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      Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors

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          ABSTRACT

          Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group ( n = 17) than in moderate ( n = 42) and severe ( n = 43) group. The levels of IL-10 is positively correlated with CRP amount ( r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

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

          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.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            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.
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              Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

              Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
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                Author and article information

                Journal
                Emerg Microbes Infect
                Emerg Microbes Infect
                Emerging Microbes & Infections
                Taylor & Francis
                2222-1751
                31 May 2020
                2020
                : 9
                : 1
                : 1123-1130
                Affiliations
                [a ]Department of Clinical Laboratory, Renmin Hospital of Wuhan University , Wuhan, People’s Republic of China
                [b ]Department of Clinical Laboratory, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, People’s Republic of China
                [c ]State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University , Wuhan, People’s Republic of China
                [d ]Department of Clinical Laboratory, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, People’s Republic of China
                [e ]Department of Clinical Laboratory, Shanghai Gongli Hospital, the Second Military Medical University , Shanghai, People’s Republic of China
                [f ]Department of Clinical Laboratory, HwaMei Hospital, University of Chinese Academy of Sciences , Ningbo, People’s Republic of China
                [g ]State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, People’s Republic of China
                [h ]Department of Infectious Diseases, Renmin Hospital, Wuhan University , Wuhan, People’s Republic of China
                [i ]Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD, USA
                Author notes
                [CONTACT ] Chengliang Zhu xinchengzhu@ 123456163.com Department of Clinical Laboratory, Renmin Hospital of Wuhan University , Wuhan430060, Hubei, People’s Republic of China
                Yuchen Xia yuchenxia@ 123456whu.edu.cn State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University , Wuhan, People’s Republic of China
                [*]

                These authors have contributed equally to this work.

                Supplemental data for this article can be accessed at https://doi.org/10.1080/22221751.2020.1770129

                Author information
                https://orcid.org/0000-0001-8460-3893
                Article
                1770129
                10.1080/22221751.2020.1770129
                7473317
                32475230
                76e2b247-f5cc-4c2d-88f0-f2a209b276bb
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Figures: 7, Tables: 0, Equations: 0, References: 26, Pages: 8
                Categories
                Research Article
                Articles

                sars-cov-2,covid-19,cytokine storm,inflammatory cytokines,interleukin 6,interleukin 10

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