IL-15 immunotherapy is a viable strategy for COVID-19

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8⁺ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19.     

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。     

A Study of Two Cases Co-Infected with SARS-CoV-2 and Human Immunodeficiency Virus

Since December 2019, A new type of coronavirus pneumonia (coronavirus disease 2019, COVID-19) has become endemic in Wuhan, China. So far, COVID-19 has developed into a global epidemic. The body's immune system plays an important role in the fight against COVID-19. Here, we followed up the clinical data and treatment of two COVID-19 patients diagnosed with acquired immunodeficiency syndrome (AIDS), hoping to be helpful for the subsequent diagnosis and treatment of patients with related diseases.     

新型冠状病毒SARS-CoV-2研究进展

在武汉发生的由新型冠状病毒SARS-CoV-2引发的人类冠状病毒病COVID-19,仅仅2个多月时间在我国及国际上70多个国家出现迅速传播,致病和死亡率高,人类生命受到了极大威胁。一些科学家火速投入研究,对SARS-CoV-2的来源和进化、形态特征和基因结构、感染和致病分子机制开展深入研究,取得了重大进展,为科学防控COVID-19提供了重要依据。根据上述研究的基础,文中对COVID-19病毒疫苗、抗体和抑制剂研发提出了设想,在研究防控COVID-19核心技术上具有一定的参考价值。     

Potential natural candidates in the treatment of coronavirus infections

Many viral infections do not have treatments or resistant to existing antiviral therapeutic interventions, and a novel strategy is required to combat virus-mediated fatalities. A novel coronavirus (coronavirus disease 2019 [COVID-19]) emerged in Wuhan, China, in late 2019 and rapidly spread across the globe. COVID-19 has impacted human society with life-threatening and unprecedented health, social, and economic issues, and it continues to affect millions of people. More than 5,800 clinical trials are in place worldwide to develop treatments to eradicate COVID-19. Historically, traditional medicine or natural products, such as medicinal plants, marine organisms and microbes, have been efficacious in treating viral infections. Nevertheless, important parameters for natural products, including clinical trial information, pharmacokinetic data, potency and toxicity profiles, in vivo and in vitro data, and product safety require validation. In this review article, an evaluation is performed of the potential application of natural product-based antiviral compounds, including crude extracts and bioactive chemical compounds obtained from medicinal plants, marine organisms, and microbes, to treat the viral infections COVID-19.     

Long-term predictions of current confirmed and dead cases of COVID-19 in China by the non-autonomous delayed epidemic models

In this paper, we make long-term predictions based on numbers of current confirmed cases, accumulative dead cases of COVID-19 in different regions in China by modeling approach. Firstly, we use the SIRD epidemic model (S-Susceptible, I-Infected, R-Recovered, D-Dead) which is a non-autonomous dynamic system with incubation time delay to study the evolution of the COVID-19 in Wuhan City, Hubei Province and China Mainland. According to the data in the early stage issued by the National Health Commission of China, we can accurately estimate the parameters of the model, and then accurately predict the evolution of the COVID-19 there. From the analysis of the issued data, we find that the cure rates in Wuhan City, Hubei Province and China Mainland are the approximately linear increasing functions of time t and their death rates are the piecewisely decreasing functions. These can be estimated by finite difference method. Secondly, we use the delayed SIRD epidemic model to study the evolution of the COVID-19 in the Hubei Province outside Wuhan City. We find that its cure rate is an approximately linear increasing function and its death rate is nearly a constant. Thirdly, we use the delayed SIR epidemic model (S-Susceptible, I-Infected, R-Removed) to predict those of Beijing, Shanghai, Zhejiang and Anhui Provinces. We find that their cure rates are the approximately linear increasing functions and their death rates are the small constants. The results indicate that it is possible to make accurate long-term predictions for numbers of current confirmed, accumulative dead cases of COVID-19 by modeling. In this paper the results indicate we can accurately obtain and predict the turning points, the end time and the maximum numbers of the current infected and dead cases of the COVID-19 in China. In spite of our simple method and small data, it is rather effective in the long-term prediction of the COVID-19.     

Are we fully exploiting type I Interferons in today's fight against COVID-19 pandemic?

Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) – mainly IFN-α and β –represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.     

The COVID-19 pandemic and physical activity during intermittent fasting,is it safe? A call for action

Intermittent fasting (IF) has recently gained popularity, and has been used for centuries in many religious practices. The Ramadan fasting is a mandatory form of IF practiced by millions of healthy adult Muslims globally for a whole lunar month every year. In Islam, the “Sunna” also encourages Muslims to practice IF all along the year (e.g.; two days a week). The 2019-Coronavirus disease (COVID-19) pandemic in the context of Ramadan has raised the question whether fasting is safe practice during the COVID-19 pandemic health crisis, and what would be the healthy lifestyle behaviors while fasting that would minimize the risk of infection. As COVID-19 lacks a specific therapy, IF and physical activity could help promote human immunity and be part of holistic preventive strategy against COVID-19. In this commentary, the authors focus on this dilemma and provide recommendations to the fasting communities for safely practicing physical activity in time of COVID-19 pandemic.     

From impossible to possible: the lessons from the control of recent COVID-19 outbreaks in China

The COVID-19 pandemic has catastrophically impacted the world. Before the success in vaccination, this virus shows no sign of stop spreading. Nearly all the countries have implemented stringent approaches to slow down the transmission of the virus, but the virus still caused over 2 million deaths and the number is increasing. Therefore, preventing the virus spreading is still necessary to protect most people, especially the ones with pre-conditions. Mainland China has successfully eradicated the COVID-19 virus infection in Wuhan in 2020. After that, several small-scale outbreaks occurred in many cities in China, but none of these COVID-19 virus infections caused the widespread. In this review, we would like to give a detailed presentation of the approaches that were implemented by the China government to suppress the virus spreading by considering the unique characteristics of this virus and the paths of the virus transmission. Both the pros and cons of these strategies will also be analyzed. The experiences and lessons learned during the virus-fighting in China, expectedly, will be a useful source of reference for other regions in overcoming the threat caused by the COVID-19 virus.     

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics

An epidemic caused by COVID-19 in China turned into pandemic within a short duration affecting countries worldwide. Researchers and companies around the world are working on all the possible strategies to develop a curative or preventive strategy for the same, which includes vaccine development, drug repurposing, plasma therapy, and drug discovery based on Artificial intelligence. Therapeutic approaches based on Computational biology and Machine-learning algorithms are specially considered, with a view that these could provide a fast and accurate outcome in the present scenario. As an effort towards developing possible therapeutics for COVID-19, we have used machine-learning algorithms for the generation of alignment kernels from diverse viral sequences of Covid-19 reported from India, China, Italy and USA. Using these diverse sequences we have identified the conserved motifs and subsequently a peptide library was designed against them. Of these, 4 peptides have shown strong binding affinity against the main protease of SARS-CoV-2 (M^pro) and also maintained their stability and specificity under physiological conditions as observed through MD Simulations. Our data suggest that these evolutionary peptides against COVID-19 if found effective may provide cross-protection against diverse Covid-19 variants.     

Focus: Preventive Medicine: The Impact of the Social Distancing Policy on COVID-19 Incidence Cases and Deaths in Iran from February 2020 to January 2021: Insights from an Interrupted Time Series Analysis

Background: In December 2019, a viral outbreak occurred in China, and rapidly spread out worldwide. Due to the lack of immediately available vaccines and effective drugs, many policy- and decision-makers have focused on non-pharmacological methods, including social distancing. This study was aimed at assessing the effects of the implementation of this policy in Iran, one of the countries most affected by COVID-19. We conducted a quasi-experimental study, utilizing the interrupted time series analysis (ITSA) approach. Methods: We collected daily data between February 20, 2020 and January 29, 2021, through governmental websites from 954 public hospitals and healthcare settings. The Iranian government launched the social distancing policy on March 27, 2020. Statistical analyses, including ITSA, were carried out with R software Version 3.6.1 (London, UK). Results: During the study period, 1,398,835 confirmed incidence cases and 57,734 deaths occurred. We found a decrease of -179.93 (95% CI: -380.11 to -20.25, P-value=0.078) confirmed incidence cases following the implementation of the social distancing policy, corresponding to a daily decrease in the trend of -31.17 (95% CI: -46.95 to -15.40, P-value=0.08). Moreover, we found a decrease of -28.28 (95% CI: -43.55 to -13.01, P-value=0.05) deaths, corresponding to a daily decrease in the trend of -4.52 (95% CI: -5.25 to -3.78, P-value=0.003). Conclusion: The growth rate of confirmed incidence cases and deaths from COVID-19 in Iran has decreased from March 27, 2020 to January 29, 2021, after the implementation of social distancing. By implementing this policy in all countries, the burden of COVID-19 may be mitigated.     

Assessing the effectiveness of mandatory outdoor mask policy: The natural experiment of Campania

Face masks are possibly the main symbol of the COVID-19 pandemic. Once rarely used in Western countries, in the last two years they have become an object it is impossible to leave one’s home without. Italy made their use a legal requirement, even outdoors, from late 2020 to early 2022. The effectiveness of this policy in reducing COVID-19 cases has been widely debated. The recent cancellation of their mandatory use in Italy offers an interesting setting in which to test its impact, since one Italian region (Campania) extended the restriction for a further three weeks. We aim to shed some light on the real-world impact of mandatory use of face masks outdoors, identifying the effect of this policy on the spread of COVID-19. By means of a quantitative analysis, employing a synthetic control method approach, we find that Campania had statistically the same number of cases as its synthetic counterfactual, built from a donor pool formed from the other Italian provinces. Hence, results suggest that while it imposes a burden on the public, the use of face masks outdoors is not correlated with a decrease in the number of COVID-19 cases.     

Assessment of risk management and control measures against coronavirus disease

This article presents the COVID-19 situation and control measures taken by the Government of Pakistan. Two waves of pandemic are faced globally and similar in the study area. We have investigated the risk management decision in two phases. Primarily, strict lockdown was observed from March 2020 to July 2020 and smart lockdown was enforced from August 2020 to December 2020. It has been studied that during strict lockdown, COVID cases reduced gradually but reopening of institutes and smart lockdown strategy resulted gradual increase in confirmed cases and death rates. During first wave of COVID-19 in Pakistan, a total confirmed number of patients of COVID-19 were 263,496 till 18th of July 2020 with total deaths of 5,568 people and 204,276 recoveries, while total number of COVID-19 patients reached 555,511 till 9th of February 2021 with total deaths of 12,026 people. Province of Sindh was affected badly with total number of 251,434 COVID-19 cases followed by Punjab Province with total number of 161,347 COVID-19 till 9th of February 2020.     

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.     

中草药在防治新型冠状病毒肺炎中的应用

新型冠状病毒肺炎(COVID-19)是由新型冠状病毒引起的突发性传染病,具有极强的传染性和致病性,感染者常伴有发烧、乏力、咳嗽等症状,自2019年12月首次发现以来,新型冠状病毒肺炎迅速席卷全球,受到国内外高度关注。中医药是我国传统特色文化,国家卫健委、中医药管理局在《新型冠状病毒感染的肺炎诊疗方案(试行第三版)》中首次推出中医药治疗方案,其中清热解毒、补气活血、清肺化痰等中药为新冠肺炎防治中常用中草药类型,槲皮素、山奈酚、黄芩素等黄酮类成分为主要活性成分。实践证明,中草药在抗病毒、抗炎、减轻患者症状等方面有显著效果,特别是我国新冠肺炎患者总体治愈率达94%以上,远高于其他国家。文中在概述新型冠状病毒特征的基础上,综述中医药治疗新冠肺炎中涉及的药用植物及其有效成分研究进展,为防治新冠肺炎药物研发提供参考。     

Contribution of traditional Chinese medicine to the treatment of COVID-19

COVID-19 as an epidemic disease has spread across the planet since December 2019. The somber situation reminds each country to take actions in preventing the spreading of the virus. China as one of the early affected countries has been fighting against the novel coronavirus with the achievements of nearly 80,000 cured confirmed patients. Traditional Chinese medicine (TCM) has made contributions to the treatment of COVID-19 because of its efficacy and comprehensive therapeutic theory. In this commentary, the advantage, etiology and mechanism of TCM therapy were discussed in the aspect of its functions in reducing the harms brought by COVID-19 to human beings.     

新型冠状病毒与系统损伤研究

自2019年12月全国及世界范围爆发了新型冠状病毒性肺炎(corona virus disease 2019,COVID-19),给中国和全球公共卫生安全带来了极大的挑战.研究发现,新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)不仅损...     

战“疫”时期“病毒生物学”课程的教学调整与思考

2020年春天,全球进入对抗新型冠状病毒(Severe Acute Respiratory Syndrome Coronavirus 2,SARS-CoV-2)感染引起的"新冠"肺炎(Coronavirus Disease,COVID-19)疫情的斗争中。为了适应全民抗"疫"的新形势,引导学生理性地、科学地认识此次病毒疫情,"病毒生物学"课程的教学从内容到形式也进行了同步设计与微调。除了将教学模式由线下教学变成线上直播,本课程结合疫情发展情况在学期初进行COVID-19的专题讲座,以及通过"COVID-19-5 min"形式每次上课进行疫情周报解读,分析国内外疫情并传授病毒流行病学相关知识。另外,对"病毒生物学"的教学计划和教学内容做了适当微调,更多关注病毒性传染疾病发展和相关科学研究的进展。通过对在线教学从教学模式、教学过程和教学内容的设计和调整,强化教学效果的反馈和改善,引导学生不信谣、不传谣,帮助学生加强对新型冠状病毒(SARS-CoV-2)及疫情的科学认识。通过教学内容和教学形式的调整以及病毒疫情相关知识点的强化,激发了生物学专业学生对病毒学、流行病学及公共卫生健康等问题的关注。     

Lipidomic alteration of plasma in cured COVID-19 patients using ultra high-performance liquid chromatography with high-resolution mass spectrometry

Background: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood.Methods: In the present study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison.Results: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters (ChE). Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways.Conclusions: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to undergo consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.     

中国和伊朗新型冠状病毒肺炎流行现状及比较分析

新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)已造成全球大流行,比较不同国家流行特征是了解该病流行规律的重要内容。为了推进我国提出的"一带一路"倡议,防止传染病跨境传播,并探讨COVID-19流行规律和不同国家传染病研究方法,本研究对中国和伊朗COVID-19流行特征和影响因素进行比较分析。根据世界卫生组织、国家卫生健康委员会及新闻媒体等提供的数据和信息,采用描述流行病学方法和Pearson相关进行分析,结果显示,截至2020年7月31日24时,中国累计报告确诊病例88122例,占全球报告0.50%,位居28位;同期伊朗确诊304204例,占全球1.73%,位居全球第9位。2020年4月22日伊朗报告累计确诊病例数首次超过中国,中国宁夏回族自治区、北京市、上海市、甘肃省、广东省分别报告有伊朗输入病例。COVID-19流行水平和严重程度伊朗高于中国:伊朗的发病率为371/10万、中国6.29/10万;伊朗的死亡率为20/10万、中国0.33/10万;伊朗的治愈率为86.63%、中国为92.18%;病死率两国水平接近;伊朗平均每日新增确诊病例数1395例,中国404例。中国疫情出现拐点的时间较伊朗早,每日新增确诊病例首次出现下降用时25d(伊朗42d)、每日新增治愈超过新增确诊用时31d(伊朗49d)。伊朗疫情在5月后出现持续反弹,2020年6月4日确诊病例数达反弹峰值(3574例),超过前期的3186例,且在多数时间新增治愈人数低于新增确诊人数。中国和伊朗每日新增确诊、新增治愈病例数趋势形态不同,中国新增治愈病例数趋势图整体延后新增确诊病例,而伊朗新增治愈与新增确诊病例数几乎同步。相关分析显示武汉每日新增确诊病例数在划分的两个阶段与预防控制措施得分均呈正相关(相关系数分别为0.44、0.53),而与当时武汉的气象因素平均气压(百帕)、平均2min风速(米/秒)、平均气温(℃)、平均相对湿度(百分率)、日照时数(时)无相关性;伊朗在疫情的第一阶段呈正相关,第二阶段为负相关。COVID-19在中国和伊朗的流行存在差异,对不同国家流行情况进行比较研究,有助于加深对COVID-19全球大流行的认识。