A patient with severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis-associated involvement of the central nervous system

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

“…Systemic dissemination of SFTSV-infected B cells in fatal SFTS. SFTSV-infected cells have been detected in multiple nonlymphoid organs, such as the liver, adrenal glands, intestine, heart, lungs, and kidneys in most examinations of fatal human SFTS (18,34,37). Here, we analyzed, by IHC, the distribution of SFTSVinfected cells in nonlymphoid organs obtained postmortem from 22 individuals with fatal SFTS.…”

“…Despite the high awareness within the medical community in SFTS-endemic areas, and the use of antiviral therapy such as ribavirin, the case fatality rate of SFTS is still as high as 15%, which is the same as other severe viral diseases including viral hemorrhagic fevers (15). In SFTS, inflammatory cytokine storms (11,(16)(17)(18)(19) as well as impairment of immune responses including innate immunity (14,(20)(21)(22)(23)(24)(25), antiviral T cell function (26), and antiviral humoral responses (27) have important roles in the pathogenic progress of lethal infections. Immune impairment and high viral loads are also characteristics of several other viral hemorrhagic fevers (28), but these diseases differ in terms of pathology and pathogenesis, about which little is known for SFTS.…”

“…Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections in lymphoid organs such as the lymph nodes, spleen, and bone marrow (6,18,34). However, reported numbers of infected cells in these organs vary considerably.…”

“…In addition, elucidation of the cell and tissue tropism associated with mortality can explain viral lethality (33). Results from histopathological studies have shown that necrotizing lymphadenitis and prominent hemophagocytosis are the pathological characteristics of fatal SFTS, and large atypical immunoblastic cells are major infected cells in the lymph nodes, spleen, and bone marrow (6,18,(34)(35)(36)(37). However, detailed characterization of the viral target cells and tissues is required to understand the pathogenic mechanisms of lethal SFTSV infection.…”

Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy

“…It was thought that the deterioration of consciousness and other CNS-associated symptoms that appeared in the severely ill SFTS patients were a result of indirect effects induced by HLH associated with cytokine storm. However, the findings that pathological changes appeared in the CNS, into which SFTSV antigen-positive cells infiltrated, suggests that there might be cases of SFTS in which deterioration of CNS function is due directly to the SFTSV infection [24].…”