Puumala Hantavirus Research Articles

Visual analysis of hot spots and trends in research of meteorology and hemorrhagic fever with renal syndrome: a bibliometric analysis based on CiteSpace and VOSviewer

Objective: We here displayed the global research trends of meteorology and hemorrhagic fever with renal syndrome (HFRS) as a visual knowledge map by using bibliometrics and revealed the research directions, hotspots, trends, and frontiers in this field.Methods: Using Web of Science core collection as the data source and with CiteSpace and VOSviewer software, we collected and analyzed the annual number of papers, cooperative relationships (countries, institutions, authors, etc.), citations (literature citation, literature co-citation, literature publication, etc.), keywords (emergence, clustering, etc.) of meteorology, and HFRS-related research data for the past 30 years, and drew a visual map.Results: In total, this study included 313 papers investigating the relationship between meteorology and HFRS. The first paper was published in 1992. Globally, United States had the largest number of publications in this field, and the Chinese Center for Disease Control and Prevention was the most influential institution conducting related research (20 articles published, and the mediation centrality was 0.24). Several small author cooperation clusters were formed; however, the number of papers published by the same scholar and the co-citation frequency were low. Cazelles Bernard (7 articles) published the highest number of articles in this field, and Gubler DJ was the author with the most co-citations (55 times). The most frequently cited journal was Emerging Infectious Diseases. In this field, the top three high-frequency keywords were “hemorrhagic fever,” “transmission,” and “temperature.” According to keyword cluster analysis, the top three themes were dengue, dechlorane plus, and bank voles. The timeline spectrum exhibited that dengue clustering had a good temporal continuity. The trend analysis of emergent words revealed that the research on “temperature,” “meteorological factors” and “Puumala hantavirus” has gradually appeared in recent years.Conclusion: This study represents the first comprehensive exploration of global trends, hotspots, frontiers, and developments in the relationship between meteorology and HFRS, utilizing CiteSpace and VOSviewer software. The findings of this study are crucial for elucidating the influence of climate change on disease transmission patterns and offering novel insights for forthcoming epidemiological research and public health interventions.

Spread of Puumala Hantavirus to New Areas in a Large Croatian Outbreak of Hemorrhagic Fever with Renal Syndrome, 2021.

Background: The largest documented outbreak of hemorrhagic fever with renal syndrome occurred in Primorje-Gorski Kotar County, Croatia, in 2021, marking the first-time cases of hantavirus infection recorded outside of the known endemic region in the north of the county. Aim: To identify the factors contributing to the spread of the outbreak and to compare risk factors for acquiring hantavirus infection in the endemic and newly affected regions. Methods and Results: A total of 189 cases were confirmed by positive Puumala IgM/IgG antibodies (93.6%), and 13 probable cases were identified by clinical and epidemiological data (6.4%) using a structured questionnaire. Of the 179 cases with available clinical data, 59 (33.0%) were hospitalized. Three cases received hemodialysis, and no deaths were reported. Among 170 cases with information on exposures, 66 (38.8%) reported occupational risk. Cases in the northern part of county were more likely to have been infected in early spring (OR 27.1, 95% CI 2.93-250.7), to report seeing a rodent (OR 6.5; 95%CI 2.3-18.4), and to know someone with hemorrhagic fever with renal syndrome (HFRS) (OR 3.0; 95%CI 1.2-8.0) than cases from the southern part of the county. Data from Croatian Forests Ltd. suggested that an unusually good production of beech seeds in 2020 may have contributed to an increased rodent population in 2021. However, average temperature, rainfall, and humidity data from 2021 did not illustrate a significant difference from previous years (Kruskal-Wallis p = 0.837, p = 0.999, p = 0.108). Conclusion: The 2021 HFRS outbreak was likely fueled by an abundant rodent population and virus transmission in rodent hosts. Human activity, environmental factors, and the ensuing animal-human interactions have spread hantavirus infection from Croatia's mountainous region to a previously nonendemic coastal area with a Mediterranean climate.

Neutrophil-to-lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity.

Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad range of severity and is influenced by direct and immune-mediated effects. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and predicts severity and outcome in various diseases. Therefore, we examined the role of NLR in HFRS caused by hantavirus Puumala (PUUV) and its association with disease severity and kidney injury. We detected elevated NLR levels on admission (NLRadm: median 3.82, range 1.75-7.59), which increased during acute HFRS. Maximum NLR levels (NLRmax: median 4.19, range 1.75-13.16) were 2.38-fold higher compared to the reference NLR level of 1.76 in the general population. NLR levels on admission correlate with markers of severity (length of hospital stay, serum creatinine) but not with other markers of severity (leukocytes, platelets, C-reactive protein, lactate dehydrogenase, serum albumin, proteinuria). Interestingly, levels of nephrin, which is a specific marker of podocyte damage in kidney injury, are highest on admission and correlate with NLRmax, but not with NLRadm. Together, we observed a correlation between systemic inflammation and the severity of HFRS, but our results also revealed that podocyte damage precedes these inflammatory processes.

High-resolution early warning system for human Puumala hantavirus infection risk in Germany

The fluctuation of human infections by the Puumala orthohantavirus (PUUV) in Germany has been linked to weather and phenology parameters that drive the population growth of its host species. We quantified the annual PUUV-outbreaks at the district level by binarizing the reported infections in the period 2006–2021. With these labels we trained a model based on a support vector machine classifier for predicting local outbreaks and incidence well in advance. The feature selection for the optimal model was performed by a heuristic method and identified five monthly weather variables from the previous two years plus the beech flowering intensity of the previous year. The predictive power of the optimal model was assessed by a leave-one-out cross-validation in 16 years that led to an 82.8% accuracy for the outbreak and a 0.457 coefficient of determination for the incidence. Prediction risk maps for the entire endemic area in Germany will be annually available on a freely-accessible permanent online platform of the German Environment Agency. The model correctly identified 2022 as a year with low outbreak risk, whereas its prediction for large-scale high outbreak risk in 2023 was not confirmed.

A simple clinical score to reduce unnecessary testing for Puumala hantavirus.

Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), an endemic form of transient acute renal injury (AKI). Serological testing is the mainstay of diagnosis. It was the aim of the present study to assist decision-making for serological testing by constructing a simple tool that predicts the likelihood of PUUV positivity. We conducted a comparative cohort study of all PUUV-tested cases at Aachen University tertiary care center in Germany between mid-2013 and mid-2021. N = 293 qualified for inclusion; N = 30 had a positive test result and clinical NE; N = 263 were negative. Two predictive point scores, the Aachen PUUV Score (APS) 1 and 2, respectively, were derived with the aid of logistic regression and receiver operating characteristic (ROC) analysis by determining the presence of four admission parameters. For internal validation, the internal Monte Carlo method was applied. In addition, partial external validation was performed using an independent historic cohort of N = 41 positive cases of NE. APS1 is recommended for clinical use as it estimated the probability of PUUV positivity in the entire medical population tested. With a range from 0 to 6 points, it yielded an area under the curve of 0.94 by allotting 2 points each for fever or headache and 1 point each for AKI or LDH>300 U/L. A point sum of 0-2 safely predicted negativity for PUUV, as was confirmed in the NE validation cohort. Here, we present a novel, easy-to-use tool to guide the diagnostic management of suspected PUUV infection/NE and to safely avoid unnecessary serological testing, as indicated by point sum class 0-2. Since 67% of the cohort fell into this stratum, half of the testing should be avoidable in the future.

Direct and indirect effects of Puumala hantavirus on platelet function

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation.Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration.Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome.

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.

Machine learning identifies straightforward early warning rules for human Puumala hantavirus outbreaks

Human Puumala virus (PUUV) infections in Germany fluctuate multi-annually, following fluctuations of the bank vole population size. We applied a transformation to the annual incidence values and established a heuristic method to develop a straightforward robust model for the binary human infection risk at the district level. The classification model was powered by a machine-learning algorithm and achieved 85% sensitivity and 71% precision, despite using only three weather parameters from the previous years as inputs, namely the soil temperature in April of two years before and in September of the previous year, and the sunshine duration in September of two years before. Moreover, we introduced the PUUV Outbreak Index that quantifies the spatial synchrony of local PUUV-outbreaks, and applied it to the seven reported outbreaks in the period 2006–2021. Finally, we used the classification model to estimate the PUUV Outbreak Index, achieving 20% maximum uncertainty.

Fatal Puumala Hantavirus Infection in a Patient with Common Variable Immunodeficiency (CVID)

Puumala hantavirus (PUUV) infections usually show a mild or moderate clinical course, but may sometimes also lead to life-threatening disease. Here, we report on a 60-year-old female patient with common variable immunodeficiency (CVID) who developed a fatal PUUV infection with persistent renal failure, thrombocytopenia, and CNS infection with impaired consciousness and tetraparesis. Hantavirus-specific antibodies could not be detected due to the humoral immunodeficiency. Diagnosis and virological monitoring were based on the quantitative detection of PUUV RNA in blood, cerebrospinal fluid, bronchial lavage, and urine, where viral RNA was found over an unusually extended period of one month. Due to clinical deterioration and virus persistence, treatment with ribavirin was initiated. Additionally, fresh frozen plasma (FFP) from convalescent donors with a history of PUUV infection was administered. Despite viral clearance, the clinical condition of the patient did not improve and the patient died on day 81 of hospitalization. This case underlines the importance of the humoral immune response for the course of PUUV disease and illustrates the need for PCR-based virus diagnostics in those patients. Due to its potential antiviral activity, convalescent plasma should be considered in the therapy of severe hantavirus diseases.

The presence of intraperitoneal, retroperitoneal and pleural fluid in acute Puumala hantavirus infection

Background Puumala hantavirus (PUUV) causes most cases of haemorrhagic fever with renal syndrome (HFRS) in Europe. PUUV infection is characterised by acute kidney injury, thrombocytopenia and increased capillary leakage. Typical symptoms are fever, headache, nausea, abdominal and back pain. This study aimed to evaluate the amount and distribution of intraperitoneal, retroperitoneal and pleural fluid and the association of fluid collections to the symptoms and clinical findings in patients with acute PUUV infection. Methods Abdominal magnetic resonance imaging (MRI) was performed on 27 hospitalised patients with acute PUUV infection. The clinical and laboratory findings and patients’ symptoms were analysed in relation to the imaging findings. The thickness of the fluid collections was measured in millimetres (mm) from axial images. Results Fluid collections were found in all patients. The amount of intraperitoneal fluid correlated positively with plasma C-reactive protein (CRP) level (r = 0.586, p = .001), while it had an inverse correlation with serum creatinine concentration (r = −0.418, p = .030). Retroperitoneal fluid also correlated inversely with serum creatinine and cystatin C concentrations (r = −0.501, p = .008 and r = −0.383, p = .048, respectively). The amount of fluid was not greater in patients with abdominal or back pain. Patients with back pain had higher serum creatinine compared with patients without back pain, 452 µmol/L (range 88–1071) vs. 83 µmol/L (range 60–679), p = .004. Conclusions Fluid collections were found in all patients. A greater amount of intraperitoneal fluid associates with higher CRP concentrations but not with higher serum creatinine levels. Back pain associates with higher creatinine level but not with the presence of fluids.

Условия заражения геморрагической лихорадкой с почечным синдромом населения лесостепного и степного ландшафтов

The studied conditions for infection with hemorrhagic fever with renal syndrome, which occupies a leading place in Russia among all natural focal infections, mainly relate to forest and forest-steppe landscapes, while the conditions for infection of the population in the steppe remain poorly understood. The purpose of the work is to determine the conditions for infection with hemorrhagic fever with renal syndrome in the population of the forest-steppe and steppe landscapes using the example of the Orenburg region. Puumala hantavirus circulates in the region. 731 maps of the epidemiological examination of the epidemic focus of zoonoses were studied. The study showed that in the forest-steppe landscape, in comparison with the steppe, infection of the population occurs more often during work on a personal plot, as well as in everyday life at the place of residence from small mammals or environmental objects. In the steppe landscape, in contrast to the forest-steppe, infection with hantaviruses is more often observed during fishing and when resting in the forest. Keywords: hemorrhagic fever with renal syndrome, forest-steppe and steppe landscapes, infection conditions.

Abdominal CT findings in Puumala hantavirus-infected patients.

Previous clinical studies have reported abdominal findings on ultrasonography or MRI in Puumala hantavirus-infected patients. To determine if abdominal computed tomography (CT) can lead to a diagnosis of Puumala virus infection in the presence of a suggestive clinical picture. CT findings were studied retrospectively in 30 patients who presented to the emergency department of two (Belgian) hospitals with serologically confirmed Puumala hantavirus infection. The most frequent finding was perirenal fascial thickening (90%), followed by perirenal fat stranding (87%). Retroperitoneal fat stranding was found in 19 patients (64%) in the perivesical spaces along the fascia of the external iliac vessels with or without involvement of the presacral fat. Half of the patients had pelvic ascites, and pleural fluid was found in 7 of them. The right and left mean pole-to-pole kidney's lengths were respectively 125.7mm and 127.8mm in 28 patients. Retroperitoneal fat stranding, perirenal fascial thickening and/or perirenal fat stranding were found in most patients with acute Puumala virus infection who have undergone CT. Although nonspecific, these findings may help to suggest Puumala hantavirus infection in the right clinical settings.

Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses.

The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.

Severity Biomarkers in Puumala Hantavirus Infection.

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.

ABO and Rhesus Blood Groups in Acute Puumala Hantavirus Infection.

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.

Hormonal Defects Are Common during Puumala Hantavirus Infection and Associate with Disease Severity and Biomarkers of Altered Haemostasis.

Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.

Coagulopathy in Acute Puumala Hantavirus Infection.

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.

Hantavirus Research in Finland: Highlights and Perspectives.

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.

The Clinical Presentation of Puumala Hantavirus Induced Hemorrhagic Fever with Renal Syndrome Is Related to Plasma Glucose Concentration.

Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome characterized by thrombocytopenia, increased capillary leakage, and acute kidney injury (AKI). As glucosuria at hospital admission predicts the severity of PUUV infection, we explored how plasma glucose concentration associates with disease severity. Plasma glucose values were measured during hospital care in 185 patients with PUUV infection. They were divided into two groups according to maximum plasma glucose concentration: P-Gluc < 7.8 mmol/L (n = 134) and P-Gluc ≥ 7.8 mmol/L (n = 51). The determinants of disease severity were analyzed across groups. Patients with P-Gluc ≥7.8 mmol/L had higher hematocrit (0.46 vs. 0.43; p < 0.001) and lower plasma albumin concentration (24 vs. 29 g/L; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. They presented with higher prevalence of pulmonary infiltrations and pleural effusion in chest radiograph, higher prevalence of shock and greater weight change during hospitalization. Patients with P-Gluc ≥ 7.8 mmol/L were characterized by lower platelet count (50 vs. 66 × 109/L; p = 0.001), more severe AKI (plasma creatinine 272 vs. 151 µmol/L; p = 0.001), and longer hospital treatment (8 vs. 6 days; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. Plasma glucose level is associated with the severity of capillary leakage, thrombocytopenia, inflammation, and AKI in patients with acute PUUV infection.