1. INTRODUCTION
Severe fever with thrombocytopaenia syndrome virus (SFTSV, officially named Dabie bandavirus ) an emerging tick-borne virus in Asia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and avian influenza A (H5N1) viruses can cause severe and often fatal disease that is characterized by hyperinflammation with features of cytokine storm.[1-5]
The cytokine storm is a common pathogenic characteristic, namely, imbalanced immune responses with an exaggerated inflammatory cytokine reaction, excessive activation of immune cells, and life-threatening systemic inflammatory syndromes, which can cause serious pathological changes and result in multiorgan dysfunction.[1-11]
Interleukin 6 (IL-6) is a proinflammatory cytokine with pivotal roles in inflammation and a key cytokine in cytokine syndrome-induced mortality.[5-11]
IL-10 is a regulatory cytokine with pleiotropic roles in the immune system and is known to be an important immunoregulatory cytokine.[12] However, fatal severe fever with thrombocytopaenia syndrome (SFTS) and severe and critical coronavirus disease 2019 (COVID-19) had significantly higher serum levels of IL-10 than those of patients with mild to moderate and nonfatal illness; in addition, systemic hyperproduction of both IL-6 and IL-10 can generate a cytokine storm, which contributes to their pathology and is more strongly correlated with the outcome of death.[5. 7. 9.10]
Transforming growth factor-β (TGF-β) is a regulatory cytokine with pivotal functions in the control of inflammation. SARS-CoV-2 induces a TGF-β-dominated chronic immune response in severe COVID-19 while TGF‐β was downregulated in SFTS patients compared with healthy controls.[12-15]
In this study, we found that the levels of IL-6 and IL-10 were significantly higher and produced at robust levels in fatal SFTS patients and severe and critically ill COVID-19. In contrast, TGF-β was significantly lower in fatal SFTS and severe and critical COVID-19 patients than in patients with nonfatal SFTS patients and mild to moderate COVID-19. Namely, elevated levels of IL-6 and IL-10 and decreased levels of TGF-β have been linked to severe inflammation and fatality SFTS and in COVID-19 patients.
We also found that IL-10 is elevated earlier than IL-6 and TGF-β, and the blocking of IL-10 signalling using an antibody against the IL-10 receptor can reduce IL-6 production and increase TGF-β production in LPS-induced, SFTSV and SARS-CoV-2 -infected immune cells, respectively, suggesting that IL-10, IL-6 and TGF-β may contribute to disease severity in SFTS COVID-19 and patients.
Therefore, IL-10 plays an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection, and these results demonstrated that targeting IL-10 signalling using a monoclonal antibody against the IL-10 receptor is a potential immune-based intervention against fatal SFTS and severe and critically ill COVID-19 disease.[7, 10]