The clinical outcome of Puumala hantavirus (PUUV)
infection shows extensive variation, ranging from inapparent
subclinical infection (70-80%) to severe
hemorrhagic fever with renal syndrome (
HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience
acute kidney injury (AKI), histologically known as acute hemorrhagic
tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the
human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV
infection, and those with B*27 are likely to have a benign
clinical course. Other genetic factors, related to the
tumor necrosis factor (TNF) gene and the C4A component of the
complement system, may be involved. Various autoimmune phenomena and
Epstein-Barr virus infection are associated with PUUV
infection, but hantavirus-
neutralizing antibodies are not associated with lower disease severity in PUUV
HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of
nephropathia epidemica (NE). Numerous
biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV
infection. A new addition is the plasma
glucose concentration associated with the severity of both capillary leakage,
thrombocytopenia,
inflammation, and AKI in PUUV
infection. Our question, "Why this variation?" remains largely unanswered.