Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis.

RNA-Seq Revealed a Circular RNA-microRNA-mRNA Regulatory Network in Hantaan Virus Infection

“…Rapidly growing evidence is now mounting that there is a considerable overlap of clinical presentations between HFRS and HPS (Clement et al, 2014). The temporary capillary leak results in sometimes massive interstitial generalized fluid accumulation, leading to different degrees of multiple organ failure (MOF), mainly expressed as acute kidney injury (AKI), and/or as acute lung edema, with or without circulatory shock (Macneil et al, 2011;Jiang et al, 2016;Garanina et al, 2019). However, hantavirus is not a lytic virus.…”

The iatrogenic elevation of neutrophils possibly aggravates lung injury after COVID-19 infection: A case report

“…Among the secondarily symptoms, cytokine storm was identi ed as the inducer, which could be association with excessive activation of immune cells [8]. Based on these, some researchers presumed that excessive immune response promote cytokine storm and further evoke MOF [9,10]. However, so far, the role of neutrophils is not clear in lung injury induced by SARS-CoV-2.…”

“…Secondly, it was considered that the mechanism of organ damage caused by virus infection was related to the inducted immune response. The overactivated leucocytes (monocytes, T lymphocytes, and macrophages) can lead to ARDS and sequential organ failure [9,19]. At present, the detection results from clinical lab showed that SARS-CoV-2 infection usually led to the decrease of leucocytes (including neutrophils, monocytes and lymphocytes) [4].…”

Predictive value of pentraxin-3 on disease severity and prognosis in patients with hemorrhagic fever with renal syndrome

“…After infection with Hantavirus, the human body could develop a strong and rapid immune response characterized by the hyperactivity of immune cells and the ooding of cytokines, so as to the damage of vascular endothelium and visceral organs [1][2][3][4][5][6]. As one of the most important immune cells in innate immunity, neutrophils play a crucial part in resisting bacterial infection.…”