Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still’s Disease: Similarities and Differences

Jianfen Meng,Chengde Yang,Jialin Teng,Xiaobing Cheng,Tingting Liu,Qiongyi Hu,Huihui Chi,Zihan Tang,Xia Chen,Xin Qiao,Yuning Ma,Yue Sun,Zhihong Wang,Hao Zhang,Fan Wang,Mengyan Wang,Hui Shi,Junna Ye,Dehao Zhu,Honglei Liu,Yutong Su,Lei Wan ,Zhongzheng Zhou ,Jieshuang Jia

doi:10.3389/fimmu.2020.603389

Abstract

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still’s disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.

Highlights

Coronavirus disease 2019 (COVID-19), a novel virus-induced acute respiratory disease syndrome, has placed much pressure on healthcare systems with its high mortality rate [1]
Nine articles described the results of IL1b, 31 articles demonstrated the results of IL-6, studies presented the levels of IL-10, reports showed the levels of tumor necrosis factor-a (TNF-a), and only one article depicted data of IL-18
Cytokine storm denotes a hyperactive inflammatory response characterized by systemic inflammation, multi-organ dysfunction, elevated IL-1b, IL-18, IL-6, interferon-g (IFN-g), TNF-a, ferritin, and other mediators, which are injurious to host cells

Summary

Introduction

Coronavirus disease 2019 (COVID-19), a novel virus-induced acute respiratory disease syndrome, has placed much pressure on healthcare systems with its high mortality rate [1]. Increasing evidence suggests that severe COVID-19 patients at higher risk of poor outcomes have higher ferritin levels in serum (1297.6 ng/ml in non-survivors vs 614.0 ng/ml in survivors) [4], leading to a hypothesis that ferritin may act as a bystander of acute phase response and play a pivotal role in inflammation milieu in COVID-19. An inflammatory protein regulated by pro-inflammatory cytokines, may further enhance the pro-inflammatory process in the inflammatory setting of COVID-19, contributing to the development of cytokine storm in COVID-19 [5, 6]. It has spurred comparisons with other severe diseases that are associated with increased cytokines and ferritin

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