Severity Biomarkers in Puumala Hantavirus Infection

Abstract

Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.

Poor Prognosis for Puumala Virus Infections Predicted by Lymphopenia and Dyspnea

“…A recent review summarized severity biomarkers in PUUV orthohantavirus infection ( 12 ). However, almost all mentioned biomarkers are difficult to measure, need special laboratory platforms, or are cost-intensive.…”

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort

“…Consequently, future studies are required to confirm that these identified markers correlate specifically with PUUV-induced thrombocytopenia and AKI, which could play a role in the triage of patients for in- or outpatient treatment. Additionally, it would be of great interest to include other recently discovered blood markers that show the potential of being associated with severe disease, such as complement activation and glycoprotein YKL-40 [ 28 , 29 , 30 ]. Altogether, these findings demonstrate that specific biomarkers of interest in light of PUUV pathogenesis significantly differ between PUUV patients with different disease severity in terms of platelet counts and kidney injury.…”

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome

“…We have detected and evaluated numerous biomarkers in PUUV HFRS (NE), as recently reviewed [ 62 ]. This has been performed with two aims: (i) to understand better the pathogenesis of NE [ 4 ] and (ii) to use the biomarkers to predict the disease severity and long-term consequences of the disease [ 63 , 64 , 65 , 66 ].…”

“…The list of biomarkers evaluated is long: interleukin-6, C-reactive protein (CRP), pentraxin-3, indoleamine 2-3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, resistin, YKL-40, galectin-3 binding protein (Gal-3BP; Mac-2 binding protein), GATA-3, neutrophil gelatinase-associated lipocalin (NGAL), and procalcitonin [ 62 ].…”