Fig 1.
Study flow diagram summarizing patient identification, exclusion and subsequent analysis.
Absolute number of patients as indicated.
Fig 2.
Patient demographics stratified by acute Puumala hantavirus infection (PUUV) status.
Positives indicated in red, negatives in blue. (A) Perennial and seasonal cumulative case incidences of years mid-2013 to mid-2021. (B) Medical specialties involved in the initial diagnostic management and instigation of serological testing. (C). Durations of prodromal symptoms and lengths of stay. Data are medians with interquartile ranges. (D) Compilation of final diagnoses. Abbreviations: AKI, acute kidney injury as defined by KDIGO/Kidney Disease: Improving Global Outcomes; AKI, other, AKI of neither GN/Vasculitic, nor pre-, or postrenal etiology; Emergency, emergency department; Gastro, gastroenterology; GN/Vasculitis, glomerulonephritis and vasculitis; Heart/Lung, cardiology and pulmonary medicine; Hem/Onc, hematology and oncology; Intensive, intensive care unit; Infection, other, neither bacterial nor viral cause identified; Infection, other viral, viral infection not caused by influenza; MOF, multiple organ failure; N, absolute number of patients available for analysis; NE, nephropathia epidemica; Nephro, nephrology; PUUV, acute Puumala hantavirus infection status. Statistics: Analyzed group sizes were N = 30 and N = 263 for positives and negatives, respectively, except N = 25 and N = 127, respectively, for prodromal length. Two-tailed t-test with Welch’s correction; *p≤0.05, ***≤0.001.
Table 1.
Study Population and admission parameters.
Table 2.
Study population outcome parameters.
Table 3.
Contingency tables of diagnostic hit rate and PUUV score class by medical specialty.
Fig 3.
Statistical evaluation of symptoms (A) and laboratory abnormalities (B) on admission–hantavirus positives and negatives indicated by red and blue linework, respectively. Abbreviations: CRP, C-reactive protein; KDIGO AKI, acute kidney injury as defined by Kidney Disease: Improving Global Outcomes; LDH, lactate dehydrogenase; N, absolute number of patients available for analysis; PCT, procalcitonin; PUUV, acute Puumala hantavirus infection status; WBC, white blood count. Statistical testing: Fisher‘s exact test; **p≤0.01, ***≤0.001.
Fig 4.
Construction and partial validation of two alternative scores for the prediction of PUUV positivity.
(A-C) Aachen PUUV Score (APS) 1, derived using the complete control group of heterogeneous mixed diagnoses. (A’-C’) APS2, derived using a control group consisting of only confirmed other viral infections. (A, A’) Basic information and scoring tables on the assignment of score points per criterium. (B, B’) Receiver operating and the corresponding test characteristics of sensitivity, specificity, and accuracy. (C, C’) Results tables displaying for each point sum class its i) corresponding estimated probability of PUUV positivity and the actual PUUV positivity ii) the occurrence of point sum classes in a cumulated fashion in the complete cohort. (D, D’) Partial score validation of APS1 and APS2. Use of an independent historic cohort of N = 41 PUUV-positive-only subjects with acute hantavirus infection from the years 2001–2012. Population characteristics as indicated in S2 Table. Shown are occurrences of point sum classes. Importantly, point sum class 0–1 predicted (C, C’) and confirmed (D, D’) a 0–5% probability of PUUV positivity in both scores, as highlighted in green shade, thus defining it as a rule-out criterium. In APS1, point sum class 2 was also associated with a very low mean probability of PUUV positivity of 3% and thus also highlighted in green shade. Highlighted in red shade are point sum classes associated with predicting or confirming a >90% probability of positivity. Abbreviations: Acc, accuracy; AKI, acute kidney injury according to KIDIGO/Kidney Disease: Improving Global Outcomes; AUC, area under the curve; LDH, lactate dehydrogenase; N, absolute number of patients per group; PUUV, acute Puumala hantavirus infection status; in brackets: confidence intervals. Sens, sensitivity; Spec, specificity.
Fig 5.
Diagnosis-specific comparison of the key follow-up parameters platelet minimum (A) and creatinine maximum (B). Hantavirus group is shown on top, highlighted in red. Abbreviations: AKI, acute kidney injury as defined by KDIGO/Kidney Disease: Improving Global Outcomes; AKI other, AKI of neither GN/Vasculitic, nor prerenal, or postrenal etiology; GN/Vasculitis, glomerulonephritis and vasculitis; Infection, other, neither bacterial nor viral cause identified; Infection, other, viral, viral infection not caused by influenza; MOF, multiple organ failure; N, absolute number of patients per group. Statistical testing: ANOVA; *p≤0.05, **≤0.01, ***≤0.001.