Coronavirus disease-2019 (COVID-19): Value of IL-6 inhibitors
26 Oct 2020-Vol. 30, Iss: 5, pp 629-644
TL;DR: Despite the effectiveness of inhibiting IL-6 in patients with severe COVID-19, many theoretical and clinical problems of immunopathology and pharmacotherapy of this disease require further study.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has drawn attention to new clinical and fundamental issues in the immunopathology of human diseases. Since in COVID-19 it is the ‘‘hyperimmune’’ response, called cytokine storm syndrome, which forms the basis of the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction in COVID-19, special attention is drawn to the possibility of “repurposing” (drug repurposing) of some widely used for treatment immune-mediated inflammatory rheumatic diseases (IMIRDs) anti-inflammatory drugs, including glucocorticoids (GC), disease-modified anti-rheumatic drugs (DMARDs), biologic agents and ‘‘targeted’’ DMARDs. In the spectrum of cytokines involved in the pathogenesis of cytokine storm syndrome in IMIRDs and COVID-19, great importance is attached to the pro-inflammatory cytokine, interleukin IL-6. The development and introduction into clinical practice of monoclonal antibodies (mAbs) that inhibit the activity of IL-6 are among the major advances in the treatment of IMIRDs, and in recent years, critical conditions within the framework of the cytokine storm syndrome, including in COVID-19. The review discusses the materials of numerous studies devoted to the problems of the efficacy and safety of mAbs to the IL-6 receptor (tocilizumab) and other mAbs that inhibit the activity of this cytokine in COVID-19. Despite the effectiveness of inhibiting IL-6 in patients with severe COVID-19, many theoretical and clinical problems of immunopathology and pharmacotherapy of this disease require further study.
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TL;DR: Patients suffering from chronic noncommunicable diseases need more careful monitoring and preventive measures aimed not only at preventing infection with the new coronavirus, but also at slowing the progression of these pathologies and their complications.
Abstract: An electronic search for publications on the features of the course of COVID-19 in patients with the most common chronic noncommunicable diseases (arterial hypertension, diabetes mellitus and obesity) was carried out using the Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka databases, RSCI, as well as journals peer-reviewed by the Higher Attestation Commission. The review analyzed the effect of comorbidity on the prognosis of a new coronavirus infection (complication rate, severity of the course, mortality). It has been shown that previous noncommunicable diseases are a significant risk factor for adverse outcomes in patients with COVID-19, and if the effect of arterial hypertension is not confirmed by all authors, then type 2 diabetes mellitus, as well as any degree of obesity, are important prognostic signs of an unfavorable course of the new coronavirus infections.
Thus, in the context of the COVID-19 pandemic, patients suffering from chronic noncommunicable diseases need more careful monitoring and preventive measures aimed not only at preventing infection with the new coronavirus, but also at slowing the progression of these pathologies and their complications.
12 Aug 2021
TL;DR: An increase in the level of MRP-8/14 in patients with severe pneumonia associated with influenza A/H1N1 reflects the severity of the course of systemic inflammation and can be considered as a potential point of application of pharmacological action in the intensive care of critical conditions.
Abstract: Background . Today, the critical care medicine is actively developing, and rapid progress is closely related to the achievements of molecular biology, immunology, and pathological physiology. The study of the role of individual molecular structures in the realization of the reactions of innate and adaptive immunity, which underlie the pathogenesis of critical conditions, is an urgent scientific direction and is of interest. Aims. To assess the contribution of the protein complex MRP-8/14 to the development of systemic inflammation by determining its plasma concentration in patients with pneumonia with influenza A/H1N1. Materials and methods . 85 patients with pneumonia associated with influenza A/H1N1 were examined. Of these, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The plasma concentration of the S100A8/A9 protein complex (MRP-8/14) was determined by flow cytometry on an analyzer (Beckman Coulter, USA). Results. It was found that in patients with severe pneumonia with influenza A/H1N1, the concentration of MRP-8/14 increased in 1.9 times compared with healthy. At the same time, in patients with severe pneumonia with influenza A/H1N1 with a fatal outcome, the concentration of MRP-8/14 increased in 2.1 times. Conclusion. An increase in the level of MRP-8/14 in patients with severe pneumonia associated with influenza A/H1N1, on the one hand, reflects the severity of the course of systemic inflammation, on the other hand, the molecules MRP-8 and MRP-14, acting as damage-associated molecular patterns (DAMPs) stimulate a pro-inflammatory response and contribute to the development of critical state. Thereby, the protein complex MRP-8/14 can be considered as a potential point of application of pharmacological action in the intensive care of critical conditions.
References
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Chaolin Huang1, Yeming Wang2, Xingwang Li3, Lili Ren4, Jianping Zhao5, Yi Hu5, Li Zhang1, Guohui Fan2, Jiuyang Xu6, Xiaoying Gu2, Zhenshun Cheng7, Ting Yu1, Jia'an Xia1, Yuan Wei1, Wenjuan Wu1, Xuelei Xie1, Wen Yin5, Li Hui2, Min Liu2, Yan Xiao4, Hong Gao4, Li Guo4, Jungang Xie5, Guang-Fa Wang8, Rongmeng Jiang3, Zhancheng Gao8, Qi Jin4, Jianwei Wang4, Bin Cao2 •
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
Fei Zhou1, Ting Yu, Ronghui Du, Guohui Fan2, Ying Liu, Zhibo Liu1, Jie Xiang3, Yeming Wang4, Bin Song, Xiaoying Gu2, Xiaoying Gu1, Lulu Guan, Yuan Wei, Li Hui1, Xudong Wu, Jiuyang Xu5, Shengjin Tu, Yi Zhang1, Hua Chen, Bin Cao •
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
Nanshan Chen1, Min Zhou2, Xuan Dong1, Jie-Ming Qu2, Fengyun Gong1, Yang Han1, Yang Qiu3, Jingli Wang1, Ying Liu1, Yuan Wei1, Jia'an Xia1, Ting Yu1, Xinxin Zhang2, Li Zhang1 •
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
16,282 citations
Fan Wu1, Su Zhao2, Bin Yu3, Yan-Mei Chen1, Wen Wang3, Zhi gang Song1, Yi Hu2, Zhao Wu Tao2, Jun Hua Tian3, Yuan Yuan Pei1, Ming Li Yuan2, Yu Ling Zhang1, Fa Hui Dai1, Yi Liu1, Qi Min Wang1, Jiao Jiao Zheng1, Lin Xu1, Edward C. Holmes1, Edward C. Holmes4, Yong-Zhen Zhang3, Yong-Zhen Zhang1 •
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
9,231 citations
Additional excerpts
...Пандемия коронавирусной болезни 2019 (COVID-19) [1, 2] привлекла внимание к новым клиническим и фундаментальным проблемам иммунопатологии заболеваний человека....
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TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.
7,493 citations