Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients—implications for treatment

Pettersson, Lisa; Thunberg, Therese; Rocklöv, Joacim; Klingström, Jonas; Evander, Magnus; Ahlm, Clas

doi:10.1111/1469-0691.12259

Cited by 55 publications

(60 citation statements)

References 30 publications

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“…A correlation between high levels of viremia and severity of the disease has been described in previous studies for SNV Virus [Xiao et al, ] and DOBV virus [Saksida et al, ]. A recent report [Pettersson et al, ] asserts that there was a tendency for a higher PUUV RNA load in patients with non‐severe/severe illness during the first 0–3 days. There were no significative differences between non‐severe/ severe cases or between fatal/ non‐fatal cases analyzed in the present study.…”

Section: Discussionmentioning

confidence: 64%

“…Previous studies of viremia in HPS and hemorrhagic fever with renal syndrome (HFRS) suggested an association between initial high viral load of Dobrava (DOBV) [Saksida et al, ], Sin Nombre (SNV) [Terajima et al, ] and Puumala (PUUV) [Pettersson et al, ] viruses, and a severe clinical outcome. Sex‐related differences in susceptibility to virus infection and disease outcome have been proposed but not extensively studied [Martinez et al, ; Klein et al, ; Brundin et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Viral load of patients with hantavirus pulmonary syndrome in Argentina

Bellomo

Pires-Marczeski

Padula

2015

Journal of Medical Virology

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Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Viral load of patients with hantavirus pulmonary syndrome in Argentina

Bellomo

Pires-Marczeski

Padula

2015

Journal of Medical Virology

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“…There are also a number of variables, such as low specific immunoglobulin G titer, that potentially predict severe disease [47] but are not included in this study. Further, the findings show only associations between the different variables in patients with acute PUUV infection.…”

Section: Discussionmentioning

confidence: 99%

Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia

Laine

Koskela

Outinen

et al. 2014

Blood Coagulation &Amp; Fibrinolysis

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Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection.

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“…Although hantaviral disease shows high variability in the intensity and manifestation of symptoms, endothelial dysfunction seems to be the common underlying mechanism of hantavirus infection. Viral replication and im-mune-mediated effects both contribute to tissue damage in hantavirus infection, and the mechanisms of regenerative repair are not known (35)(36)(37)(38)(39)(40)(41)(42). Therefore, we analyzed the role of EPCs in the clinical course of hantavirus infection.…”

mentioning

confidence: 99%

Mobilization of Circulating Endothelial Progenitor Cells Correlates with the Clinical Course of Hantavirus Disease

Krautkrämer

Grouls

Hettwer

et al. 2014

J Virol

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bInfections with hemorrhagic fever viruses are characterized by increased permeability leading to capillary leakage. Hantavirus infection is associated with endothelial dysfunction, and the clinical course is related to the degree of vascular injury. Circulating endothelial progenitor cells (cEPCs) play a pivotal role in the repair of the damaged endothelium. Therefore, we analyzed the number of cEPCs and their mobilizing growth factors in patients suffering from hantavirus disease induced by infection with Puumala virus. The numbers of EPCs of 36 hantavirus-infected patients and age-and gender-matched healthy controls were analyzed by flow cytometry. Concentrations of cEPC-mobilizing growth factors in plasma were determined by enzyme-linked immunosorbent assay. Laboratory parameters were correlated with the number of cEPCs. In patients infected with hantavirus, the number of cEPCs was significantly higher than that in healthy controls. Levels of mobilizing cytokines were upregulated in patients, and the mobilization of cEPCs is paralleled with the normalization of clinical parameters. Moreover, higher levels of cEPCs correlated with higher serum albumin levels and platelet concentrations. Our data indicate that cEPCs may play a role in the repair of hantavirus-induced endothelial damage, thereby influencing the clinical course and the severity of symptoms.

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Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients—implications for treatment

Cited by 55 publications

References 30 publications

Viral load of patients with hantavirus pulmonary syndrome in Argentina

Viral load of patients with hantavirus pulmonary syndrome in Argentina

Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia

Mobilization of Circulating Endothelial Progenitor Cells Correlates with the Clinical Course of Hantavirus Disease

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