Differential Cytokine Responses and the Clinical Severity of Adult and Pediatric Nephropathia Epidemica

Abstract

Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed in children. This limited number of pediatric NE cases means there is an inadequate understanding of disease pathogenesis in this age category. Here, we have analyzed clinical and laboratory data in adults and children with NE to establish whether and how the disease severity differs between the two age groups. Serum cytokines were analyzed in samples collected from 11 children and 129 adult NE patients during an outbreak in 2019. A kidney toxicity panel was also used to analyze urine samples from these patients. Additionally, serum and urine samples were analyzed from 11 control children and 26 control adults. Analysis of clinical and laboratory data revealed that NE was milder in children than in adults. A variation in serum cytokine activation could explain the differences in clinical presentation. Cytokines associated with activation of Th1 lymphocytes were prominent in adults, while they were obscured in sera from pediatric NE patients. In addition, a prolonged activation of kidney injury markers was found in adults with NE, whilst only a short-lasting activation of these markers was observed in children with NE. These findings support previous observations of age differences in NE severity, which should be considered when diagnosing the disease in children.

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

“…Hantavirus infection induces a cytokine storm activating a plethora of immunopathological processes. Age‐ and gender‐dependent differences were described in the immune response against hantavirus infection 10–12 . Several cytokines and markers of cellular damage have been identified to be associated with severity of clinical course in hantavirus infection 7,13–23 …”

“…Age-and gender-dependent differences were described in the immune response against hantavirus infection. [10][11][12] Several cytokines and markers of cellular damage have been identified to be associated with severity of clinical course in hantavirus infection. 7,[13][14][15][16][17][18][19][20][21][22][23] The balanced host immune reaction determines the severity of disease by eradication of the invading pathogen but avoiding detrimental tissue damage due to poorly controlled immune activation.…”