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      Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

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          Abstract

          The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.

          Highlights

          • •

            Cytokine release syndrome (CRS) contributes to life-threatening multiple organ dysfunction in coronavirus disease 2019 (COVID-19) and represents a potential therapeutic target.

          • •

            Mechanistic understanding of CRS permits the design of novel immunotherapies.

          • •

            Targeting key molecules within the inflammatory cytokine network, such as interleukin-6 (IL-6), is a novel strategy for COVID-19-induced CRS and warrants further investigation.

          • •

            Abstract.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
          Article 0 comments Cited 21890 times – based on 0 reviews     Review now
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
            Article 0 comments Cited 10817 times – based on 0 reviews     Review now
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              Is Open Access

              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
              Article 0 comments Cited 10138 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xuan Guan
                Yufei Xiang
                Journal
                Journal ID (nlm-ta): J Autoimmun
                Journal ID (iso-abbrev): J. Autoimmun
                Title: Journal of Autoimmunity
                Publisher: Elsevier Ltd.
                ISSN (Print): 0896-8411
                ISSN (Electronic): 1095-9157
                Publication date PMC-release: 10 April 2020
                Publication date (Electronic): 10 April 2020
                Electronic Location Identifier: 102452
                Affiliations
                [a ]Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
                [b ]Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
                [c ]Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
                [d ]Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China
                [e ]Department of Internal Medicine, AdventHealth Orlando, Orlando, USA
                Author notes
                [∗ ]Corresponding author. Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. yufei.xiang@ 123456csu.edu.cn
                [∗∗ ]Corresponding author. xuan.guan.md@ 123456adventhealth.com
                Article
                Publisher ID: S0896-8411(20)30067-6 Publisher ID: 102452
                DOI: 10.1016/j.jaut.2020.102452
                PMC ID: 7151347
                PubMed ID: 32291137
                SO-VID: 2ebec25e-a84b-4efb-9b6c-d0a523235741
                Copyright © © 2020 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 3 March 2020
                Date revision received : 29 March 2020
                Date accepted : 2 April 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Immunology
                Keywords: coronavirus disease 2019,cytokine release syndrome,interleukin-6,tocilizumab,manuscript
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: coronavirus disease 2019, cytokine release syndrome, interleukin-6, tocilizumab, manuscript

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