Association of iron metabolism with disease severity in acute Puumala hantavirus infection

Serum ferritin is associated with disease severity in haemorrhagic fevers caused by various viruses, while iron has been implicated in the development of acute kidney injury (AKI). Puumala hantavirus causes a haemorrhagic fever with renal syndrome with acute kidney injury (AKI), thrombocytopenia and increased vascular leakage. Histologically acute haemorrhagic tubulointerstitial nephritis is detected. Degrading red blood cells in the kidney are an abundant source of iron and ferritin. Free iron causes oxidative stress. We aimed to evaluate the role of iron metabolism in haemorrhagic fever with renal syndrome caused by Puumala hantavirus. Serum samples from 58 patients in the acute phase and from 51/58 (88%) in the convalescence phase were analysed for variables of iron metabolism and their relationship to the disease severity of acute PUUV infection. During the acute phase, the median concentrations of serum ferritin (1136 vs. 225 µg/L, p < 0.001), hepcidin (386 vs. 51 ng/mL, p < 0.001), and neutrophil gelatinase-associated lipocalin (NGAL) (85 vs. 45 ng/mL, p < 0.001) were elevated, while the median concentrations of serum iron (8.4 vs. 16.2 µmol/L, p < 0.001) and transferrin (1.80 vs. 2.6 g/L, p < 0.001) were reduced compared with the convalescence phase. Serum ferritin, hepcidin, and NGAL levels correlated directly with blood leukocyte count (r = 0.307, p = 0.019; r = 0.318, p = 0.015: r = 0.761, p < 0.001), while the relationship between leukocytes and transferrin was inverse (r=-0.314, p = 0.016). Serum ferritin and hepcidin showed an inverse correlation with the minimum platelet count (r=-0.260, p = 0.048, r=-0.296, p = 0.024, respectively). However, serum ferritin, hepcidin and transferrin did not correlate with serum creatinine or NGAL. Increased serum ferritin and hepcidin levels, as well as decreased transferrin levels, were associated with high leukocyte counts and low platelet counts during acute PUUV infection. However, parameters of iron metabolism were not associated with the severity of AKI in this infection.