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Cardiopulmonary involvement in Puumala hantavirus infection
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
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2013 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 13, no 1, 501- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Hantavirus infections cause potentially life-threatening disease in humans world-wide. Infections with American hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. Pulmonary involvement in European Puumala hantavirus (PUUV) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. We aimed to comprehensively investigate cardiopulmonary involvement in patients with PUUV-infection.

METHODS: Twenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data.

RESULTS: Two-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered.

CONCLUSIONS: In a majority of patients with PUUV-infection, both cardiac and pulmonary involvement was demonstrated with implications on patients' recovery. The results demonstrate vascular leakage in the lungs that most likely is responsible for impaired gas diffusing capacity and increased pulmonary vascular resistance with secondary pulmonary hypertension and right heart distress. Interestingly, NT-ProBNP was markedly elevated even in the absence of overt ventricular heart failure. The method of simultaneous investigations of important cardiac and respiratory measurements improves the interpretation of the underlying pathophysiologic mechanisms.

Place, publisher, year, edition, pages
BioMed Central, 2013. Vol. 13, no 1, 501- p.
National Category
Infectious Medicine
URN: urn:nbn:se:umu:diva-83698DOI: 10.1186/1471-2334-13-501ISI: 000328902800001PubMedID: 24160911OAI: diva2:675791
Available from: 2013-12-04 Created: 2013-12-04 Last updated: 2016-05-24Bibliographically approved
In thesis
1. Cardiopulmonary involvement in Puumala hantavirus infection
Open this publication in new window or tab >>Cardiopulmonary involvement in Puumala hantavirus infection
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in Europe. After inhalation of virus shed by bank voles, the virus systemically targets the vascular endothelium leading to vascular dysfunction and leakage. Many patients with PUUV infection experience cardiopulmonary manifestations but the underlying mechanisms have not been determined.

The aims of the studies presented were to describe cardiopulmonary manifestations, investigate pathogenetic mechanisms including presence of virus in the lungs and the local immune response in PUUV infection.

The results showed cardiopulmonary involvement of varying severity in almost all studied patients. High-resolution computed tomography frequently revealed vascular leakage into the lungs or pleural cavities. Pulmonary function tests generally showed reduced gas diffusing capacity, evidenced in patients as dyspnea, poor oxygenation and frequent need of oxygen treatment. Among patients who were not fully recovered at 3 months follow-up, remaining decreased gas diffusing capacity was highly common.

Echocardiography revealed mainly right heart dysfunction which was related to manifestations within the lungs, in terms of increased estimated pulmonary vascular resistance, mild to moderate pulmonary hypertension, and reduced right ventricular systolic function in patients with more pronounced lung involvement, as indicated by need of oxygen treatment.

Analyses on bronchoalveolar lavage (BAL) and bronchial biopsies revealed a highly activated cytotoxic T cell (CTL) response in the lungs. The CTL response was not balanced by the expansion of regulatory T cells and high numbers of CTLs were associated with more severe disease. PUUV RNA was detected in almost all patients’ BAL samples and the viral load was inversely correlated to the number of CTLs.

Three patients presenting with severe and fatal cardiopulmonary distress were also described. Autopsies revealed PUUV protein in vascular endothelium in all investigated organs, including the heart and lungs, along with a massive CTL response mainly in the lungs.

In conclusion, cardiopulmonary involvement of varying severity was present in almost all patients with PUUV infection. Cytotoxic immune responses could contribute to disease development but also help in clearing the infection. Long lasting fatigue after hantavirus infection may be explained by remaining manifestations within the lungs. 

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2015. 69 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1698
Hemorrhagic fever with renal syndrome, hantavirus, echocardiography, respiratory function tests, computed tomography, bronchoalveolar lavage, biopsy, cytotoxic T cells, disease severity
National Category
Infectious Medicine
Research subject
Infectious Diseases
urn:nbn:se:umu:diva-99103 (URN)978-91-7601-215-4 (ISBN)
Public defence
2015-02-27, E04, byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2015-02-06 Created: 2015-02-04 Last updated: 2015-02-04Bibliographically approved

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Rasmuson, JohanLindqvist, PerSörensen, KarenHedström, MagnusBlomberg, AndersAhlm, Clas
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