高效抗病毒类药物的开发是目前亟需解决的重要问题。研究报道,很多抗病毒肽(Antiviral peptides,AVPs)显示出良好的抗病毒活性,结合当前临床抗新冠病毒乏力的情况,本文对冠状病毒感染过程以及抗病毒肽的潜在应用前景进行概述,以期为开发新型抗病毒药物提供新的思路。     

Lymphopenia in COVID‐19: Therapeutic opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS‐CoV‐2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.     

Therapeutic options of TCM for organ injuries associated with COVID-19 and the underlying mechanism

BackgroundCoronavirus disease-2019 (COVID-19) caused by infection with severe acute respiratory coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout China and in other countries since the end of 2019. The World Health Organization (WHO) has declared that the epidemic is a public health emergency of international concerns. The timely and appropriate measures for treating COVID-19 in China, which are inseparable from the contribution of traditional Chinese medicine (TCM), have won much praise of the world.PurposeThis review aimed to summarize and discuss the essential role of TCM in protecting tissues from injuries associated with COVID-19, and accordingly to clarify the possible action mechanisms of TCM from the perspectives of anti-inflammatory, antioxidant and anti-apoptotic effects.MethodsElectronic databases such as Pubmed, ResearchGate, Science Direct, Web of Science, medRixv and Wiley were used to search scientific literatures.ResultsThe present review found that traditional Chinese herbs commonly used for the clinical treatment of organ damages caused by COVID-19, such as Scutellaria baicalensis, Salvia miltiorrhizaSalvia miltiorrhiza, and ginseng, could act on multiple signaling pathways involved in inflammation, oxidative stress and apoptosis.ConclusionTCM could protect COVID-19 patients from tissue injuries, a protection that might be, at least partially, attributed to the anti-inflammatory, antioxidant and anti-apoptotic effects of the TCM under investigation. This review provides evidence and support for clinical treatment and novel drug research using TCM.     

Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients

SARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Previous studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited.We addressed the gap of existing knowledge with regard to a differentiated understanding of disease dynamics in SARS-CoV-2 infection while specifically considering disease stage and severity. We biomedically characterized quantitative proteomics in a hospitalized cohort of COVID-19 patients with mild to severe symptoms suffering from different (co)-morbidities in comparison to both healthy individuals and patients with non-COVID related inflammation. Deep clinical phenotyping enabled the identification of individual disease trajectories in COVID-19 patients.By the use of the individualized disease phase assignment, proteome analysis revealed a severity dependent general type-2-centered host response side-by-side with a disease specific antiviral immune reaction in early disease. The identification of phenomena such as neutrophil extracellular trap (NET) formation and a pro-coagulatory response characterizing severe disease was successfully validated in a second cohort. Together with the regulation of proteins related to SARS-CoV-2-specific symptoms identified by proteome screening, we not only confirmed results from previous studies but provide novel information for biomarker and therapy development.     

Strategies for antiviral resistance in transgenic plants

Genetic engineering offers a means of incorporating new virus resistance traits into existing desirable plant cultivars. The initial attempts to create transgenes conferring virus resistance were based on the pathogen-derived resistance concept. The expression of the viral coat protein gene in transgenic plants was shown to induce protective effects similar to classical cross protection, and was therefore distinguished as 'coat-protein-mediated' protection. Since then, a large variety of viral sequences encoding structural and non-structural proteins were shown to confer resistance. Subsequently, non-coding viral RNA was shown to be a potential trigger for virus resistance in transgenic plants, which led to the discovery of a novel innate resistance in plants, RNA silencing. Apart from the majority of pathogen-derived resistance strategies, alternative strategies involving virus-specific antibodies have been successfully applied. In a separate section, efforts to combat viroids in transgenic plants are highlighted. In a final summarizing section, the potential risks involved in the introduction of transgenic crops and the specifics of the approaches used will be discussed.     

Clinical trials with antiviral drugs against COVID-19: some progress and many shattered hopes

Vaccines and drugs are the cornerstones in the fight against the SARS-CoV-2 pandemic. While vaccines were a success story, the development of antiviral drugs against SARS-CoV-2 turned out to be difficult. For an accelerated use of antivirals in the clinic, most SARS-CoV-2 antivirals represented repurposed drugs. The present article summarizes the outcomes of clinical trials with antiviral drugs in COVID-19 patients. Many antiviral drugs failed to demonstrate beneficial effects or showed mixed results. One reason for the low success rate of clinical trials was shortcomings of antiviral tests in cell culture systems and another reason was the abundance of ill-coordinated and underpowered clinical trials. However, large pragmatic clinical trials particularly of the British RECOVERY trial series demonstrated that even under emergency situation drug trials can be conducted in a timely way such that the therapy of COVID-19 patients can be based on evidence basis instead on expert opinion or even worse on political pressure.     

Therapeutic opportunities in polyglutamine disease

Polyglutamine diseases comprise a class of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine tracts. Great progress has been made in elucidating the molecular mechanisms contributing to polyglutamine pathology, and in identifying potential drug targets. Although much remains to be learned, these advances provide an opportunity for rational approaches to target-based drug discovery.     

Gut microbiota in antiviral strategy from bats to humans:a missing link in COVID-19

Bats are a potential natural reservoir for SARS-CoV-2 virus and other viruses detrimental to humans. Accumulated evidence has shown that, in their adaptation to a flight-based lifestyle, remodeling of the gut microbiota in bats may have contributed to immune tolerance to viruses. This evidence from bats provides profound insights into the potential influence of gut microbiota in COVID-19 disease in humans. Here, we highlight recent advances in our understanding of the mechanisms by which the gut microbiota helps bats tolerate deadly viruses, and summarize the current clinical evidence on the influence of gut microbiota on the susceptibility to SARS-CoV-2 infection and risk of COVID-19 leading to a fatal outcome. In addition, we discuss the implications of gut microbiota-targeted approaches for preventing infection and reducing disease severity in COVID-19 patients.     

新型冠状病毒疫苗研究策略分析

新型冠状病毒(SARS-CoV-2)是一种可引起人新型冠状病毒肺炎(COVID-19)的新发呼吸道病原体,与重症急性呼吸道综合症冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)同属于β-冠状病毒,具有较高的传染性和一定的致死率。2019年12月在我国武汉被发现,随后蔓延到我国大部分省份,给我国人民健康和经济发展造成巨大损失。疫苗接种是预防和控制传染病的常规和有效手段,国内外多个机构已启动COVID-19疫苗研究工作。文中基于SARS和MERS疫苗研究的经验和教训,对COVID-19疫苗的研究策略和需要注意的关键问题进行了阐述,为相关研究人员提供参考。     

Immunology of COVID-19

The immune response to SARS-CoV-2 reveals a delicate balance between protective effects and harmful pathological reactions and can possibly explain the highly variable disease manifestations in subjects infected with this novel coronavirus. A better understanding of the anti-viral immune response is not only critical for vaccine development but might also provide targets for pharmaceutical and immunological treatment options. Recent research literature on immune aspects of COVID-19 is summarized in this review with an outlook how bats have evolved to live with these viral infections.