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The coagulation cascade and fibrinolysis have links with neuroinflammation and increased activation of the coagulation system has been reported in MS patients. We quantified levels of D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and the bioactivity of bacterial lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) and plasma from newly diagnosed untreated MS patients and controls. These molecules showed multiple correlations with each other as well as with age, HLA-DRB1*15:01, body-mass-index and CSF IgG. Our results confirm previous findings of increased plasma PAI-1 and LPS in MS patients compared to controls indicating changes in platelet function and gut permeability in MS.
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Hantaviruses cause the acute zoonotic diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Infected patients show strong systemic inflammation and immune cell activation. NK cells are highly activated in HFRS, suggesting that also other innate lymphoid cells (ILCs) might be responding to infection. Here, we characterized peripheral ILC responses, and measured plasma levels of soluble factors and plasma viral load, in 17 Puumala virus (PUUV)-infected HFRS patients. This revealed an increased frequency of ILC2 in patients, in particular the ILC2 lineage-committed c-Kitlo ILC2 subset. Patients' ILCs showed an activated profile with increased proliferation and displayed altered expression of several homing markers. How ILCs are activated during viral infection is largely unknown. When analyzing PUUV-mediated activation of ILCs in vitro we observed that this was dependent on type I interferons, suggesting a role for type I interferons-produced in response to virus infection-in the activation of ILCs. Further, stimulation of naïve ILC2s with IFN-ß affected ILC2 cytokine responses in vitro, causing decreased IL-5 and IL-13, and increased IL-10, CXCL10, and GM-CSF secretion. These results show that ILCs are activated in HFRS patients and suggest that the classical antiviral type I IFNs are involved in shaping ILC functions.
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Febre Hemorrágica com Síndrome Renal , Imunidade Inata , Interferon Tipo I , Linfócitos , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Imunidade Inata/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Virus Puumala/imunologia , Masculino , Orthohantavírus/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Citocinas/metabolismo , Citocinas/imunologiaRESUMO
Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.
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Febre Hemorrágica com Síndrome Renal , Neutrófilos , Virus Puumala , Trombocitopenia , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Neutrófilos/imunologia , Humanos , Trombocitopenia/imunologia , Trombocitopenia/virologia , Virus Puumala/imunologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Ativação de Neutrófilo , IdosoRESUMO
BACKGROUND AND OBJECTIVES: Epstein-Barr virus (EBV) infection is a major risk factor of multiple sclerosis (MS). We examined the presence of EBV DNA in the CSF and blood of patients with MS and controls. We analyzed whether EBV DNA is more common in the CSF of patients with MS than in controls and estimated the proportions of EBV-positive B cells in the CSF and blood. METHODS: CSF supernatants and cells were collected at diagnostic lumbar punctures from 45 patients with MS and 45 HLA-DR15 matched controls with other conditions, all participants were EBV seropositive. Cellular DNA was amplified by Phi polymerase targeting both host and viral DNA, and representative samples were obtained in 28 cases and 28 controls. Nonamplified DNA from CSF cells (14 cases, 14 controls) and blood B cells (10 cases, 10 controls) were analyzed in a subset of participants. Multiple droplet digital PCR (ddPCR) runs were performed per sample to assess the cumulative EBV positivity rate. To detect viral RNA as a sign of activation, RNA sequencing was performed in blood CD4-positive, CD8-positive, and CD19-positive cells from 21 patients with MS and 3 controls. RESULTS: One of the 45 patients with MS and none of the 45 controls were positive for EBV DNA in CSF supernatants (1 mL). CSF cellular DNA was analyzed in 8 independent ddPCRs: EBV DNA was detected at least once in 18 (64%) of the 28 patients with MS and in 15 (54%) of the 28 controls (p = 0.59, Fisher test). The cumulative EBV positivity increased steadily up to 59% in the successive ddPCRs, suggesting that all individuals would have reached EBV positivity in the CSF cells, if more DNA would have been analyzed. The estimated proportion of EBV-positive B cells was >1/10,000 in both the CSF and blood. We did not detect viral RNA, except from endogenous retroviruses, in the blood lymphocyte subpopulations. DISCUSSION: EBV-DNA is equally detectable in the CSF cells of both patients with MS and controls with ddPCR, and the probabilistic approach indicates that the true positivity rate approaches 100% in EBV-positive individuals. The proportion of EBV-positive B cells seems higher than previously estimated.
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Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Humanos , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , DNA Viral , RNA ViralRESUMO
INTRODUCTION: Hantaviruses cause two kinds of clinical syndromes. Hemorrhagic fever with renal syndrome is caused by Hantaan virus in Asia, Puumala virus (PUUV) and Dobrava virus in Europe, and Seoul virus worldwide. Hantavirus cardiopulmonary syndrome is caused by Sin Nombre virus in North America and Andes virus and related viruses in Latin America. All hantaviruses are carried by rodents and insectivores. Humans are infected via inhaled aerosols of rodent excreta. In the history, there are several epidemics of acute infectious diseases during many wars, which have been suggested or proven to be caused by various hantaviruses. MATERIALS AND METHODS: Literature review of 41 original publications and reviews published between 1943 and 2022 was performed. Among them, 23 publications handle hantavirus infections among military forces, and the rest 17 hantavirus infections themselves. RESULTS: A large epidemic during World War II in 1942 among German and Finnish soldiers in Northern Finland with more than 1,000 patients was most probably caused by PUUV. During Korean War in 1951-1954,â¼ 3,200 cases occurred among United Nations soldiers in an epidemic caused by Hantaan virus. During Balkan war from 1991 to 1995, numerous soldiers got ill because of hantavirus infection caused by PUUV and Dobrava virus. Several other reports of cases of various hantavirus infections especially among U.S. soldiers acting in South Korea, Germany, Bosnia, and Kosovo have been described in the literature. CONCLUSIONS: Military maneuvers usually include soil removal, spreading, digging with accompanied dust, and living in field and other harsh conditions, which easily expose soldiers to rodents and their excreta. Therefore, the risks of hantavirus infections in military context are obvious. All military infections have been caused by hantaviruses leading to hemorrhagic fever with renal syndrome.
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Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Militares , Orthohantavírus , Animais , Humanos , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/complicações , Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/etiologia , RoedoresRESUMO
Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
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Transtornos Psicóticos , Humanos , Biomarcadores , Interleucina-6 , Análise Multivariada , Transtornos Psicóticos/metabolismoRESUMO
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.
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Injúria Renal Aguda , Infecções por Vírus Epstein-Barr , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Virus Puumala , Humanos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Infecções por Hantavirus/complicaçõesRESUMO
Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Antígenos Virais , Doença Crônica , Epitopos , Humanos , Pandemias , SARS-CoV-2RESUMO
Eight decades ago, a report on "a swamp fever-like disease in German troups in Lapland" was published in this journal. The disease outbreak had occurred in 1942 and affected more than 1000 soldiers at the Finish front. The published, precise analysis of the clinical picture was obviously the first description of hantavirus disease in the German language area. Nowadays, hantavirus disease - in Central and Northern Europe also known as Nephropathia epidemica - is one of the most frequent notifiable virus diseases in Germany and Finland.
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Doenças Transmissíveis , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Humanos , Idioma , II Guerra Mundial , Febre Hemorrágica com Síndrome Renal/epidemiologia , Surtos de Doenças , Infecções por Hantavirus/diagnóstico , Infecções por Hantavirus/epidemiologiaRESUMO
Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.
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Injúria Renal Aguda , Febre Hemorrágica com Síndrome Renal , Virus Puumala , Anticorpos Neutralizantes , Humanos , Índice de Gravidade de DoençaRESUMO
Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Finlândia/epidemiologia , Humanos , SARS-CoV-2/genéticaRESUMO
Old-world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus-caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS-associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus-infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus-infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.
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Injúria Renal Aguda , Febre Hemorrágica com Síndrome Renal , Virus Puumala , Células Endoteliais , Glucuronidase , Febre Hemorrágica com Síndrome Renal/complicações , Humanos , Proteinúria/etiologia , Índice de Gravidade de DoençaRESUMO
Several viral infections are associated with acute and long-term complications. During the past two years, there have been many reports on post-infectious symptoms of the patients suffering from COVID-19 disease. Serious complications occasionally occur during the acute phase of Puumala orthohantavirus caused nephropathia epidemica. Severe long-term consequences are rare. Fatigue for several weeks is quite common. Hormonal insufficiencies should be excluded if the patient does not recover normally.
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COVID-19 , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Virus Puumala , Infecções por Hantavirus/complicações , Febre Hemorrágica com Síndrome Renal/complicações , HumanosRESUMO
BACKGROUND: Major cardiac events including myocardial infarction (MI) are associated with viral infections. However, how specific infections contribute to the cardiovascular insults has remained largely unclear. METHODS: We employed next generation phage display mimotope-variation analysis (MVA) to explore the link between antibody-based immune response and severe cardiovascular conditions. Here, we used a case-control design, including the first-stage discovery cohort (n = 100), along with cohorts for second-stage discovery (n = 329) and validation (n = 466). FINDINGS: We observed strong antibody response to the peptide antigens with Gly-Ile-X-Asp (G-I-X-D) core structure in healthy individuals but not in patients with MI. Analysis of the origin of this epitope linked it with the N-terminus of the VP1 protein of poliovirus 3 (PV3), but also other species of picornaviruses. Consistently, we found low levels of antibody response to the G-I-X-D epitope in individuals with severe cardiac disease complications. INTERPRETATION: Our findings imply that antibody response to the G-I-X-D epitope is associated with polio vaccinations and that high antibody levels to this epitope could discriminate healthy individuals from prospective MI patients as a blood-derived biomarker. Together, these findings highlight the importance of epitope-specific antibody response and suggest that protective immunity against the polio- and non-polio enteroviral infections support improved cardiovascular health. FUNDING: Estonian Ministry of Education (5.1-4/20/170), Estonian Research Council (PRG573, PRG805), H2020-MSCA-RISE-2016 (EU734791), H2020 PANBioRA (EU760921), European Union through the European Regional Development Fund (Project no. 2014-2020.4.01.15-0012), Helsinki University Hospital grants, Mary and Georg C. Ehrnrooth Foundation, Finnish Eye Foundation, Finska Läkaresällskapet, The Finnish Society of Sciences and Letters, Magnus Ehrnrooth Foundation and Sigrid Jusélius Foundation.
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Doenças Cardiovasculares , Poliovirus , Capsídeo , Proteínas do Capsídeo , Epitopos , Humanos , Imunidade , Estudos ProspectivosRESUMO
Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. We aimed to evaluate whether ABO and rhesus blood groups associate with the susceptibility or the severity of PUUV infection. We analyzed blood groups in 289 adult patients treated in Tampere University hospital due to PUUV infection during the years 1982-2017. Patients' blood group distribution was compared to that of healthy, voluntary blood donors living in the Tampere University Hospital responsibility area (n = 21,833). The severity of PUUV infection, as judged by the severity of acute kidney injury (AKI), thrombocytopenia, inflammation, capillary leakage, and the length of hospital care, was analyzed across the groups. The ABO and rhesus blood group distributions did not differ between the patients and blood donors. Patients with non-O blood groups had lower systolic blood pressure compared to patients with blood group O, but there was no difference in other markers of capillary leakage or in the severity of AKI. Minor deviations in the number of platelets and leukocytes were detected between the O and non-O blood groups. To conclude, patients with blood group O may be less susceptible to hypotension, but otherwise blood groups have no major influences on disease susceptibility or severity during acute PUUV infection.
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Sistema ABO de Grupos Sanguíneos , Febre Hemorrágica com Síndrome Renal/sangue , Sistema do Grupo Sanguíneo Rh-Hr , Injúria Renal Aguda/sangue , Adulto , Síndrome de Vazamento Capilar/sangue , Suscetibilidade a Doenças , Feminino , Febre Hemorrágica com Síndrome Renal/diagnóstico , Humanos , Hipotensão/sangue , Masculino , Pessoa de Meia-Idade , Virus Puumala/patogenicidade , Índice de Gravidade de DoençaRESUMO
The function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC-derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase-Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS-specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)-responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
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Transtorno do Espectro Autista , Síndrome do Cromossomo X Frágil , Células-Tronco Pluripotentes Induzidas , Animais , Astrócitos/metabolismo , Transtorno do Espectro Autista/metabolismo , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1009400.].
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Finland has the highest incidence of hantavirus infections globally, with a significant impact on public health. The large coverage of boreal forests and the cyclic dynamics of the dominant forest rodent species, the bank vole Myodes glareolus, explain most of this. We review the relationships between Puumala hantavirus (PUUV), its host rodent, and the hantavirus disease, nephropathia epidemica (NE), in Finland. We describe the history of NE and its diagnostic research in Finland, the seasonal and multiannual cyclic dynamics of PUUV in bank voles impacting human epidemiology, and we compare our northern epidemiological patterns with those in temperate Europe. The long survival of PUUV outside the host and the life-long shedding of PUUV by the bank voles are highlighted. In humans, the infection has unique features in pathobiology but rarely long-term consequences. NE is affected by specific host genetics and risk behavior (smoking), and certain biomarkers can predict the outcome. Unlike many other hantaviruses, PUUV causes a relatively mild disease and is rarely fatal. Reinfections do not exist. Antiviral therapy is complicated by the fact that when symptoms appear, the patient already has a generalized infection. Blocking vascular leakage measures counteracting pathobiology, offer a real therapeutic approach.
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Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/virologia , Orthohantavírus/genética , Pesquisa , Doenças dos Roedores/virologia , Animais , Anticorpos Antivirais/sangue , Arvicolinae/virologia , Europa (Continente)/epidemiologia , Finlândia/epidemiologia , Orthohantavírus/imunologia , Orthohantavírus/patogenicidade , Infecções por Hantavirus/imunologia , Infecções por Hantavirus/transmissão , Humanos , Incidência , Fatores de Risco , Doenças dos Roedores/transmissão , Estações do AnoRESUMO
Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein-kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.