托珠单抗在新型冠状病毒肺炎的应用研究探讨

2019年12月以来,新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)在武汉暴发并蔓延至全国,给整个社会带来巨大的挑战。部分COVID-19感染者早期发病并不十分凶险,但后期会突然加速进展,病人很快进入多脏器功能衰竭的状态,李兰娟院士等提出了"细胞因子风暴"概念。但目前并没有特效药物,认为IL-6是诱发细胞因子风暴的重要通路,本文结合相关文献的复习和分析,旨在综述IL-6受体阻断剂托珠单抗在新型冠状病毒肺炎危重患者使用的可行性。     

TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib

COVID-19 emerges as a pandemic disease with high mortality. Development of effective prevention and treatment is an urgent need. We reviewed TH17 responses in patients with SARS-CoV-2 and proposed an FDA approved JAK2 inhibitor Fedratinib for reducing mortality of patients with TH17 type immune profiles.     

中药在抗新型冠状病毒肺炎（COVID-19）引起的细胞因子风暴中的应用分析

2019年12月底新型冠状病毒肺炎(COVID-19)在我国爆发,截止2020年2月23日已感染超7万人,感染者遍布全球28个国家和地区。其传染性强,传播迅速广泛,重症患者可出现急性呼吸窘迫综合征、多器官衰竭等严重并发症。而病毒感染引起的免疫过度激化导致的"细胞因子风暴"是重症患者产生严重并发症的重要原因。目前《新型冠状病毒感染的肺炎诊疗方案》中采用糖皮质激素作为免疫抑制剂,用于遏制重症患者的免疫激化反应,但是糖皮质激素的使用可能会造成二次感染、病程延长等不良预后,且存在严重后遗症风险。而中药在整体免疫调控方面具有明显优势,目前在COVID-19临床治疗中,中西医结合治疗也收到了积极效果。从免疫调控作用入手,分析了单味中药及中药方剂在遏制COVID-19引起的免疫过度激化及细胞因子风暴、抗急性肺损伤的潜在应用价值,有望对现有的诊疗方案中药临床应用做有益补充,发挥抗击疫情的重要作用。     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

Coronavirus and cardiovascular manifestations-getting to the heart of the matter

Coronavirus disease has unarguably been the largest pandemic of recent times. Over 150 million cases have occurred worldwide, and more than 3 million have succumbed to the disease. Cardiac manifestations can have varied presentations from an asymptomatic troponin rise to fulminant myocarditis. The pathogenesis of myocardial damage could be direct or indirect, including inflammation, coronary spasm, plaque rupture, and cytokine storm. Thromboembolism is also an important feature of cardiovascular affliction with both arterial and venous systems being affected. Hence, anticoagulation has also been a matter of debate. Fulminant myocarditis is the most severe form and can lead to circulatory shock with a high mortality. Management of cardiac patients with coronavirus disease 2019(COVID-19) infection is not considerably different from non-COVID-19 cardiovascular disease, but interaction between cardiovascular drugs and antiCOVID-19 therapy requires careful attention. More recently, vaccines have emerged as a ray of hope for the disease. But simultaneously, there have been reports of thromboembolism following vaccination. In this review, we discuss the various aspects of coronavirus disease affecting of heart and its management.     

冠状病毒感染对心血管系统的损伤及可能机制

冠状病毒(coronavirus,CoVs)感染主要累及肺部,但对心血管系统损伤作用也不容忽视。CoVs感染引起的心脏损伤并非罕见,其发生与病情的严重程度密切相关。本文首先从CoVs引起心血管损伤的证据入手,进一步探讨了CoVs对心肌的直接损伤,以及肾素血管紧张素(RAS)系统激活和细胞因子风暴与炎症反应对心血管损伤的可能作用机制。相关心血管损伤的可能机制包括,(1)病毒直接作用:CoVs在心肌细胞复制,损伤心肌;(2)RAS系统激活:感染CoVs后,心脏血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)的表达下调,激活RAS系统,使得血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)收缩血管功能增强,Ang1-7保护心脏效应减弱;(3)诱发细胞因子风暴:循环细胞因子和全身炎症反应引起心脏损伤;(4)其他:包括低氧血症和儿茶酚胺心脏毒性。本文就相关内容作一综述,为后续的详尽机制和治疗策略研究提供思路。     

新型冠状病毒引起的细胞因子风暴及其药物治疗

2019年12月以来,新型冠状病毒(严重急性呼吸综合征冠状病毒2,SARS-CoV-2)感染在武汉暴发。近期不断有专家指出SARS-CoV-2感染者病情的突然加重可能和“炎症风暴”(细胞因子风暴)有关。但目前并无针对于此的特效药。笔者结合相关文献的检索和分析,对细胞因子风暴进行解读,对细胞因子风暴的药物治疗进行探索性综述,以期为临床治疗提供参考。     

COVID-19-induced liver injury in adult patients: A brief overview

Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.