Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study

Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study Huan Wang, Sisi Fang, Hua Wang, Xin Zheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7866935/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 7 You are reading this latest preprint version Abstract Objective Severe fever with thrombocytopenia syndrome (SFTS) is a viral infectious disease characterized by high mortality. Calcium dysregulation is implicated in viral replication and host immune response. We aimed to evaluate the association between serum calcium levels and in-hospital mortality in patients with SFTS. Methods In this retrospective cohort study, we enrolled 809 laboratory-confirmed SFTS patients admitted between April 2017 and June 2024. Hypocalcemia was defined as corrected calcium < 8.12 mg/dL. Multivariate logistic regression, restricted cubic spline (RCS), and longitudinal analyses were employed to assess associations between serum calcium and mortality. Results The in-hospital mortality rate was 11.87% (96/809). Hypocalcemia was observed in 72.68% of patients (588/809) with SFTS upon admission. Multivariate logistic regression analysis revealed that lower serum calcium was an independent predictor of in-hospital mortality, alongside older age, neurological symptoms, higher viral loads, lower albumin levels, elevated creatinine, and prolonged activated partial thromboplastin time (APTT). Restricted cubic spline (RCS) analysis revealed a significant L-shaped association between serum calcium levels and in-hospital mortality, with a critical inflection point at 7.56 mg/dL. Dynamic analysis showed that serum calcium levels increased and normalized by day 6 in survivors but peaked and declined thereafter in non-survivors. Hypocalcemia was independently associated with hypoalbuminemia, hypoglobulinemia, hyponatremia, and monocytopenia. Furthermore, serum calcium levels were inversely correlated with viral load, creatine kinase, APTT, IL-6, and IL-10 (all p < 0.05). Conclusions Hypocalcemia is exceedingly common in SFTS patients and serves as a robust, independent prognostic marker for in-hospital mortality. Its association with high viral replication and host inflammatory response underscores its clinical significance. Serial monitoring of serum calcium could enhance risk stratification and guide management decisions in SFTS. severe fever with thrombocytopenia syndrome serum calcium mortality Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV), has been officially named Dabie bandavirus (DBV), which belongs to the Bunyavirales order , Phenuiviridae family , and Bandavirus genus ( 1 ). SFTS was first identified in China in 2009 and rapidly spread in South Korea, Japan, the USA, Vietnam, Myanmar and Taiwan( 2 – 7 ). It is characterized by hemorrhagic fever, thrombocytopenia, leukocytopenia, neurological complications, electrolyte imbalances, multiple organ failure, and eventually death, with a fatality rate of 12%-50%( 8 ). Due to its high mortality rate and the possibility of an outbreak of as a global pandemic, SFTS was declared one of the priority infectious diseases by the WHO in 2018( 9 ). Ribavirin, favipiravir (T-705), and calcium channel blockers have been previously reported for their antiviral effects against SFTSV( 8 , 10 , 11 ). Nonetheless, to date, no effective vaccines or antiviral agents have been approved for the treatment of SFTSV infection. Hence, identifying the risk factors associated with mortality and taking early action are crucial for decreasing the death rate among SFTS patients. Calcium is a vital element that plays a critical role in various physiological functions. It is crucial for maintaining proper cardiac function, facilitating muscle contractions, ensuring the structural integrity of bones, and serving as a signaling molecule in various biochemical pathways. Calcium ions (Ca 2+ ) act as second messengers within mammalian cells involved in the regulation of almost all cellular processes and play a fundamental role in viral replication mechanisms, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), COVID-19, Ebola viruses, Dengue fever, hepatitis B virus, and SFTSV( 11 – 16 ). Previous study by Li et al. revealed that calcium channel blocker benidipine hydrochloride inhibit SFTSV infection through reducing cellular Ca 2+ uptake( 11 ). Thus, alterations in calcium homeostasis might play a role in the disease severity and mortality in patients with SFTS. Hypocalcemia has been identified as a risk factor associated with increased mortality in patients with COVID-19, Ebola, Dengue fever and SFTS( 11 , 17 – 19 ). Previous studies indicated that the incidence of hypocalcemia in COVID-19 patients range from 59.3% to 76.6% and found that total calcium ≤ 2.02 mmol/L or 8.38 mg/dL had increased risk of in-hospital mortality( 17 , 20 , 21 ). Several studies found that hypocalcemia was also associated with increased mortality in non-viral infectious diseases such as acute pulmonary thromboembolism, heart failure and chronic kidney disease ( 22 , 23 ). The mechanisms underlying this may involve pro-inflammatory cytokine release, end-organ resistance to parathyroid hormone, vitamin D deficiency or insufficiency( 24 ). To the best of our knowledge, there have been very few studies investigating serum calcium levels and the risk of death in SFTS patients( 11 ). However, these two studies only investigated the impact of serum calcium on prognosis without considering the influence of albumin on serum calcium levels. Moreover, they did not provide the optimal critical value of serum calcium for estimating the disease severity or data on the dynamic changes in serum calcium levels during hospitalization. Our study aimed to investigate the prevalence of hypocalcemia in SFTS patients upon hospital admission, evaluate the association between serum calcium levels and clinical outcomes, analyze dynamic changes in serum calcium levels during hospitalization, and determine the optimal critical threshold of serum calcium for assessing disease severity. These findings may facilitate early identification of high-risk patients and guide timely clinical interventions to improve prognosis. Patients and methods Patients and Data Collection A total of 816 laboratory-confirmed SFTS patients admitted to the Department of Infectious Diseases at Wuhan Union Hospital from April 2017 to June 2024 were retrospectively analyzed. Laboratory confirmation of SFTS required meeting one or more of the following criteria: (a) detection of SFTSV RNA in the patient’s serum; (b) detection of IgM antibodies against SFTSV or a four-fold increase in serum IgG antibodies during the convalescent phase; or (c) detection of the SFTSV genome via next-generation sequencing. After excluding 7 patients with missing serum calcium records, 809 patients were ultimately included in the study. Patients were stratified into three groups based on serum calcium levels: G1 <7.0 mg/dL (n = 59), 7.0 ≤ G2<8.12 (n = 529), G3 ≥ 8.12 (n = 221) (see S1 Fig). Two trained physicians retrospectively collected data on demographics, underlying diseases, clinical characteristics, laboratory findings, comorbidities, and overall prognosis from medical records. Statistical Analysis All statistical analyses were conducted using R (version 4.4.0; R Foundation for Statistical Computing, Vienna, Austria). Continuous variables were presented as median (1st Quartile, 3st Quartile) or mean (± standard deviation). Significant differences between two groups were assessed using the Student’s t-test or the nonparametric two-tailed Mann-Whitney U test. Categorical variables were expressed as percentages (%), and significant differences between two groups were analyzed using the chi-square test or Fisher’s exact test. Differences among multiple groups were determined using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Multivariate logistic regression analyses were used to identify independent risk factors for mortality and corrected calcium levels. Survival analysis, stratified by corrected calcium levels across the four groups, was performed using Kaplan-Meier (KM) curves with the log-rank test. Restricted cubic splines (RCS) were used to further investigate the association between calcium levels and SFTS mortality. The dynamic changes in serum calcium levels, tracked from admission to discharge or death, were visualized using locally weighted scatterplot smoothing (LOESS). The relationships between serum calcium levels and viral load, creatine kinase, and APTT, IL-6, IL-10, CD4 + T cell at hospital admission were assessed using linear regression models to evaluate the strength and significance of these associations. All statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant. Results Baseline characteristics of the study population. As shown in Table 1 , a total of 809 patients were enrolled in this study, of whom 96 (11.87%) died during hospitalization. The median age of the study population was 63 years (interquartile range [IQR]: 55–70), with 342 (42.27%) male participants. Major comorbidities included hypertension in 191 patients (23.61%), diabetes mellitus in 93 (11.50%), chronic obstructive pulmonary disease (COPD) in 33 (4.08%), and chronic hepatitis B (CHB) in 83 (10.26%). Neurological and hemorrhagic manifestations occurred in 26.70% and 12.48% of cases, respectively. The median hospital stay was 9 days (interquartile range [IQR]: 7–12), with 21 cases (2.60%) requiring intensive care unit (ICU) transfer. Patients were stratified into survival (n = 713) and non-survival (n = 96) groups based on clinical outcomes. Comparative analysis revealed significant between-group differences, non-survivors were older than survivors (median age 70 [IQR 62–75] vs. 62 [IQR 54–69] years; P < 0.001) and had higher hypertension prevalence (40.61% [39/96] vs. 21.32% [152/713]; P < 0.001). No intergroup differences were detected in sex distribution (P = 0.472), diabetes mellitus (P = 0.356), chronic obstructive pulmonary disease (COPD; P = 0.621), or chronic hepatitis B (CHB; P = 0.843) prevalence. Notably, the non-survival group demonstrated significantly higher frequencies of neurological manifestations (67.71% vs. 21.18%, P < 0.001), hemorrhagic manifestations (20.83% vs. 11.36%, P = 0.008), and ICU transfer (9.38% vs. 1.68%, P < 0.001). Table 1 Baseline Characteristics and Laboratory Parameters in Patients With SFTS Variables Total (n = 809) Survivors (n = 713) Non-survivors (n = 96) P Age (y) 63.00 (55.00, 70.00) 62.00 (54.00, 69.00) 70.00 (63.00, 73.25) < 0.0001 Sex, male (%) 342 (42.27%) 301 (42.22%) 41 (42.71%) 0.927 Comorbidity Hypertension 191 (23.61%) 152 (21.32%) 39 (40.61%) < 0.0001 Diabetes 93 (11.50%) 81 (11.36%) 12 (12.50%) 0.7424 COPD 33 (4.08%) 28 (3.93%) 5 (5.21%) 0.7482 CHB 83 (10.26%) 78 (10.94%) 5 (5.21%) 0.0823 Complications Neurological symptoms 216 (26.70%) 151 (21.18%) 65 (67.71%) < 0.0001 Hemorrhagic signs 101 (12.48%) 81 (11.36%) 20 (20.83%) 0.0084 Laboratory parameters Calcium 7.80 (7.48, 8.16) 7.84 (7.52, 8.16) 7.48 (7.00, 7.82) < 0.0001 Albumin 31.74 ± 4.48 31.91 ± 4.45 30.41 ± 4.48 0.002 Corrected Calcium 8.45 (8.17, 8.76) 8.48 (8.20, 8.78) 8.22 (7.81, 8.56) < 0.0001 Viral load (Log10) 3.07(2.06, 4.11) 2.91(2.00, 3.80) 5.07 (4.11, 5.72) < 0.0001 WBC 2.85 (1.76, 4.78) 2.90 (1.78, 4.90) 2.39 (1.68, 4.04) 0.1302 RBC 4.20 (3.82, 4.60) 4.20 (3.82, 4.61) 4.22 (3.89, 4.54) 0.6886 Hb 126.00(115.00, 139.00) 125.00(115.00, 139.00) 127.50 (116.00, 139.00) 0.4417 PLT 50.00 (34.00, 64.00) 51.00 (36.00, 66.00) 35.50 (24.00, 49.25) < 0.0001 Lymphocyte 0.69 (0.44, 1.22) 0.70 (0.45, 1.26) 0.57 (0.33, 0.96) 0.0032 Monocyte 0.16 (0.08, 0.37) 0.18 (0.08, 0.39) 0.095 (0.058, 0.173) < 0.0001 Neutrophil 1.64 (0.95, 3.17) 1.69 (0.92, 3.26) 1.51 (1.08, 2.77) 0.907 ALT 80.00(48.00, 142.00) 77.00 (47.00, 129.00) 118.50 (62.75, 195.75) 0.0003 AST 185.00 (101.00, 362.00) 174.0000 (95.00, 321.00) 409.00 (222.25, 690.50) < 0.0001 Tbil 9.40 (7.00, 12.80) 9.40 (6.90, 12.80) 9.95 (7.18, 13.05) 0.2994 TP 57.40 (53.30, 61.30) 57.50 (53.40, 61.40) 56.95 (52.15, 60.93) 0.4013 Globulin 25.30 (22.80, 28.40) 25.20 (22.60, 28.20) 25.8500 (23.98, 29.90) 0.0168 Creatinine 70.00 (58.00, 85.20) 68.60 (57.20, 82.48) 90.2500 (70.10, 148.03) < 0.0001 BUN 4.82 (3.45, 6.58) 4.6200 (3.34, 6.20) 7.56 (5.53, 11.04) < 0.0001 LDH(Log10) 2.88 (2.69, 3.09) 2.86 (2.67, 3.05) 3.13 (2.90, 3.35) < 0.0001 CK(Log10) 2.70 (2.36, 3.11) 2.67 (2.33, 3.07) 3.08(2.63, 3.32) < 0.0001 cTnI 106.00 (44.10, 555.80) 97.70 (40.30, 447.90) 227.10 (92.23, 688.82) < 0.0001 CKMB 4.70 (1.90, 7.03) 4.50 (1.80, 6.74) 6.28 (3.28, 9.28) < 0.0001 Sodium 135.60 (133.00, 138.20) 135.60 (133.10, 138.20) 135.40 (132.25, 138.50) 0.4116 Potassium 3.63 (3.30, 3.94) 3.60 (3.29, 3.91) 3.96 (3.53, 4.22) < 0.0001 Magnesium 0.78 (0.68, 0.86) 0.78 (0.69, 0.86) 0.75 (0.68, 0.83) 0.1325 Phosphorus 0.90 (0.76, 1.08) 0.90 (0.76, 1.07) 0.95 (0.79, 1.17) 0.0206 APTT 50.20 (42.70, 59.80) 48.90 (41.70, 57.40) 67.60 (55.30, 83.83) < 0.0001 D-dimer 2.90 (1.40, 5.09) 2.57 (1.31, 4.75) 5.01 (2.98, 10.32) < 0.0001 FIB 2.49 (2.05, 2.97) 2.50 (2.08, 3.02) 2.41 (1.97, 2.78) 0.07 INR 1.03 (0.94, 1.15) 1.02 (0.94, 1.14) 1.09 (1.00, 1.22) 0.0006 PT 13.20 (12.40, 14.40) 13.10 (12.30, 14.30) 13.70 (13.00, 15.03) < 0.0001 TT 24.40 (20.40, 31.30) 23.70 (20.10, 29.20) 40.20 (26.66, 62.25) < 0.0001 Outcomes Hospital stay 9.00 (7.00, 12.00) 10.00 (8.00, 12.00) 3.00 (2.00, 4.00) < 0.0001 ICU transfer 21 (2.60%) 12 (1.68%) 9 (9.38%) < 0.0001 Abbreviations and normal range: SFTS, severe fever with thrombocytopenia syndrome; COPD, chronic obstructive pulmonary disease; CHB, chronic hepatitis B; ICU, intensive care unit; Calcium, 8.12-10.16mg/dL(2.03-2.54mmol/L); Albumin, 35-55g/L; Corrected calcium, 8.5–10.2 mg/dL; Viral load, < 100TCID50/ml; WBC, white blood cell, 3.5–9.5×10 9 /L; RBC, red blood cell, 3.8–5.1×10 12 /L; Hb, hemoglobin, 115-150g/L; PLT, platelet,125–350×10 9 /L; ALT, alanine aminotransferase, 5-35U/L; AST, aspartate aminotransferase, 8-40U/L; TBIL, total bilirubin, 5.1-19umol/L; TP, total protein, 64-83g/L; Globulin, 20-30g/L; Creatinine, 44-106umol/L; BUN, blood urea nitrogen, 2.9-8.2mmol/L; LDH, lactate dehydrogenase, 109-245U/L; CK, Creatine kinase, 38-174U/L; cTnI, cardiac troponin I, < 26.2ng/L; CKMB, Creatine Kinase MB, < 6.6ng/L; Sodium, 136-145mmol/L; Potassium, 3.5-5.2mmol/L, Magnesium, 0.7-1.1mmol/L; Phosphorus, 0.96-1.62mmol/L; APTT, activated partial thromboplastin time, 28-43.5s; D-dimer, <0.5ug/mL FEU; FEU, fibrinogen equivalent unit; FIB, fibrinogen, 2.0-4.0g/L; INR, international normalized ratio, 0.8–1.2; PT, prothrombin time, 11-14.2s; TT, thrombin time, 14-21s. Laboratory findings revealed that non-survivors had significantly lower levels of serum albumin, calcium, corrected calcium, platelet count (PLT), lymphocyte count, and monocyte count compared to survivors (all p < 0.05). Conversely, non-survivors showed significantly higher levels of viral load; liver function biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST]); renal function biomarkers (creatinine, blood urea nitrogen [BUN]); myocardial injury-related biomarkers (creatine kinase, lactate dehydrogenase [LDH], cTnI, creatine kinase-MB [CK-MB]); coagulation parameters (APTT, D-dimer, international normalized ratio [INR], prothrombin time [PT], thrombin time [TT]); and potassium (all p < 0.05). Among the 809 patients with SFTS, lymphocyte subsets (sTable1) were analyzed in 78 cases (9.6%; survival group: n = 71, non-survival group: n = 7), and cytokine profiles (sTable2) were assessed in 239 cases (29.5%; survival group: n = 214, non-survival group: n = 25). Comparative analysis revealed significant immunological differences between the two groups. The survival group exhibited higher absolute counts of B lymphocytes (B cells), CD3 + T cells, CD4 + T cells, and CD8 + T cells compared to the non-survival group. In contrast, natural killer (NK) cell counts were lower in survivors. The most pronounced differences were observed in CD3 + T cells, CD4 + T cells, and CD8 + T cell populations (P < 0.05 for all). Non-survivors demonstrated significantly elevated levels of pro-inflammatory and anti-inflammatory cytokines, including IFN-γ, IL-10, IL-4, and IL-6. Conversely, TNF-α and IL-2 levels were lower in non-survivors. The most marked differences were observed in IFN-γ, IL-10, and IL-6 (P < 0.05). The association between serum calcium and clinical outcomes. Univariate and multivariate logistic regression analysis on the risk factors associated with mortality of SFTS (Table 2 ) demonstrated that lower serum calcium as an independent predictor for in-hospital mortality, along with older age, neurological symptoms, higher viral loads, lower albumin and elevated creatinine. Table 3 summarizes the baseline characteristics of all patients stratified by calcium levels. The cohorts were divided into three groups based on baseline corrected calcium levels: G1 <7.0 mg/dL, 7.0 mg/dL ≤ G2<8.12 mg/dL, G3 ≥ 8.12 mg/dL, comprising 59, 529, and 221 patients, respectively. Patients with lower calcium levels were predominantly older, male and exhibited higher rates of neurological symptoms, hemorrhagic signs, ICU admission, and mortality. No significant intergroup differences were observed in comorbidities such as hypertension, diabetes, COPD, and CHB. Mortality, viral load, renal function biomarkers (creatinine and blood urea nitrogen), and coagulation parameters (APTT, D-dimer, fibrinogen [FIB], INR, and PT) were negatively correlated with calcium levels (all p < 0.05). In contrast, lymphocyte and monocyte counts were positively correlated with calcium levels (p < 0.05). Table 2 Univariate and multivariate logistic regression analysis on the risk factors associated with mortality of SFTS Univariate Multivariate OR (95%CI) P OR (95%CI) P Calcium (mg/dL) 0.23 (0.15 ~ 0.35) < .001 0.26 (0.10 ~ 0.66) 0.005 Age 1.09 (1.06 ~ 1.12) < .001 1.13 (1.06 ~ 1.20) < .001 Neurological symptoms 7.80 (4.91 ~ 12.41) < .001 7.91 (3.21 ~ 19.48) < .001 Viral load (Log10) 3.50 (2.73 ~ 4.49) < .001 2.24 (1.44 ~ 3.49) < .001 Albumin 0.93 (0.88 ~ 0.97) 0.002 1.18 (1.03 ~ 1.35) 0.017 Creatinine 1.02 (1.01 ~ 1.02) < .001 1.02 (1.01 ~ 1.02) < .001 APTT 1.06 (1.05 ~ 1.07) < .001 1.04 (1.01 ~ 1.08) 0.033 Hemorrhagic signs 2.05 (1.19 ~ 3.54) 0.01 0.58 (0.14 ~ 2.33) 0.444 Hypertension 2.53 (1.62 ~ 3.94) < .001 1.33 (0.49 ~ 3.58) 0.571 PLT 0.97 (0.95 ~ 0.98) < .001 0.97 (0.95 ~ 1.00) 0.075 Monocyte 0.22 (0.08 ~ 0.64) 0.005 0.61 (0.15 ~ 2.44) 0.48 AST 1.01 (1.01 ~ 1.01) < .001 1.00 (1.00 ~ 1.00) 0.959 LDH(Log10) 31.14 (13.48 ~ 71.94) < .001 1.98 (0.11 ~ 34.59) 0.639 CK(Log10) 2.56 (1.71 ~ 3.82) < .001 0.45 (0.12 ~ 1.67) 0.233 cTnI 1.01 (1.01 ~ 1.01) < .001 1.00 (1.00 ~ 1.00) 0.229 CK-MB 1.05 (1.03 ~ 1.07) < .001 1.01 (0.96 ~ 1.06) 0.693 Table 3 Characteristics and outcomes of SFTS patients categorized by calcium on admission baseline Calcium P G1 <7.0 (n = 59) 7.0 ≤ G2<8.12 (n = 529) G3 ≥ 8.12 (n = 221) Characteristic Age, M (Q₁, Q₃) 66.00 (57.00,71.00) 63.00 (56.00,70.00) 62.00 (54.00,67.00) 0.01 Sex, n(%) 38 (64.41) 216 (40.83) 88 (39.82) 0.002 Comorbidity Neurological symptoms, n(%) 24 (40.68) 151 (28.54) 41 (18.55) < .001 Hemorrhagic signs, n(%) 14 (23.73) 62 (11.72) 25 (11.31) 0.025 Complications Hypertension, n(%) 16 (27.12) 125 (23.63) 50 (22.62) 0.77 Diabetes, n(%) 4 (6.78) 67 (12.67) 22 (9.95) 0.284 COPD, n(%) 4 (6.78) 20 (3.78) 9 (4.07) 0.543 CHB, n(%) 5 (8.47) 55 (10.40) 23 (10.41) 0.896 Laboratory parameters Viral load (Log10) 3.94 (3.11,5.02) 3.16 (2.26,4.11) 2.51 (1.44,3.57) < .001 WBC 2.71 (1.88,4.50) 2.81 (1.70,4.78) 2.95 (1.88,4.91) 0.464 RBC 4.26 (3.82,4.76) 4.16 (3.82,4.57) 4.27 (3.88,4.71) 0.166 Hb 127.00 (113.00,142.00) 125.00 (115.00,139.00) 127.00 (116.00,139.00) 0.539 PLT 40.00 (27.00,53.00) 48.00 (34.00,61.00) 57.00 (39.00,79.00) < .001 Lymphocyte 0.63 (0.41,1.28) 0.64 (0.41,1.08) 0.90 (0.50,1.46) < .001 Monocyte 0.11 (0.06,0.28) 0.15 (0.08,0.33) 0.22 (0.10,0.46) < .001 Neutrophil 1.97 (1.23,2.65) 1.66 (0.93,3.38) 1.59 (0.92,2.95) 0.647 ALT 117.00 (68.00,180.00) 83.00 (49.00,151.00) 67.00 (45.00,113.00) < .001 AST 333.00 (169.00,703.00) 205.00 (109.00,388.00) 138.00 (79.00,231.00) < .001 Tbil 9.50 (7.95,12.50) 9.00 (6.80,12.40) 10.30 (7.80,13.40) 0.005 TP 54.40 (50.70,58.95) 56.25 (52.80,60.02) 60.60 (56.70,64.60) < .001 Albumin 28.60 (25.50,31.80) 31.10 (28.30,33.70) 34.20 (30.90,37.50) < .001 Globulin 25.20 (22.40,28.85) 25.10 (22.50,27.90) 26.05 (23.48,29.30) 0.013 Creatinine 88.85 (68.85,127.50) 68.45 (57.90,85.45) 65.50 (55.95,80.70) < .001 BUN 6.01 (4.49,9.38) 4.81 (3.45,6.50) 4.56 (3.29,6.40) < .001 LDH(Log10) 3.09 (2.89,3.28) 2.89 (2.72,3.12) 2.76 (2.58,2.96) < .001 CK(Log10) 3.12 (2.71,3.44) 2.71 (2.40,3.09) 2.55 (2.16,2.89) < .001 cTnI 107.70 (68.05,419.10) 85.30 (41.50,227.67) 59.30 (21.80,125.20) < .001 CK-MB 6.20 (2.20,12.15) 3.25 (1.60,6.70) 2.80 (1.20,5.40) < .001 Calcium 6.72 (6.56,6.88) 7.64 (7.44,7.88) 8.36 (8.20,8.60) < .001 Sodium 135.40 (131.70,137.95) 135.20 (132.60,137.70) 137.10 (134.20,140.20) < .001 Potassium 3.78 (3.28,4.11) 3.60 (3.29,3.93) 3.67 (3.37,3.96) 0.127 Magnesium 0.71 (0.65,0.80) 0.76 (0.67,0.84) 0.80 (0.73,0.89) < .001 Phosphorus 0.99 (0.77,1.12) 0.87 (0.73,1.04) 0.93 (0.78,1.12) 0.002 APTT 63.50 (50.95,81.43) 51.10 (44.60,60.70) 43.35 (37.88,51.78) < .001 D-dimer 4.17 (2.92,8.62) 2.71 (1.45,5.21) 1.56 (0.91,3.38) < .001 FIB 2.20 (1.71,2.54) 2.47 (2.05,2.89) 2.73 (2.22,3.10) < .001 INR 1.11 (1.03,1.23) 1.02 (0.94,1.12) 1.00 (0.93,1.10) < .001 PT 14.10 (13.20,15.30) 13.10 (12.40,14.20) 12.80 (12.20,13.90) < .001 TT 37.40 (22.70,59.00) 24.60 (20.60,31.40) 21.80 (18.83,26.90) < .001 Outcomes Fatality, n(%) 22 (37.29) 63 (11.91) 11 (4.98) < .001 Hospitalstay 9.00 (3.50,13.00) 10.00 (7.00,12.00) 9.00 (6.00,11.00) 0.02 ICUtransfer, n(%) 5 (8.47) 14 (2.65) 2 (0.90) 0.005 G1, comprising 59 cases, was associated with significantly higher mortality (37.29%) and an increased likelihood of ICU transfer (8.47%). This group also exhibited the highest levels of viral load; liver function biomarkers (ALT, AST, and total bilirubin [Tbil]); renal function biomarkers (creatinine and BUN); myocardial injury-related biomarkers (LDH, creatine kinase, and CK-MB); and coagulation function biomarkers (APTT, D-dimer, INR, PT, and TT) (all p < 0.05), the lowest level of PLT, lymphocyte, monocyte, albumin and magnesium (all p < 0.05). Patients in G3 exhibited the lowest mortality rate (4.98%) and ICU transfer rate (0.9%), had the mildest clinical conditions, characterized by the highest lymphocyte and monocyte counts, the lowest levels of viral load, the lowest levels of renal function biomarkers (creatinine and BUN) and coagulation function biomarkers (APTT, D-dimer, INR, PT, and TT) (all p < 0.05). Kaplan-Meier survival analysis results are presented in S1 Fig, demonstrating significant divergence in survival probabilities among the three groups (p < 0.001). Hypocalcemia was significantly associated with an increased risk of 28-day all-cause mortality. The highest survival rate was observed in G3, while the lowest survival rate was found in G1. RCS analysis (Fig. 1 A) revealed a significant L-shaped association between serum calcium levels and in-hospital mortality. The mortality risk sharply decreased with increasing calcium levels until reaching an inflection point at 7.5628 mg/dL upon admission (p for nonlinearity = 0.733). Below this threshold, each unit decrease in calcium was associated with a marked elevation in mortality risk. However, above the cut-off value of 7.5628 mg/dL, the mortality risk plateaued and no longer demonstrated significant variation with further increases in corrected calcium levels. A similar relationship was observed in Fig. 1 B, where the mortality risk sharply decreased with increasing corrected calcium levels until reaching an inflection point at 8.4532 mg/dL upon admission (p for nonlinearity = 0.725). Dynamic change of serum calcium during hospitalization. We conducted a kinetic analysis of calcium, albumin, and corrected calcium levels, tracking their changes from day 1 to day 28 or or until discharge after admission (see Fig. 2 ). The trajectories of calcium, albumin, and corrected calcium levels from day 1 to day 12 or until discharge after admission are shown in Fig. 3 . At each time point, the calcium and albumin levels in the survival group were consistently higher than those in the non-survival group. Except for the 6-8th days after admission, the corrected calcium levels in the survival group were consistently higher than those in the non-survival group at all other time points. In the survival group, serum calcium showed an upward trend and reached the normal range by the 6th day after admission. While it gradually increased, reaching its peak on the 6th day and then gradually decreased in the non-survival group. Potential factors associated with low serum calcium. Univariate and multivariate logistic regression analyses of factors associated with hypocalcemia are presented in Table 4 . To further investigate the characteristics associated with hypocalcemia in SFTS patients, we stratified the cohort by admission serum calcium levels into a hypocalcemia group (calcium < 8.12 mg/dL) and a normocalcemia group (calcium ≥ 8.12 mg/dL). Patients with hypocalcemia were significantly older and exhibited higher viral loads, elevated levels of AST, creatinine, BUN, LDH, CK, CK-MB, and prolonged APTT. Conversely, the hypocalcemia group demonstrated significantly lower PLT, lymphocyte and monocyte counts, TP, albumin, magnesium, and sodium levels. Multivariate logistic regression analysis identified several independent factors significantly associated with hypocalcemia at admission. These included lower albumin levels (OR = 0.80, p < 0.001), lower globulin levels (OR = 0.93, p = 0.002), lower sodium levels (OR = 0.93, p = 0.002), and lower monocyte counts (OR = 0.48, p = 0.05). These findings indicate that hypoalbuminemia, hypoglobulinemia, hyponatremia, and monocytopenia represent independent risk factors for hypocalcemia in SFTS patients. Linear regression analysis (Fig. 4 ) revealed statistically significant inverse associations between serum calcium levels and viral loads (R² = 0.0695, p < 0.001), CK (R² = 0.0875, p < 0.001), APTT (R² = 0.1097, p < 0.001), IL-6 (R² = 0.0172, p < 0.0432), IL-10 (R² = 0.0323, p < 0.0053). These findings suggest that hypocalcemia was independently associated with higher viral load, myocardial injury (indicated by CK elevation), coagulation dysfunction (indicated by prolonged APTT), and cytokine storm (reflected by elevated IL-6 and IL-10 levels) in patients with SFTS. Table 4 Univariate and multivariate logistic regression analysis of risk factors associated with hypocalcemia Univariate Multivariate OR (95%CI) P OR (95%CI) P Albumin 0.82 (0.79 ~ 0.86) < .001 0.80 (0.76 ~ 0.85) < .001 Globulin 0.95 (0.92 ~ 0.98) 0.002 0.93 (0.89 ~ 0.97) 0.002 Sodium 0.90 (0.87 ~ 0.94) < .001 0.93 (0.88 ~ 0.98) 0.003 Monocyte 0.42 (0.26 ~ 0.66) < .001 0.48 (0.23 ~ 0.99) 0.050 Age 1.02 (1.01 ~ 1.04) 0.007 1.00 (0.98 ~ 1.02) 0.810 Viral load(Log10) 1.34 (1.20 ~ 1.49) < .001 1.12 (0.95 ~ 1.32) 0.177 PLT 0.99 (0.99 ~ 0.99) < .001 1.01 (1.00 ~ 1.01) 0.139 Lymphocyte 0.65 (0.52 ~ 0.82) < .001 0.89 (0.60 ~ 1.32) 0.568 AST 1.01 (1.01 ~ 1.01) < .001 1.00 (1.00 ~ 1.00) 0.513 Creatinine 1.01 (1.01 ~ 1.01) 0.006 1.01 (1.00 ~ 1.02) 0.121 BUN 1.07 (1.01 ~ 1.13) 0.012 0.98 (0.88 ~ 1.09) 0.715 CK(Log10) 2.40 (1.76 ~ 3.29) < .001 1.08 (0.71 ~ 1.66) 0.719 Magnesium 0.10 (0.03 ~ 0.29) < .001 0.34 (0.08 ~ 1.40) 0.137 APTT 1.04 (1.03 ~ 1.06) < .001 1.01 (0.99 ~ 1.02) 0.514 Discussion This study explored the relationship between serum calcium levels, their dynamic changes, and in-hospital mortality in patients with SFTS. Our results demonstrate that hypocalcemia is prevalent among SFTS patients upon admission and is significantly associated with the development of neurological symptoms. Furthermore, serum calcium levels emerged as an independent predictor of mortality, alongside other well-established risk factors such as older age, neurological symptoms, higher viral loads, lower albumin, elevated creatinine, and prolonged APTT. These findings underscore the importance of monitoring and managing calcium levels in SFTS patients to improve clinical outcomes. Our study enrolled 809 SFTS patients, with a mortality rate of 11.87%, consistent with previous reports that mortality in SFTS ranges from 10% to 30%( 25 ). Hypocalcemia was observed in 72.68% of patients upon admission, indicating its high prevalence in SFTS. This finding aligns with studies on COVID-19, SARS and Ebola viruses, which have also identified hypocalcemia as a common feature in critically ill patients.( 11 , 17 , 19 ). Hypocalcemia was observed in 60–75% of COVID-19 patients, 60% of SARS patients, and a similar proportion of Ebola virus disease patients( 26 – 28 ), which was similar with our study. Currently, there is very limited research on serum calcium in SFTS. Only one retrospective study from China found that serum calcium levels were an independent protective factor against in-hospital mortality in SFTS patients( 29 ). Our study found that calcium levels were strongly associated with the development of neurological symptoms and mortality, suggesting that hypocalcemia may play a pathogenic role in SFTS progression, likely due to its role in cellular signaling, muscle contraction, and coagulation( 30 ). RCS analysis revealed a significant L-shaped association between serum calcium levels and in-hospital mortality, indicating that both severe hypocalcemia and hypercalcemia may be detrimental, but the risks are more pronounced at lower calcium levels, particularly when serum calcium <7.5628 mg/dL. Consistent with previous studies on acute myocardial infarction( 31 ). The dynamic analysis further supported this observation, showing that serum calcium levels in the survival group consistently increased and normalized by the 6th day after admission, whereas in the non-survival group, calcium levels peaked on the 6th day and then declined. Monitoring and maintaining adequate calcium levels in all hospitalized patients with SFTS is recommended. Hypocalcemia is also seen in several viral infections, such as Ebola virus, dengue fever, and COVID-19( 17 , 28 , 32 ). The potential causes of hypocalcemia in SFTS patients may include the following( 8 , 33 – 36 ): (a) Most SFTS patients experience severe anorexia, nausea, vomiting, and diarrhea, leading to reduced calcium intake and increased excretion; (b) Calcium is primarily bound to plasma albumin, and decreased serum albumin levels can contribute to hypocalcemia; (c) The SFTS virus may directly damage cells, disrupting calcium ion metabolism; (d) Excessive immune and inflammatory responses may cause calcium metabolism disorders, resulting in hypocalcemia; (e) The virus may impair kidney function, affecting calcium reabsorption and vitamin D activation; (f) Medications used in treatment, such as antivirals or antibiotics, may interfere with calcium metabolism; (g) Viral infection may impact the secretion of parathyroid hormone and vitamin D, leading to abnormal calcium metabolism. The dynamic analysis in our study revealed that serum calcium and albumin levels in non-survivors were consistently lower than those in the survivor group. Serum calcium levels were negatively correlated with viral load and renal function markers (creatinine and BUN) and positively correlated with lymphocyte and monocyte counts. Our findings support the above hypothesis. Thus, early correction of hypocalcemia and hypoproteinemia has been suggested to improve survival, as dynamic studies show that normalized calcium and albumin levels correlate with better outcomes. The linear correlation analysis revealed that hypercalcemia was associated with higher viral load, myocardial injury, coagulation dysfunction, and cytokine storm, providing insights into the potential mechanisms underlying the poor outcomes associated with hypocalcemia. Calcium is essential for maintaining cellular homeostasis, and its deficiency may exacerbate viral replication, impair cardiac function, potentially contributing to neurological symptoms such as seizures or altered mental status, and disrupt coagulation pathways( 37 – 40 ). These findings align with the known pathophysiology of SFTS, which involves widespread endothelial damage, immune dysregulation, and multi-organ dysfunction( 41 ). Hypocalcemia may thus serve as both a marker of disease severity and a contributor to the pathogenic cascade in SFTS. Additionally, the interplay between calcium levels and other biomarkers, such as viral load, cardiac troponin I, APTT and IL-6 warrants further investigation to better understand the complex pathophysiology of SFTS. Our study found that over half of SFTS patients exhibited hypocalcemia upon admission, and lower serum calcium levels were associated with a significantly increased mortality risk. Specifically, when serum calcium levels fell below 7.56 mg/dL or corrected calcium levels dropped below 8.45 mg/dL, mortality rates rose markedly. Appropriate management of this imbalance will be useful in the treatment of SFTS patients. A pilot study conducted in Mexico involving a cohort of dengue-infected patients demonstrated that oral supplementation with calcium carbonate (CaCO₃) combined with vitamin D₃ significantly enhanced platelet count, improved clinical outcomes, and reduced the duration of disease( 42 , 43 ). However, in the context of sepsis management, calcium supplementation has been shown to lack clinical efficacy and may pose potential risks to patient outcomes( 44 ). For SFTS, there is currently no available data regarding the effects of calcium supplementation in patients with hypocalcemia. Recent studies reported that SFTSV infection induces progressive Ca2 + influx, which can be effectively inhibited by benidipine hydrochloride administration. This treatment not only enhances viral clearance and improves clinical outcomes but also leads to a significant reduction in case fatality rates( 11 , 37 ). Research findings on COVID-19 further corroborated this observation, showing that therapeutic intervention with amlodipine besylate, a calcium channel blocker, led to a decreased case fatality rate among patients( 45 ). Therefore, future research should prioritize elucidating the pathophysiological mechanisms underlying the association between hypocalcemia and adverse clinical outcomes in SFTS. Well-designed prospective studies are warranted to evaluate whether early therapeutic interventions, including calcium supplementation or calcium channel blockers (CCBs), can improve survival rates and reduce disease-related complications in this patient population. This study has several limitations. First, it is a single-center study, and the findings may not be generalizable to other populations, future multicenter studies are necessary to validate our findings. Second, while the study demonstrates associations between calcium levels and outcomes, it does not establish causality. Mechanistic studies are needed to elucidate the underlying pathways linking hypocalcemia to virus replication, myocardial injury, coagulation dysfunction, and cytokine storm in SFTS. Finally, the study did not evaluate the impact of calcium supplementation or other interventions on clinical outcomes, which should be explored in future trials. Declarations Ethics approval and consent to participate The clinical study was reviewed and successfully approved by the institutional review board of Tongji Medical College (2023-S093). The study was conducted in accordance with the principles of the Helsinki declaration of 1975, as revised in 1983.The requirement for getting written informed consent was waived due to the retrospective nature of the study. Availability of data : The original data generated in this analysis are available from the corresponding author on reasonable request. Conflict of interests : The authors declare that they have no competing interests. Funding : The work was supported by grants from the National Key R&D Program of China (2022YFC2305100) and the National Science and Technology Major Project of China (grant 92169121). Authors' contributions : Huan Wang performed the study, data collection, and wrote the article. Sisi Fang contributed to data analysis. Hua Wang contributed to data collection. Xin Zheng was responsible for designing the study, revising the article, and securing funding. Acknowledgements : Not applicable. References Casel MA, Park SJ, Choi YK. Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy. Experimental & Molecular Medicine. 2021;53(5):713-22. doi: 10.1038/s12276-021-00610-1. Yu X-J, Liang M-F, Zhang S-Y, Liu Y, Li J-D, Sun Y-L, et al. Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China. New England Journal of Medicine. 2011;364(16):1523-32. doi: 10.1056/NEJMoa1010095. Kim YR, Yun Y, Bae SG, Park D, Kim S, Lee JM, et al. Severe Fever with Thrombocytopenia Syndrome Virus Infection, South Korea, 2010. Emerging Infectious Diseases. 2018;24(11):2103-5. doi: 10.3201/eid2411.170756. Takahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, et al. The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan. The Journal of Infectious Diseases. 2014;209(6):816-27. doi: 10.1093/infdis/jit603. McMullan LK, Folk SM, Kelly AJ, MacNeil A, Goldsmith CS, Metcalfe MG, et al. A new phlebovirus associated with severe febrile illness in Missouri. The New England journal of medicine. 2012;367(9):834-41. Epub 2012/08/31. doi: 10.1056/NEJMoa1203378. PubMed PMID: 22931317. Win AM, Nguyen YTH, Kim Y, Ha NY, Kang JG, Kim H, et al. Genotypic Heterogeneity of Orientia tsutsugamushi in Scrub Typhus Patients and Thrombocytopenia Syndrome Co-infection, Myanmar. Emerg Infect Dis. 2020;26(8):1878-81. Epub 2020/07/21. doi: 10.3201/eid2608.200135. PubMed PMID: 32687023; PubMed Central PMCID: PMCPMC7392420. Lin T-L, Ou S-C, Maeda K, Shimoda H, Chan JP-W, Tu W-C, et al. The first discovery of severe fever with thrombocytopenia syndrome virus in Taiwan. Emerging Microbes & Infections. 2020;9(1):148-51. doi: 10.1080/22221751.2019.1710436. Li H, Lu Q-B, Xing B, Zhang S-F, Liu K, Du J, et al. Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011–17: a prospective observational study. The Lancet Infectious Diseases. 2018;18(10):1127-37. doi: 10.1016/s1473-3099(18)30293-7. Schoch CL, Ciufo S, Domrachev M, Hotton CL, Kannan S, Khovanskaya R, et al. NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database. 2020;2020. doi: 10.1093/database/baaa062. Li H, Jiang X-M, Cui N, Yuan C, Zhang S-F, Lu Q-B, et al. Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome. Signal Transduction and Targeted Therapy. 2021;6(1). doi: 10.1038/s41392-021-00541-3. Li H, Zhang L-K, Li S-F, Zhang S-F, Wan W-W, Zhang Y-L, et al. Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality. Cell Research. 2019;29(9):739-53. doi: 10.1038/s41422-019-0214-z. Straus MR, Tang T, Lai AL, Flegel A, Bidon M, Freed JH, et al. Ca 2+ Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity. Journal of Virology. 2020;94(13). doi: 10.1128/jvi.00426-20. Berlansky S, Sallinger M, Grabmayr H, Humer C, Bernhard A, Fahrner M, et al. Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies. Cells. 2022;11(2). doi: 10.3390/cells11020253. Nathan L, Lai AL, Millet JK, Straus MR, Freed JH, Whittaker GR, et al. Calcium Ions Directly Interact with the Ebola Virus Fusion Peptide To Promote Structure–Function Changes That Enhance Infection. ACS Infectious Diseases. 2019;6(2):250-60. doi: 10.1021/acsinfecdis.9b00296. Shivanthan M, Rajapakse S. Dengue and Calcium. International Journal of Critical Illness and Injury Science. 2014;4(4). doi: 10.4103/2229-5151.147538. Kong F, Zhang F, Liu X, Qin S, Yang X, Kong D, et al. Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target. Cell Communication and Signaling. 2021;19(1). doi: 10.1186/s12964-021-00762-7. Minasi A, Andreadi A, Maiorino A, Giudice L, De Taddeo S, D’Ippolito I, et al. Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19. Endocrine. 2022;79(3):577-86. doi: 10.1007/s12020-022-03239-w. van Griensven J, Bah EI, Haba N, Delamou A, Camara BS, Olivier KJ-J, et al. Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015. Emerging Infectious Diseases. 2016;22(12). doi: 10.3201/eid2212.161136. Constantine GR, Rajapakse S, Ranasinghe P, Parththipan B, Wijewickrama A, Jayawardana P. Hypocalcemia is associated with disease severity in patients with dengue. The Journal of Infection in Developing Countries. 2014;8(09):1205-9. doi: 10.3855/jidc.4974. Raesi A, Saedi Dezaki E, Moosapour H, Saeidifard F, Habibi Z, Rahmani F, et al. Hypocalcemia in Covid-19: A Prognostic Marker for Severe Disease. Iranian journal of pathology. 2021;16(2):144-53. Epub 2021/05/04. doi: 10.30699/ijp.2020.130491.2442. PubMed PMID: 33936225; PubMed Central PMCID: PMCPMC8085287. Torres B, Alcubilla P, González-Cordón A, Inciarte A, Chumbita M, Cardozo C, et al. Impact of low serum calcium at hospital admission on SARS-CoV-2 infection outcome. International Journal of Infectious Diseases. 2021;104:164-8. doi: 10.1016/j.ijid.2020.11.207. Yang Yq, Wang X, Zhang Yj, Chen Yf, Wang L, Hu Xw, et al. Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism. Respirology. 2022;27(8):645-52. doi: 10.1111/resp.14243. Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, et al. Association of Hypocalcemia With Mortality in Hospitalized Patients With Heart Failure and Chronic Kidney Disease. Journal of Cardiac Failure. 2015;21(8):621-7. doi: 10.1016/j.cardfail.2015.04.015. Hendy GN, Canaff L. Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis. Seminars in cell & developmental biology. 2016;49:37-43. Epub 2015/11/28. doi: 10.1016/j.semcdb.2015.11.006. PubMed PMID: 26612442. Cui H, Shen S, Chen L, Fan Z, Wen Q, Xing Y, et al. Global epidemiology of severe fever with thrombocytopenia syndrome virus in human and animals: a systematic review and meta-analysis. The Lancet Regional Health - Western Pacific. 2024;48:101133. doi: 10.1016/j.lanwpc.2024.101133. Osman W, Al Fahdi F, Al Salmi I, Al Khalili H, Gokhale A, Khamis F. Serum Calcium and Vitamin D levels: Correlation with severity of COVID-19 in hospitalized patients in Royal Hospital, Oman. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;107:153-63. Epub 2021/04/24. doi: 10.1016/j.ijid.2021.04.050. PubMed PMID: 33892191; PubMed Central PMCID: PMCPMC8057687. Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. Jama. 2003;289(21):2801-9. Epub 2003/05/08. doi: 10.1001/jama.289.21.JOC30885. PubMed PMID: 12734147. Uyeki TM, Mehta AK, Davey RT, Jr., Liddell AM, Wolf T, Vetter P, et al. Clinical Management of Ebola Virus Disease in the United States and Europe. The New England journal of medicine. 2016;374(7):636-46. Epub 2016/02/18. doi: 10.1056/NEJMoa1504874. PubMed PMID: 26886522; PubMed Central PMCID: PMCPMC4972324. Zang yan. Prognostic Value of Serum Calcium Levels in Severe Fever with Thrombocytopenia Syndrome. Advances in Clinical Medicine. 2024;14(05):133-41. doi: 10.12677/acm.2024.1451407. Saurav S, Tanwar J, Ahuja K, Motiani RK. Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance. Molecular Aspects of Medicine. 2021;81. doi: 10.1016/j.mam.2021.101004. Schmitz T, Thilo C, Linseisen J, Heier M, Peters A, Kuch B, et al. Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry. Scientific reports. 2021;11(1):2476. Epub 2021/01/30. doi: 10.1038/s41598-021-81929-7. PubMed PMID: 33510279; PubMed Central PMCID: PMCPMC7843683. Constantine GR, Rajapakse S, Ranasinghe P, Parththipan B, Wijewickrama A, Jayawardana P. Hypocalcemia is associated with disease severity in patients with dengue. Journal of infection in developing countries. 2014;8(9):1205-9. Epub 2014/09/13. doi: 10.3855/jidc.4974. PubMed PMID: 25212087. Yang T, Huang H, Jiang L, Li J. Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (Review). International journal of molecular medicine. 2022;50(3). Epub 2022/07/21. doi: 10.3892/ijmm.2022.5174. PubMed PMID: 35856413; PubMed Central PMCID: PMCPMC9333902. Cappellini F, Brivio R, Casati M, Cavallero A, Contro E, Brambilla P. Low levels of total and ionized calcium in blood of COVID-19 patients. Clinical chemistry and laboratory medicine. 2020;58(9):e171-e3. Epub 2020/05/28. doi: 10.1515/cclm-2020-0611. PubMed PMID: 32459190. Sun JK, Zhang WH, Zou L, Liu Y, Li JJ, Kan XH, et al. Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019. Aging. 2020;12(12):11287-95. Epub 2020/06/27. doi: 10.18632/aging.103526. PubMed PMID: 32589164; PubMed Central PMCID: PMCPMC7343468. Albert SG, Scott Isbell T. Reconsideration of "Albumin corrected total calcium" Determinations: Potential errors in the Clinical management of disorders of calcium metabolism. Clinica chimica acta; international journal of clinical chemistry. 2023;544:117353. Epub 2023/04/20. doi: 10.1016/j.cca.2023.117353. PubMed PMID: 37076097. Urata S, Yoshikawa R, Yasuda J. Calcium Influx Regulates the Replication of Several Negative-Strand RNA Viruses Including Severe Fever with Thrombocytopenia Syndrome Virus. J Virol. 2023;97(3):e0001523. Epub 2023/02/17. doi: 10.1128/jvi.00015-23. PubMed PMID: 36794941; PubMed Central PMCID: PMCPMC10062178. Nathan L, Lai AL, Millet JK, Straus MR, Freed JH, Whittaker GR, et al. Calcium Ions Directly Interact with the Ebola Virus Fusion Peptide To Promote Structure-Function Changes That Enhance Infection. ACS infectious diseases. 2020;6(2):250-60. Epub 2019/11/21. doi: 10.1021/acsinfecdis.9b00296. PubMed PMID: 31746195; PubMed Central PMCID: PMCPMC7040957. Fang D, Chen H. Association between serum calcium level and in-hospital mortality in patients with acute myocardial infarction: a retrospective cohort study. Scientific reports. 2022;12(1). doi: 10.1038/s41598-022-24566-y. Deluque AL, Dimke H, Alexander RT. Biology of calcium homeostasis regulation in intestine and kidney. Nephrology Dialysis Transplantation. 2024;40(3):435-45. doi: 10.1093/ndt/gfae204 %J Nephrology Dialysis Transplantation. Saijo M. Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2018;24(10):773-81. Epub 2018/08/14. doi: 10.1016/j.jiac.2018.07.009. PubMed PMID: 30098914. Cabrera-Cortina JI, Sánchez-Valdéz E, Cedas-DeLezama D, Ramírez-González MD. Oral calcium administration attenuates thrombocytopenia in patients with dengue fever. Report of a pilot study. Proceedings of the Western Pharmacology Society. 2008;51:38-41. Epub 2008/01/01. PubMed PMID: 19544672. Sánchez-Valdéz E, Delgado-Aradillas M, Torres-Martínez JA, Torres-Benítez JM. Clinical response in patients with dengue fever to oral calcium plus vitamin D administration: study of 5 cases. Proceedings of the Western Pharmacology Society. 2009;52:14-7. Epub 2009/01/01. PubMed PMID: 22128411. Collage RD, Howell GM, Zhang X, Stripay JL, Lee JS, Angus DC, et al. Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase kinase signaling. Crit Care Med. 2013;41(11):e352-60. Epub 2013/07/28. doi: 10.1097/CCM.0b013e31828cf436. PubMed PMID: 23887235; PubMed Central PMCID: PMCPMC3812408. Zhang LK, Sun Y, Zeng H, Wang Q, Jiang X, Shang WJ, et al. Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension. Cell discovery. 2020;6(1):96. Epub 2020/12/23. doi: 10.1038/s41421-020-00235-0. PubMed PMID: 33349633; PubMed Central PMCID: PMCPMC7752915. Additional Declarations No competing interests reported. Supplementary Files S1S2Fig.docx sTable12.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 26 Jan, 2026 Reviews received at journal 21 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers invited by journal 25 Nov, 2025 Editor assigned by journal 16 Oct, 2025 Submission checks completed at journal 16 Oct, 2025 First submitted to journal 15 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":376630,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRestricted cubic spline models depicting the relationship between calcium levels and mortality risk in SFTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA, calcium upon admission; B, corrected calcium value upon admission. The relative frequency of corrected calcium/calcium is represnted by the blue bars. The 95% CI of the adjusted odds ratio (OR) is represented by the red-shaded areas.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; OR, odds ratios;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/4db738f9758ca0ac833e4050.png"},{"id":97142134,"identity":"05758d10-eff6-4718-acd3-df26b0338688","added_by":"auto","created_at":"2025-12-01 10:07:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":524941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKinetics of corrected calcium, calcium, albumin between the survivors and non-survivors during hospitalization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA, calcium; B,corrected calcium; B, albumin. All parameters were analyzed at different time intervals for the entire hospital stay. The black solid line represents median of reference parameters, The LLNof reference parameters were depicted with a black dotted line. Three asterisk (***) indicates p ＜0.001, two asterisks (**) indicate p ＜0.01, one asterisks (*) indicate p ＜0.05. LLN=lower limit of normal.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/4558548acf390100f10fc229.png"},{"id":97127953,"identity":"b705debd-814d-4717-b373-e15679068a00","added_by":"auto","created_at":"2025-12-01 08:32:56","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":224202,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDynamic profile of calcium, albumin, and corrected calcium between survivors and non-survivors in patients with SFTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA, calcium; B, corrected calcium; C, albumin. All parameters were analyzed at different time intervals for the entire hospital stay. The LLNof reference parameters were depicted with a black dotted line. LLN, lower level of normal\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/013641cba816034eb5ccdfc3.png"},{"id":97141979,"identity":"7bb31726-9219-4a9c-b414-683c9915896b","added_by":"auto","created_at":"2025-12-01 10:07:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":342985,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLow calcium levels are associated with high viremia, myocardial damage, coagulation disorder, cytokine storm and T-cell immunodeficiency in patients with SFTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLinear correlation between calcium and viral load (A), creatine kinase (B), APTT (C), IL-6 (D), IL-10 (E), CD4\u003csup\u003e+\u003c/sup\u003eT cell (F) in serum\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/878bd41b2a3ab164b6c0d403.png"},{"id":97145426,"identity":"f37b0122-7ed5-4228-8168-e8e4252ffe02","added_by":"auto","created_at":"2025-12-01 10:13:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2966021,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/ba934588-3d4d-4ea3-ae9d-c12e2a0f6ff8.pdf"},{"id":97142813,"identity":"4071fe59-bb34-465b-951c-9ee9dd2e9182","added_by":"auto","created_at":"2025-12-01 10:07:58","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":184772,"visible":true,"origin":"","legend":"","description":"","filename":"S1S2Fig.docx","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/958801645e92266bdf17c1fb.docx"},{"id":97141736,"identity":"d24622f8-1c1c-4522-93a4-7b5345af8756","added_by":"auto","created_at":"2025-12-01 10:06:55","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16721,"visible":true,"origin":"","legend":"","description":"","filename":"sTable12.docx","url":"https://assets-eu.researchsquare.com/files/rs-7866935/v1/c7737f61aae9956c222ffbe0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSevere fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV), has been officially named \u003cem\u003eDabie bandavirus\u003c/em\u003e (DBV), which belongs to the \u003cem\u003eBunyavirales order\u003c/em\u003e, \u003cem\u003ePhenuiviridae family\u003c/em\u003e, and \u003cem\u003eBandavirus genus\u003c/em\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). SFTS was first identified in China in 2009 and rapidly spread in South Korea, Japan, the USA, Vietnam, Myanmar and Taiwan(\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). It is characterized by hemorrhagic fever, thrombocytopenia, leukocytopenia, neurological complications, electrolyte imbalances, multiple organ failure, and eventually death, with a fatality rate of 12%-50%(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Due to its high mortality rate and the possibility of an outbreak of as a global pandemic, SFTS was declared one of the priority infectious diseases by the WHO in 2018(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Ribavirin, favipiravir (T-705), and calcium channel blockers have been previously reported for their antiviral effects against SFTSV(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Nonetheless, to date, no effective vaccines or antiviral agents have been approved for the treatment of SFTSV infection. Hence, identifying the risk factors associated with mortality and taking early action are crucial for decreasing the death rate among SFTS patients.\u003c/p\u003e\u003cp\u003eCalcium is a vital element that plays a critical role in various physiological functions. It is crucial for maintaining proper cardiac function, facilitating muscle contractions, ensuring the structural integrity of bones, and serving as a signaling molecule in various biochemical pathways. Calcium ions (Ca\u003csup\u003e2+\u003c/sup\u003e) act as second messengers within mammalian cells involved in the regulation of almost all cellular processes and play a fundamental role in viral replication mechanisms, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), COVID-19, Ebola viruses, Dengue fever, hepatitis B virus, and SFTSV(\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Previous study by Li et al. revealed that calcium channel blocker benidipine hydrochloride inhibit SFTSV infection through reducing cellular Ca\u003csup\u003e2+\u003c/sup\u003e uptake(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Thus, alterations in calcium homeostasis might play a role in the disease severity and mortality in patients with SFTS.\u003c/p\u003e\u003cp\u003eHypocalcemia has been identified as a risk factor associated with increased mortality in patients with COVID-19, Ebola, Dengue fever and SFTS(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Previous studies indicated that the incidence of hypocalcemia in COVID-19 patients range from 59.3% to 76.6% and found that total calcium\u0026thinsp;\u0026le;\u0026thinsp;2.02 mmol/L or 8.38 mg/dL had increased risk of in-hospital mortality(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Several studies found that hypocalcemia was also associated with increased mortality in non-viral infectious diseases such as acute pulmonary thromboembolism, heart failure and chronic kidney disease (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The mechanisms underlying this may involve pro-inflammatory cytokine release, end-organ resistance to parathyroid hormone, vitamin D deficiency or insufficiency(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). To the best of our knowledge, there have been very few studies investigating serum calcium levels and the risk of death in SFTS patients(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, these two studies only investigated the impact of serum calcium on prognosis without considering the influence of albumin on serum calcium levels. Moreover, they did not provide the optimal critical value of serum calcium for estimating the disease severity or data on the dynamic changes in serum calcium levels during hospitalization.\u003c/p\u003e\u003cp\u003eOur study aimed to investigate the prevalence of hypocalcemia in SFTS patients upon hospital admission, evaluate the association between serum calcium levels and clinical outcomes, analyze dynamic changes in serum calcium levels during hospitalization, and determine the optimal critical threshold of serum calcium for assessing disease severity. These findings may facilitate early identification of high-risk patients and guide timely clinical interventions to improve prognosis.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients and Data Collection\u003c/h2\u003e\u003cp\u003eA total of 816 laboratory-confirmed SFTS patients admitted to the Department of Infectious Diseases at Wuhan Union Hospital from April 2017 to June 2024 were retrospectively analyzed. Laboratory confirmation of SFTS required meeting one or more of the following criteria: (a) detection of SFTSV RNA in the patient\u0026rsquo;s serum; (b) detection of IgM antibodies against SFTSV or a four-fold increase in serum IgG antibodies during the convalescent phase; or (c) detection of the SFTSV genome via next-generation sequencing. After excluding 7 patients with missing serum calcium records, 809 patients were ultimately included in the study. Patients were stratified into three groups based on serum calcium levels: G1 \u0026lt;7.0 mg/dL (n\u0026thinsp;=\u0026thinsp;59), 7.0\u0026thinsp;\u0026le;\u0026thinsp;G2\u0026lt;8.12 (n\u0026thinsp;=\u0026thinsp;529), G3\u0026thinsp;\u0026ge;\u0026thinsp;8.12 (n\u0026thinsp;=\u0026thinsp;221) (see S1 Fig). Two trained physicians retrospectively collected data on demographics, underlying diseases, clinical characteristics, laboratory findings, comorbidities, and overall prognosis from medical records.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were conducted using R (version 4.4.0; R Foundation for Statistical Computing, Vienna, Austria). Continuous variables were presented as median (1st Quartile, 3st Quartile) or mean (\u0026plusmn;\u0026thinsp;standard deviation). Significant differences between two groups were assessed using the Student\u0026rsquo;s t-test or the nonparametric two-tailed Mann-Whitney U test. Categorical variables were expressed as percentages (%), and significant differences between two groups were analyzed using the chi-square test or Fisher\u0026rsquo;s exact test. Differences among multiple groups were determined using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Multivariate logistic regression analyses were used to identify independent risk factors for mortality and corrected calcium levels. Survival analysis, stratified by corrected calcium levels across the four groups, was performed using Kaplan-Meier (KM) curves with the log-rank test. Restricted cubic splines (RCS) were used to further investigate the association between calcium levels and SFTS mortality. The dynamic changes in serum calcium levels, tracked from admission to discharge or death, were visualized using locally weighted scatterplot smoothing (LOESS). The relationships between serum calcium levels and viral load, creatine kinase, and APTT, IL-6, IL-10, CD4\u003csup\u003e+\u003c/sup\u003eT cell at hospital admission were assessed using linear regression models to evaluate the strength and significance of these associations. All statistical tests were two-tailed, and a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eBaseline characteristics of the study population.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, a total of 809 patients were enrolled in this study, of whom 96 (11.87%) died during hospitalization. The median age of the study population was 63 years (interquartile range [IQR]: 55\u0026ndash;70), with 342 (42.27%) male participants. Major comorbidities included hypertension in 191 patients (23.61%), diabetes mellitus in 93 (11.50%), chronic obstructive pulmonary disease (COPD) in 33 (4.08%), and chronic hepatitis B (CHB) in 83 (10.26%). Neurological and hemorrhagic manifestations occurred in 26.70% and 12.48% of cases, respectively. The median hospital stay was 9 days (interquartile range [IQR]: 7\u0026ndash;12), with 21 cases (2.60%) requiring intensive care unit (ICU) transfer. Patients were stratified into survival (n\u0026thinsp;=\u0026thinsp;713) and non-survival (n\u0026thinsp;=\u0026thinsp;96) groups based on clinical outcomes. Comparative analysis revealed significant between-group differences, non-survivors were older than survivors (median age 70 [IQR 62\u0026ndash;75] vs. 62 [IQR 54\u0026ndash;69] years; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and had higher hypertension prevalence (40.61% [39/96] vs. 21.32% [152/713]; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No intergroup differences were detected in sex distribution (P\u0026thinsp;=\u0026thinsp;0.472), diabetes mellitus (P\u0026thinsp;=\u0026thinsp;0.356), chronic obstructive pulmonary disease (COPD; P\u0026thinsp;=\u0026thinsp;0.621), or chronic hepatitis B (CHB; P\u0026thinsp;=\u0026thinsp;0.843) prevalence. Notably, the non-survival group demonstrated significantly higher frequencies of neurological manifestations (67.71% vs. 21.18%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hemorrhagic manifestations (20.83% vs. 11.36%, P\u0026thinsp;=\u0026thinsp;0.008), and ICU transfer (9.38% vs. 1.68%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics and Laboratory Parameters in Patients With SFTS\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;809)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSurvivors (n\u0026thinsp;=\u0026thinsp;713)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNon-survivors (n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e63.00 (55.00, 70.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e62.00 (54.00, 69.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70.00 (63.00, 73.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, male (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e342 (42.27%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e301 (42.22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41 (42.71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.927\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e191 (23.61%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e152 (21.32%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e39 (40.61%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e93 (11.50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e81 (11.36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12 (12.50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.7424\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33 (4.08%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (3.93%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (5.21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.7482\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e83 (10.26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78 (10.94%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (5.21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0823\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e216 (26.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e151 (21.18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e65 (67.71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhagic signs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e101 (12.48%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e81 (11.36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20 (20.83%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0084\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory parameters\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.80 (7.48, 8.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.84 (7.52, 8.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.48 (7.00, 7.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e31.74\u0026thinsp;\u0026plusmn;\u0026thinsp;4.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31.91\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.41\u0026thinsp;\u0026plusmn;\u0026thinsp;4.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCorrected Calcium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.45 (8.17, 8.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.48 (8.20, 8.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.22 (7.81, 8.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViral load (Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.07(2.06, 4.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.91(2.00, 3.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.07 (4.11, 5.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.85 (1.76, 4.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.90 (1.78, 4.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.39 (1.68, 4.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.1302\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.20 (3.82, 4.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.20 (3.82, 4.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.22 (3.89, 4.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.6886\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e126.00(115.00, 139.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e125.00(115.00, 139.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e127.50 (116.00, 139.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4417\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.00 (34.00, 64.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51.00 (36.00, 66.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e35.50 (24.00, 49.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.69 (0.44, 1.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.70 (0.45, 1.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.57 (0.33, 0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.16 (0.08, 0.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.18 (0.08, 0.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.095 (0.058, 0.173)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.64 (0.95, 3.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.69 (0.92, 3.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.51 (1.08, 2.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.907\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e80.00(48.00, 142.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e77.00 (47.00, 129.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e118.50 (62.75, 195.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e185.00 (101.00, 362.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e174.0000 (95.00, 321.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e409.00 (222.25, 690.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTbil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.40 (7.00, 12.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.40 (6.90, 12.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.95 (7.18, 13.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.2994\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57.40 (53.30, 61.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57.50 (53.40, 61.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e56.95 (52.15, 60.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobulin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25.30 (22.80, 28.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.20 (22.60, 28.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e25.8500 (23.98, 29.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0168\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e70.00 (58.00, 85.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e68.60 (57.20, 82.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e90.2500 (70.10, 148.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.82 (3.45, 6.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.6200 (3.34, 6.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.56 (5.53, 11.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.88 (2.69, 3.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.86 (2.67, 3.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.13 (2.90, 3.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.70 (2.36, 3.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.67 (2.33, 3.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.08(2.63, 3.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTnI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e106.00 (44.10, 555.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e97.70 (40.30, 447.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e227.10 (92.23, 688.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKMB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.70 (1.90, 7.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.50 (1.80, 6.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.28 (3.28, 9.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSodium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e135.60 (133.00, 138.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e135.60 (133.10, 138.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e135.40 (132.25, 138.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4116\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.63 (3.30, 3.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.60 (3.29, 3.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.96 (3.53, 4.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.78 (0.68, 0.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.78 (0.69, 0.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.75 (0.68, 0.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.1325\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphorus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.90 (0.76, 1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.90 (0.76, 1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.95 (0.79, 1.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0206\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.20 (42.70, 59.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48.90 (41.70, 57.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e67.60 (55.30, 83.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eD-dimer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.90 (1.40, 5.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.57 (1.31, 4.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.01 (2.98, 10.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFIB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.49 (2.05, 2.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.50 (2.08, 3.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.41 (1.97, 2.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.03 (0.94, 1.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.02 (0.94, 1.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.09 (1.00, 1.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13.20 (12.40, 14.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13.10 (12.30, 14.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.70 (13.00, 15.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24.40 (20.40, 31.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.70 (20.10, 29.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40.20 (26.66, 62.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital stay\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.00 (7.00, 12.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.00 (8.00, 12.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.00 (2.00, 4.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICU transfer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (2.60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (1.68%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (9.38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations and normal range: SFTS, severe fever with thrombocytopenia syndrome; COPD, chronic obstructive pulmonary disease; CHB, chronic hepatitis B; ICU, intensive care unit; Calcium, 8.12-10.16mg/dL(2.03-2.54mmol/L); Albumin, 35-55g/L; Corrected calcium, 8.5\u0026ndash;10.2 mg/dL; Viral load, \u0026lt; 100TCID50/ml; WBC, white blood cell, 3.5\u0026ndash;9.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L; RBC, red blood cell, 3.8\u0026ndash;5.1\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L; Hb, hemoglobin, 115-150g/L; PLT, platelet,125\u0026ndash;350\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L; ALT, alanine aminotransferase, 5-35U/L; AST, aspartate aminotransferase, 8-40U/L; TBIL, total bilirubin, 5.1-19umol/L; TP, total protein, 64-83g/L; Globulin, 20-30g/L; Creatinine, 44-106umol/L; BUN, blood urea nitrogen, 2.9-8.2mmol/L; LDH, lactate dehydrogenase, 109-245U/L; CK, Creatine kinase, 38-174U/L; cTnI, cardiac troponin I, \u0026lt; 26.2ng/L; CKMB, Creatine Kinase MB, \u0026lt; 6.6ng/L; Sodium, 136-145mmol/L; Potassium, 3.5-5.2mmol/L, Magnesium, 0.7-1.1mmol/L; Phosphorus, 0.96-1.62mmol/L; APTT, activated partial thromboplastin time, 28-43.5s; D-dimer, \u0026lt;0.5ug/mL FEU; FEU, fibrinogen equivalent unit; FIB, fibrinogen, 2.0-4.0g/L; INR, international normalized ratio, 0.8\u0026ndash;1.2; PT, prothrombin time, 11-14.2s; TT, thrombin time, 14-21s.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eLaboratory findings revealed that non-survivors had significantly lower levels of serum albumin, calcium, corrected calcium, platelet count (PLT), lymphocyte count, and monocyte count compared to survivors (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, non-survivors showed significantly higher levels of viral load; liver function biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST]); renal function biomarkers (creatinine, blood urea nitrogen [BUN]); myocardial injury-related biomarkers (creatine kinase, lactate dehydrogenase [LDH], cTnI, creatine kinase-MB [CK-MB]); coagulation parameters (APTT, D-dimer, international normalized ratio [INR], prothrombin time [PT], thrombin time [TT]); and potassium (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eAmong the 809 patients with SFTS, lymphocyte subsets (sTable1) were analyzed in 78 cases (9.6%; survival group: n\u0026thinsp;=\u0026thinsp;71, non-survival group: n\u0026thinsp;=\u0026thinsp;7), and cytokine profiles (sTable2) were assessed in 239 cases (29.5%; survival group: n\u0026thinsp;=\u0026thinsp;214, non-survival group: n\u0026thinsp;=\u0026thinsp;25). Comparative analysis revealed significant immunological differences between the two groups. The survival group exhibited higher absolute counts of B lymphocytes (B cells), CD3\u0026thinsp;+\u0026thinsp;T cells, CD4\u0026thinsp;+\u0026thinsp;T cells, and CD8\u0026thinsp;+\u0026thinsp;T cells compared to the non-survival group. In contrast, natural killer (NK) cell counts were lower in survivors. The most pronounced differences were observed in CD3\u0026thinsp;+\u0026thinsp;T cells, CD4\u0026thinsp;+\u0026thinsp;T cells, and CD8\u0026thinsp;+\u0026thinsp;T cell populations (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for all). Non-survivors demonstrated significantly elevated levels of pro-inflammatory and anti-inflammatory cytokines, including IFN-γ, IL-10, IL-4, and IL-6. Conversely, TNF-α and IL-2 levels were lower in non-survivors. The most marked differences were observed in IFN-γ, IL-10, and IL-6 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cb\u003eThe association between serum calcium and clinical outcomes.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUnivariate and multivariate logistic regression analysis on the risk factors associated with mortality of SFTS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) demonstrated that lower serum calcium as an independent predictor for in-hospital mortality, along with older age, neurological symptoms, higher viral loads, lower albumin and elevated creatinine. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the baseline characteristics of all patients stratified by calcium levels. The cohorts were divided into three groups based on baseline corrected calcium levels: G1 \u0026lt;7.0 mg/dL, 7.0 mg/dL\u0026thinsp;\u0026le;\u0026thinsp;G2\u0026lt;8.12 mg/dL, G3\u0026thinsp;\u0026ge;\u0026thinsp;8.12 mg/dL, comprising 59, 529, and 221 patients, respectively. Patients with lower calcium levels were predominantly older, male and exhibited higher rates of neurological symptoms, hemorrhagic signs, ICU admission, and mortality. No significant intergroup differences were observed in comorbidities such as hypertension, diabetes, COPD, and CHB. Mortality, viral load, renal function biomarkers (creatinine and blood urea nitrogen), and coagulation parameters (APTT, D-dimer, fibrinogen [FIB], INR, and PT) were negatively correlated with calcium levels (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In contrast, lymphocyte and monocyte counts were positively correlated with calcium levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariate logistic regression analysis on the risk factors associated with mortality of SFTS\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMultivariate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.23 (0.15\u0026thinsp;~\u0026thinsp;0.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.26 (0.10\u0026thinsp;~\u0026thinsp;0.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.09 (1.06\u0026thinsp;~\u0026thinsp;1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.13 (1.06\u0026thinsp;~\u0026thinsp;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.80 (4.91\u0026thinsp;~\u0026thinsp;12.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.91 (3.21\u0026thinsp;~\u0026thinsp;19.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViral load (Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.50 (2.73\u0026thinsp;~\u0026thinsp;4.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.24 (1.44\u0026thinsp;~\u0026thinsp;3.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.93 (0.88\u0026thinsp;~\u0026thinsp;0.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.18 (1.03\u0026thinsp;~\u0026thinsp;1.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02 (1.01\u0026thinsp;~\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.02 (1.01\u0026thinsp;~\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06 (1.05\u0026thinsp;~\u0026thinsp;1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.04 (1.01\u0026thinsp;~\u0026thinsp;1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhagic signs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.05 (1.19\u0026thinsp;~\u0026thinsp;3.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.58 (0.14\u0026thinsp;~\u0026thinsp;2.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.444\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.53 (1.62\u0026thinsp;~\u0026thinsp;3.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.33 (0.49\u0026thinsp;~\u0026thinsp;3.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.571\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.97 (0.95\u0026thinsp;~\u0026thinsp;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.97 (0.95\u0026thinsp;~\u0026thinsp;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.22 (0.08\u0026thinsp;~\u0026thinsp;0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.61 (0.15\u0026thinsp;~\u0026thinsp;2.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.01\u0026thinsp;~\u0026thinsp;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00 (1.00\u0026thinsp;~\u0026thinsp;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.14 (13.48\u0026thinsp;~\u0026thinsp;71.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.98 (0.11\u0026thinsp;~\u0026thinsp;34.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.639\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.56 (1.71\u0026thinsp;~\u0026thinsp;3.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.45 (0.12\u0026thinsp;~\u0026thinsp;1.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.233\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTnI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.01\u0026thinsp;~\u0026thinsp;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00 (1.00\u0026thinsp;~\u0026thinsp;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK-MB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.05 (1.03\u0026thinsp;~\u0026thinsp;1.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.96\u0026thinsp;~\u0026thinsp;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.693\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics and outcomes of SFTS patients categorized by calcium on admission\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003ebaseline Calcium\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eG1 \u0026lt;7.0 (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0\u0026thinsp;\u0026le;\u0026thinsp;G2\u0026lt;8.12 (n\u0026thinsp;=\u0026thinsp;529)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eG3\u0026thinsp;\u0026ge;\u0026thinsp;8.12 (n\u0026thinsp;=\u0026thinsp;221)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, M (Q₁, Q₃)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66.00 (57.00,71.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e63.00 (56.00,70.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e62.00 (54.00,67.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e38 (64.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e216 (40.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e88 (39.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological symptoms, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24 (40.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e151 (28.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41 (18.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhagic signs, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (23.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e62 (11.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e25 (11.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (27.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e125 (23.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e50 (22.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (6.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e67 (12.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22 (9.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (6.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20 (3.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (4.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.543\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHB, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (8.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55 (10.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23 (10.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.896\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory parameters\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViral load (Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.94 (3.11,5.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.16 (2.26,4.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.51 (1.44,3.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.71 (1.88,4.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.81 (1.70,4.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.95 (1.88,4.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.464\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.26 (3.82,4.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.16 (3.82,4.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.27 (3.88,4.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.166\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e127.00 (113.00,142.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e125.00 (115.00,139.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e127.00 (116.00,139.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.539\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40.00 (27.00,53.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48.00 (34.00,61.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e57.00 (39.00,79.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.63 (0.41,1.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.64 (0.41,1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.90 (0.50,1.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.11 (0.06,0.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.15 (0.08,0.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.22 (0.10,0.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.97 (1.23,2.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.66 (0.93,3.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.59 (0.92,2.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.647\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e117.00 (68.00,180.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83.00 (49.00,151.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e67.00 (45.00,113.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e333.00 (169.00,703.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e205.00 (109.00,388.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e138.00 (79.00,231.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTbil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.50 (7.95,12.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.00 (6.80,12.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.30 (7.80,13.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e54.40 (50.70,58.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e56.25 (52.80,60.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e60.60 (56.70,64.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28.60 (25.50,31.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31.10 (28.30,33.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.20 (30.90,37.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobulin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25.20 (22.40,28.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.10 (22.50,27.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26.05 (23.48,29.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e88.85 (68.85,127.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e68.45 (57.90,85.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e65.50 (55.95,80.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.01 (4.49,9.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.81 (3.45,6.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.56 (3.29,6.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.09 (2.89,3.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.89 (2.72,3.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.76 (2.58,2.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.12 (2.71,3.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.71 (2.40,3.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.55 (2.16,2.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTnI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e107.70 (68.05,419.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e85.30 (41.50,227.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e59.30 (21.80,125.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK-MB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.20 (2.20,12.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.25 (1.60,6.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.80 (1.20,5.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.72 (6.56,6.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.64 (7.44,7.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.36 (8.20,8.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSodium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e135.40 (131.70,137.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e135.20 (132.60,137.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e137.10 (134.20,140.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.78 (3.28,4.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.60 (3.29,3.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.67 (3.37,3.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.71 (0.65,0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.76 (0.67,0.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.80 (0.73,0.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphorus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.77,1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.87 (0.73,1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.93 (0.78,1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e63.50 (50.95,81.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51.10 (44.60,60.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43.35 (37.88,51.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eD-dimer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.17 (2.92,8.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.71 (1.45,5.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.56 (0.91,3.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFIB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.20 (1.71,2.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.47 (2.05,2.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.73 (2.22,3.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.11 (1.03,1.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.02 (0.94,1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00 (0.93,1.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14.10 (13.20,15.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13.10 (12.40,14.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.80 (12.20,13.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.40 (22.70,59.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24.60 (20.60,31.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.80 (18.83,26.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatality, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (37.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e63 (11.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (4.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospitalstay\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.00 (3.50,13.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.00 (7.00,12.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.00 (6.00,11.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICUtransfer, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (8.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (2.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (0.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eG1, comprising 59 cases, was associated with significantly higher mortality (37.29%) and an increased likelihood of ICU transfer (8.47%). This group also exhibited the highest levels of viral load; liver function biomarkers (ALT, AST, and total bilirubin [Tbil]); renal function biomarkers (creatinine and BUN); myocardial injury-related biomarkers (LDH, creatine kinase, and CK-MB); and coagulation function biomarkers (APTT, D-dimer, INR, PT, and TT) (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the lowest level of PLT, lymphocyte, monocyte, albumin and magnesium (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Patients in G3 exhibited the lowest mortality rate (4.98%) and ICU transfer rate (0.9%), had the mildest clinical conditions, characterized by the highest lymphocyte and monocyte counts, the lowest levels of viral load, the lowest levels of renal function biomarkers (creatinine and BUN) and coagulation function biomarkers (APTT, D-dimer, INR, PT, and TT) (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eKaplan-Meier survival analysis results are presented in S1 Fig, demonstrating significant divergence in survival probabilities among the three groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Hypocalcemia was significantly associated with an increased risk of 28-day all-cause mortality. The highest survival rate was observed in G3, while the lowest survival rate was found in G1.\u003c/p\u003e\u003cp\u003eRCS analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) revealed a significant L-shaped association between serum calcium levels and in-hospital mortality. The mortality risk sharply decreased with increasing calcium levels until reaching an inflection point at 7.5628 mg/dL upon admission (p for nonlinearity\u0026thinsp;=\u0026thinsp;0.733). Below this threshold, each unit decrease in calcium was associated with a marked elevation in mortality risk. However, above the cut-off value of 7.5628 mg/dL, the mortality risk plateaued and no longer demonstrated significant variation with further increases in corrected calcium levels. A similar relationship was observed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, where the mortality risk sharply decreased with increasing corrected calcium levels until reaching an inflection point at 8.4532 mg/dL upon admission (p for nonlinearity\u0026thinsp;=\u0026thinsp;0.725).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDynamic change of serum calcium during hospitalization.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe conducted a kinetic analysis of calcium, albumin, and corrected calcium levels, tracking their changes from day 1 to day 28 or or until discharge after admission (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The trajectories of calcium, albumin, and corrected calcium levels from day 1 to day 12 or until discharge after admission are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. At each time point, the calcium and albumin levels in the survival group were consistently higher than those in the non-survival group. Except for the 6-8th days after admission, the corrected calcium levels in the survival group were consistently higher than those in the non-survival group at all other time points. In the survival group, serum calcium showed an upward trend and reached the normal range by the 6th day after admission. While it gradually increased, reaching its peak on the 6th day and then gradually decreased in the non-survival group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ePotential factors associated with low serum calcium.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUnivariate and multivariate logistic regression analyses of factors associated with hypocalcemia are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. To further investigate the characteristics associated with hypocalcemia in SFTS patients, we stratified the cohort by admission serum calcium levels into a hypocalcemia group (calcium\u0026thinsp;\u0026lt;\u0026thinsp;8.12 mg/dL) and a normocalcemia group (calcium\u0026thinsp;\u0026ge;\u0026thinsp;8.12 mg/dL). Patients with hypocalcemia were significantly older and exhibited higher viral loads, elevated levels of AST, creatinine, BUN, LDH, CK, CK-MB, and prolonged APTT. Conversely, the hypocalcemia group demonstrated significantly lower PLT, lymphocyte and monocyte counts, TP, albumin, magnesium, and sodium levels. Multivariate logistic regression analysis identified several independent factors significantly associated with hypocalcemia at admission. These included lower albumin levels (OR\u0026thinsp;=\u0026thinsp;0.80, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), lower globulin levels (OR\u0026thinsp;=\u0026thinsp;0.93, p\u0026thinsp;=\u0026thinsp;0.002), lower sodium levels (OR\u0026thinsp;=\u0026thinsp;0.93, p\u0026thinsp;=\u0026thinsp;0.002), and lower monocyte counts (OR\u0026thinsp;=\u0026thinsp;0.48, p\u0026thinsp;=\u0026thinsp;0.05). These findings indicate that hypoalbuminemia, hypoglobulinemia, hyponatremia, and monocytopenia represent independent risk factors for hypocalcemia in SFTS patients. Linear regression analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) revealed statistically significant inverse associations between serum calcium levels and viral loads (R\u0026sup2; = 0.0695, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), CK (R\u0026sup2; = 0.0875, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), APTT (R\u0026sup2; = 0.1097, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), IL-6 (R\u0026sup2; = 0.0172, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0432), IL-10 (R\u0026sup2; = 0.0323, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0053). These findings suggest that hypocalcemia was independently associated with higher viral load, myocardial injury (indicated by CK elevation), coagulation dysfunction (indicated by prolonged APTT), and cytokine storm (reflected by elevated IL-6 and IL-10 levels) in patients with SFTS.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariate logistic regression analysis of risk factors associated with hypocalcemia\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMultivariate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR (95%CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.82 (0.79\u0026thinsp;~\u0026thinsp;0.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.80 (0.76\u0026thinsp;~\u0026thinsp;0.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobulin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.95 (0.92\u0026thinsp;~\u0026thinsp;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.93 (0.89\u0026thinsp;~\u0026thinsp;0.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSodium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.90 (0.87\u0026thinsp;~\u0026thinsp;0.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.93 (0.88\u0026thinsp;~\u0026thinsp;0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.42 (0.26\u0026thinsp;~\u0026thinsp;0.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.48 (0.23\u0026thinsp;~\u0026thinsp;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.050\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02 (1.01\u0026thinsp;~\u0026thinsp;1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00 (0.98\u0026thinsp;~\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.810\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViral load(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.34 (1.20\u0026thinsp;~\u0026thinsp;1.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.12 (0.95\u0026thinsp;~\u0026thinsp;1.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.177\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.99\u0026thinsp;~\u0026thinsp;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.01 (1.00\u0026thinsp;~\u0026thinsp;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.139\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65 (0.52\u0026thinsp;~\u0026thinsp;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.89 (0.60\u0026thinsp;~\u0026thinsp;1.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.568\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.01\u0026thinsp;~\u0026thinsp;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00 (1.00\u0026thinsp;~\u0026thinsp;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.513\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.01\u0026thinsp;~\u0026thinsp;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.01 (1.00\u0026thinsp;~\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.121\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.07 (1.01\u0026thinsp;~\u0026thinsp;1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.98 (0.88\u0026thinsp;~\u0026thinsp;1.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.715\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK(Log10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.40 (1.76\u0026thinsp;~\u0026thinsp;3.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.08 (0.71\u0026thinsp;~\u0026thinsp;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.719\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.10 (0.03\u0026thinsp;~\u0026thinsp;0.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.34 (0.08\u0026thinsp;~\u0026thinsp;1.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.137\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.04 (1.03\u0026thinsp;~\u0026thinsp;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.01 (0.99\u0026thinsp;~\u0026thinsp;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.514\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study explored the relationship between serum calcium levels, their dynamic changes, and in-hospital mortality in patients with SFTS. Our results demonstrate that hypocalcemia is prevalent among SFTS patients upon admission and is significantly associated with the development of neurological symptoms. Furthermore, serum calcium levels emerged as an independent predictor of mortality, alongside other well-established risk factors such as older age, neurological symptoms, higher viral loads, lower albumin, elevated creatinine, and prolonged APTT. These findings underscore the importance of monitoring and managing calcium levels in SFTS patients to improve clinical outcomes.\u003c/p\u003e\u003cp\u003eOur study enrolled 809 SFTS patients, with a mortality rate of 11.87%, consistent with previous reports that mortality in SFTS ranges from 10% to 30%(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Hypocalcemia was observed in 72.68% of patients upon admission, indicating its high prevalence in SFTS. This finding aligns with studies on COVID-19, SARS and Ebola viruses, which have also identified hypocalcemia as a common feature in critically ill patients.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Hypocalcemia was observed in 60\u0026ndash;75% of COVID-19 patients, 60% of SARS patients, and a similar proportion of Ebola virus disease patients(\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), which was similar with our study. Currently, there is very limited research on serum calcium in SFTS. Only one retrospective study from China found that serum calcium levels were an independent protective factor against in-hospital mortality in SFTS patients(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Our study found that calcium levels were strongly associated with the development of neurological symptoms and mortality, suggesting that hypocalcemia may play a pathogenic role in SFTS progression, likely due to its role in cellular signaling, muscle contraction, and coagulation(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). RCS analysis revealed a significant L-shaped association between serum calcium levels and in-hospital mortality, indicating that both severe hypocalcemia and hypercalcemia may be detrimental, but the risks are more pronounced at lower calcium levels, particularly when serum calcium \u0026lt;7.5628 mg/dL. Consistent with previous studies on acute myocardial infarction(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The dynamic analysis further supported this observation, showing that serum calcium levels in the survival group consistently increased and normalized by the 6th day after admission, whereas in the non-survival group, calcium levels peaked on the 6th day and then declined. Monitoring and maintaining adequate calcium levels in all hospitalized patients with SFTS is recommended.\u003c/p\u003e\u003cp\u003eHypocalcemia is also seen in several viral infections, such as Ebola virus, dengue fever, and COVID-19(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). The potential causes of hypocalcemia in SFTS patients may include the following(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e): (a) Most SFTS patients experience severe anorexia, nausea, vomiting, and diarrhea, leading to reduced calcium intake and increased excretion; (b) Calcium is primarily bound to plasma albumin, and decreased serum albumin levels can contribute to hypocalcemia; (c) The SFTS virus may directly damage cells, disrupting calcium ion metabolism; (d) Excessive immune and inflammatory responses may cause calcium metabolism disorders, resulting in hypocalcemia; (e) The virus may impair kidney function, affecting calcium reabsorption and vitamin D activation; (f) Medications used in treatment, such as antivirals or antibiotics, may interfere with calcium metabolism; (g) Viral infection may impact the secretion of parathyroid hormone and vitamin D, leading to abnormal calcium metabolism. The dynamic analysis in our study revealed that serum calcium and albumin levels in non-survivors were consistently lower than those in the survivor group. Serum calcium levels were negatively correlated with viral load and renal function markers (creatinine and BUN) and positively correlated with lymphocyte and monocyte counts. Our findings support the above hypothesis. Thus, early correction of hypocalcemia and hypoproteinemia has been suggested to improve survival, as dynamic studies show that normalized calcium and albumin levels correlate with better outcomes.\u003c/p\u003e\u003cp\u003eThe linear correlation analysis revealed that hypercalcemia was associated with higher viral load, myocardial injury, coagulation dysfunction, and cytokine storm, providing insights into the potential mechanisms underlying the poor outcomes associated with hypocalcemia. Calcium is essential for maintaining cellular homeostasis, and its deficiency may exacerbate viral replication, impair cardiac function, potentially contributing to neurological symptoms such as seizures or altered mental status, and disrupt coagulation pathways(\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). These findings align with the known pathophysiology of SFTS, which involves widespread endothelial damage, immune dysregulation, and multi-organ dysfunction(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Hypocalcemia may thus serve as both a marker of disease severity and a contributor to the pathogenic cascade in SFTS. Additionally, the interplay between calcium levels and other biomarkers, such as viral load, cardiac troponin I, APTT and IL-6 warrants further investigation to better understand the complex pathophysiology of SFTS.\u003c/p\u003e\u003cp\u003eOur study found that over half of SFTS patients exhibited hypocalcemia upon admission, and lower serum calcium levels were associated with a significantly increased mortality risk. Specifically, when serum calcium levels fell below 7.56 mg/dL or corrected calcium levels dropped below 8.45 mg/dL, mortality rates rose markedly. Appropriate management of this imbalance will be useful in the treatment of SFTS patients. A pilot study conducted in Mexico involving a cohort of dengue-infected patients demonstrated that oral supplementation with calcium carbonate (CaCO₃) combined with vitamin D₃ significantly enhanced platelet count, improved clinical outcomes, and reduced the duration of disease(\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). However, in the context of sepsis management, calcium supplementation has been shown to lack clinical efficacy and may pose potential risks to patient outcomes(\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). For SFTS, there is currently no available data regarding the effects of calcium supplementation in patients with hypocalcemia. Recent studies reported that SFTSV infection induces progressive Ca2\u0026thinsp;+\u0026thinsp;influx, which can be effectively inhibited by benidipine hydrochloride administration. This treatment not only enhances viral clearance and improves clinical outcomes but also leads to a significant reduction in case fatality rates(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Research findings on COVID-19 further corroborated this observation, showing that therapeutic intervention with amlodipine besylate, a calcium channel blocker, led to a decreased case fatality rate among patients(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Therefore, future research should prioritize elucidating the pathophysiological mechanisms underlying the association between hypocalcemia and adverse clinical outcomes in SFTS. Well-designed prospective studies are warranted to evaluate whether early therapeutic interventions, including calcium supplementation or calcium channel blockers (CCBs), can improve survival rates and reduce disease-related complications in this patient population.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, it is a single-center study, and the findings may not be generalizable to other populations, future multicenter studies are necessary to validate our findings. Second, while the study demonstrates associations between calcium levels and outcomes, it does not establish causality. Mechanistic studies are needed to elucidate the underlying pathways linking hypocalcemia to virus replication, myocardial injury, coagulation dysfunction, and cytokine storm in SFTS. Finally, the study did not evaluate the impact of calcium supplementation or other interventions on clinical outcomes, which should be explored in future trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical study was reviewed and successfully approved by the institutional review board of Tongji Medical College (2023-S093). \u0026nbsp;The study was conducted in accordance with the principles of the Helsinki declaration of 1975, as revised in 1983.The requirement for getting written informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data\u003c/strong\u003e: The original data generated in this analysis are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests\u003c/strong\u003e: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe work was supported by grants from the National Key R\u0026amp;D Program of China (2022YFC2305100) and the National Science and Technology Major Project of China (grant 92169121).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eHuan Wang performed the study, data collection, and wrote the article. Sisi Fang contributed to data analysis. Hua Wang contributed to data collection. Xin Zheng was responsible for designing the study, revising the article, and securing funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCasel MA, Park SJ, Choi YK. Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy. Experimental \u0026amp; Molecular Medicine. 2021;53(5):713-22. doi: 10.1038/s12276-021-00610-1.\u003c/li\u003e\n\u003cli\u003eYu X-J, Liang M-F, Zhang S-Y, Liu Y, Li J-D, Sun Y-L, et al. Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China. New England Journal of Medicine. 2011;364(16):1523-32. doi: 10.1056/NEJMoa1010095.\u003c/li\u003e\n\u003cli\u003eKim YR, Yun Y, Bae SG, Park D, Kim S, Lee JM, et al. Severe Fever with Thrombocytopenia Syndrome Virus Infection, South Korea, 2010. Emerging Infectious Diseases. 2018;24(11):2103-5. doi: 10.3201/eid2411.170756.\u003c/li\u003e\n\u003cli\u003eTakahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, et al. The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan. The Journal of Infectious Diseases. 2014;209(6):816-27. doi: 10.1093/infdis/jit603.\u003c/li\u003e\n\u003cli\u003eMcMullan LK, Folk SM, Kelly AJ, MacNeil A, Goldsmith CS, Metcalfe MG, et al. A new phlebovirus associated with severe febrile illness in Missouri. The New England journal of medicine. 2012;367(9):834-41. Epub 2012/08/31. doi: 10.1056/NEJMoa1203378. PubMed PMID: 22931317.\u003c/li\u003e\n\u003cli\u003eWin AM, Nguyen YTH, Kim Y, Ha NY, Kang JG, Kim H, et al. Genotypic Heterogeneity of Orientia tsutsugamushi in Scrub Typhus Patients and Thrombocytopenia Syndrome Co-infection, Myanmar. Emerg Infect Dis. 2020;26(8):1878-81. Epub 2020/07/21. doi: 10.3201/eid2608.200135. PubMed PMID: 32687023; PubMed Central PMCID: PMCPMC7392420.\u003c/li\u003e\n\u003cli\u003eLin T-L, Ou S-C, Maeda K, Shimoda H, Chan JP-W, Tu W-C, et al. The first discovery of severe fever with thrombocytopenia syndrome virus in Taiwan. Emerging Microbes \u0026amp; Infections. 2020;9(1):148-51. doi: 10.1080/22221751.2019.1710436.\u003c/li\u003e\n\u003cli\u003eLi H, Lu Q-B, Xing B, Zhang S-F, Liu K, Du J, et al. Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011\u0026ndash;17: a prospective observational study. The Lancet Infectious Diseases. 2018;18(10):1127-37. doi: 10.1016/s1473-3099(18)30293-7.\u003c/li\u003e\n\u003cli\u003eSchoch CL, Ciufo S, Domrachev M, Hotton CL, Kannan S, Khovanskaya R, et al. NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database. 2020;2020. doi: 10.1093/database/baaa062.\u003c/li\u003e\n\u003cli\u003eLi H, Jiang X-M, Cui N, Yuan C, Zhang S-F, Lu Q-B, et al. Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome. Signal Transduction and Targeted Therapy. 2021;6(1). doi: 10.1038/s41392-021-00541-3.\u003c/li\u003e\n\u003cli\u003eLi H, Zhang L-K, Li S-F, Zhang S-F, Wan W-W, Zhang Y-L, et al. Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality. Cell Research. 2019;29(9):739-53. doi: 10.1038/s41422-019-0214-z.\u003c/li\u003e\n\u003cli\u003eStraus MR, Tang T, Lai AL, Flegel A, Bidon M, Freed JH, et al. Ca 2+ Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity. Journal of Virology. 2020;94(13). doi: 10.1128/jvi.00426-20.\u003c/li\u003e\n\u003cli\u003eBerlansky S, Sallinger M, Grabmayr H, Humer C, Bernhard A, Fahrner M, et al. Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies. Cells. 2022;11(2). doi: 10.3390/cells11020253.\u003c/li\u003e\n\u003cli\u003eNathan L, Lai AL, Millet JK, Straus MR, Freed JH, Whittaker GR, et al. Calcium Ions Directly Interact with the Ebola Virus Fusion Peptide To Promote Structure\u0026ndash;Function Changes That Enhance Infection. ACS Infectious Diseases. 2019;6(2):250-60. doi: 10.1021/acsinfecdis.9b00296.\u003c/li\u003e\n\u003cli\u003eShivanthan M, Rajapakse S. Dengue and Calcium. International Journal of Critical Illness and Injury Science. 2014;4(4). doi: 10.4103/2229-5151.147538.\u003c/li\u003e\n\u003cli\u003eKong F, Zhang F, Liu X, Qin S, Yang X, Kong D, et al. Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target. Cell Communication and Signaling. 2021;19(1). doi: 10.1186/s12964-021-00762-7.\u003c/li\u003e\n\u003cli\u003eMinasi A, Andreadi A, Maiorino A, Giudice L, De Taddeo S, D\u0026rsquo;Ippolito I, et al. Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19. Endocrine. 2022;79(3):577-86. doi: 10.1007/s12020-022-03239-w.\u003c/li\u003e\n\u003cli\u003evan Griensven J, Bah EI, Haba N, Delamou A, Camara BS, Olivier KJ-J, et al. Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015. Emerging Infectious Diseases. 2016;22(12). doi: 10.3201/eid2212.161136.\u003c/li\u003e\n\u003cli\u003eConstantine GR, Rajapakse S, Ranasinghe P, Parththipan B, Wijewickrama A, Jayawardana P. Hypocalcemia is associated with disease severity in patients with dengue. The Journal of Infection in Developing Countries. 2014;8(09):1205-9. doi: 10.3855/jidc.4974.\u003c/li\u003e\n\u003cli\u003eRaesi A, Saedi Dezaki E, Moosapour H, Saeidifard F, Habibi Z, Rahmani F, et al. Hypocalcemia in Covid-19: A Prognostic Marker for Severe Disease. Iranian journal of pathology. 2021;16(2):144-53. Epub 2021/05/04. doi: 10.30699/ijp.2020.130491.2442. PubMed PMID: 33936225; PubMed Central PMCID: PMCPMC8085287.\u003c/li\u003e\n\u003cli\u003eTorres B, Alcubilla P, Gonz\u0026aacute;lez-Cord\u0026oacute;n A, Inciarte A, Chumbita M, Cardozo C, et al. Impact of low serum calcium at hospital admission on SARS-CoV-2 infection outcome. International Journal of Infectious Diseases. 2021;104:164-8. doi: 10.1016/j.ijid.2020.11.207.\u003c/li\u003e\n\u003cli\u003eYang Yq, Wang X, Zhang Yj, Chen Yf, Wang L, Hu Xw, et al. Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism. Respirology. 2022;27(8):645-52. doi: 10.1111/resp.14243.\u003c/li\u003e\n\u003cli\u003eMiura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, et al. Association of Hypocalcemia With Mortality in Hospitalized Patients With Heart Failure and Chronic Kidney Disease. Journal of Cardiac Failure. 2015;21(8):621-7. doi: 10.1016/j.cardfail.2015.04.015.\u003c/li\u003e\n\u003cli\u003eHendy GN, Canaff L. Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis. Seminars in cell \u0026amp; developmental biology. 2016;49:37-43. Epub 2015/11/28. doi: 10.1016/j.semcdb.2015.11.006. PubMed PMID: 26612442.\u003c/li\u003e\n\u003cli\u003eCui H, Shen S, Chen L, Fan Z, Wen Q, Xing Y, et al. Global epidemiology of severe fever with thrombocytopenia syndrome virus in human and animals: a systematic review and meta-analysis. The Lancet Regional Health - Western Pacific. 2024;48:101133. doi: 10.1016/j.lanwpc.2024.101133.\u003c/li\u003e\n\u003cli\u003eOsman W, Al Fahdi F, Al Salmi I, Al Khalili H, Gokhale A, Khamis F. Serum Calcium and Vitamin D levels: Correlation with severity of COVID-19 in hospitalized patients in Royal Hospital, Oman. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;107:153-63. Epub 2021/04/24. doi: 10.1016/j.ijid.2021.04.050. PubMed PMID: 33892191; PubMed Central PMCID: PMCPMC8057687.\u003c/li\u003e\n\u003cli\u003eBooth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. Jama. 2003;289(21):2801-9. Epub 2003/05/08. doi: 10.1001/jama.289.21.JOC30885. PubMed PMID: 12734147.\u003c/li\u003e\n\u003cli\u003eUyeki TM, Mehta AK, Davey RT, Jr., Liddell AM, Wolf T, Vetter P, et al. Clinical Management of Ebola Virus Disease in the United States and Europe. The New England journal of medicine. 2016;374(7):636-46. Epub 2016/02/18. doi: 10.1056/NEJMoa1504874. PubMed PMID: 26886522; PubMed Central PMCID: PMCPMC4972324.\u003c/li\u003e\n\u003cli\u003eZang yan. Prognostic Value of Serum Calcium Levels in Severe Fever with Thrombocytopenia Syndrome. Advances in Clinical Medicine. 2024;14(05):133-41. doi: 10.12677/acm.2024.1451407.\u003c/li\u003e\n\u003cli\u003eSaurav S, Tanwar J, Ahuja K, Motiani RK. Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance. Molecular Aspects of Medicine. 2021;81. doi: 10.1016/j.mam.2021.101004.\u003c/li\u003e\n\u003cli\u003eSchmitz T, Thilo C, Linseisen J, Heier M, Peters A, Kuch B, et al. Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry. Scientific reports. 2021;11(1):2476. Epub 2021/01/30. doi: 10.1038/s41598-021-81929-7. PubMed PMID: 33510279; PubMed Central PMCID: PMCPMC7843683.\u003c/li\u003e\n\u003cli\u003eConstantine GR, Rajapakse S, Ranasinghe P, Parththipan B, Wijewickrama A, Jayawardana P. Hypocalcemia is associated with disease severity in patients with dengue. Journal of infection in developing countries. 2014;8(9):1205-9. Epub 2014/09/13. doi: 10.3855/jidc.4974. PubMed PMID: 25212087.\u003c/li\u003e\n\u003cli\u003eYang T, Huang H, Jiang L, Li J. Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (Review). International journal of molecular medicine. 2022;50(3). Epub 2022/07/21. doi: 10.3892/ijmm.2022.5174. PubMed PMID: 35856413; PubMed Central PMCID: PMCPMC9333902.\u003c/li\u003e\n\u003cli\u003eCappellini F, Brivio R, Casati M, Cavallero A, Contro E, Brambilla P. Low levels of total and ionized calcium in blood of COVID-19 patients. Clinical chemistry and laboratory medicine. 2020;58(9):e171-e3. Epub 2020/05/28. doi: 10.1515/cclm-2020-0611. PubMed PMID: 32459190.\u003c/li\u003e\n\u003cli\u003eSun JK, Zhang WH, Zou L, Liu Y, Li JJ, Kan XH, et al. Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019. Aging. 2020;12(12):11287-95. Epub 2020/06/27. doi: 10.18632/aging.103526. PubMed PMID: 32589164; PubMed Central PMCID: PMCPMC7343468.\u003c/li\u003e\n\u003cli\u003eAlbert SG, Scott Isbell T. Reconsideration of \u0026quot;Albumin corrected total calcium\u0026quot; Determinations: Potential errors in the Clinical management of disorders of calcium metabolism. Clinica chimica acta; international journal of clinical chemistry. 2023;544:117353. Epub 2023/04/20. doi: 10.1016/j.cca.2023.117353. PubMed PMID: 37076097.\u003c/li\u003e\n\u003cli\u003eUrata S, Yoshikawa R, Yasuda J. Calcium Influx Regulates the Replication of Several Negative-Strand RNA Viruses Including Severe Fever with Thrombocytopenia Syndrome Virus. J Virol. 2023;97(3):e0001523. Epub 2023/02/17. doi: 10.1128/jvi.00015-23. PubMed PMID: 36794941; PubMed Central PMCID: PMCPMC10062178.\u003c/li\u003e\n\u003cli\u003eNathan L, Lai AL, Millet JK, Straus MR, Freed JH, Whittaker GR, et al. Calcium Ions Directly Interact with the Ebola Virus Fusion Peptide To Promote Structure-Function Changes That Enhance Infection. ACS infectious diseases. 2020;6(2):250-60. Epub 2019/11/21. doi: 10.1021/acsinfecdis.9b00296. PubMed PMID: 31746195; PubMed Central PMCID: PMCPMC7040957.\u003c/li\u003e\n\u003cli\u003eFang D, Chen H. Association between serum calcium level and in-hospital mortality in patients with acute myocardial infarction: a retrospective cohort study. Scientific reports. 2022;12(1). doi: 10.1038/s41598-022-24566-y.\u003c/li\u003e\n\u003cli\u003eDeluque AL, Dimke H, Alexander RT. Biology of calcium homeostasis regulation in intestine and kidney. Nephrology Dialysis Transplantation. 2024;40(3):435-45. doi: 10.1093/ndt/gfae204 %J Nephrology Dialysis Transplantation.\u003c/li\u003e\n\u003cli\u003eSaijo M. Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2018;24(10):773-81. Epub 2018/08/14. doi: 10.1016/j.jiac.2018.07.009. PubMed PMID: 30098914.\u003c/li\u003e\n\u003cli\u003eCabrera-Cortina JI, S\u0026aacute;nchez-Vald\u0026eacute;z E, Cedas-DeLezama D, Ram\u0026iacute;rez-Gonz\u0026aacute;lez MD. Oral calcium administration attenuates thrombocytopenia in patients with dengue fever. Report of a pilot study. Proceedings of the Western Pharmacology Society. 2008;51:38-41. Epub 2008/01/01. PubMed PMID: 19544672.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez-Vald\u0026eacute;z E, Delgado-Aradillas M, Torres-Mart\u0026iacute;nez JA, Torres-Ben\u0026iacute;tez JM. Clinical response in patients with dengue fever to oral calcium plus vitamin D administration: study of 5 cases. Proceedings of the Western Pharmacology Society. 2009;52:14-7. Epub 2009/01/01. PubMed PMID: 22128411.\u003c/li\u003e\n\u003cli\u003eCollage RD, Howell GM, Zhang X, Stripay JL, Lee JS, Angus DC, et al. Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase kinase signaling. Crit Care Med. 2013;41(11):e352-60. Epub 2013/07/28. doi: 10.1097/CCM.0b013e31828cf436. PubMed PMID: 23887235; PubMed Central PMCID: PMCPMC3812408.\u003c/li\u003e\n\u003cli\u003eZhang LK, Sun Y, Zeng H, Wang Q, Jiang X, Shang WJ, et al. Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension. Cell discovery. 2020;6(1):96. Epub 2020/12/23. doi: 10.1038/s41421-020-00235-0. PubMed PMID: 33349633; PubMed Central PMCID: PMCPMC7752915.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"severe fever with thrombocytopenia syndrome, serum calcium, mortality","lastPublishedDoi":"10.21203/rs.3.rs-7866935/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7866935/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eSevere fever with thrombocytopenia syndrome (SFTS) is a viral infectious disease characterized by high mortality. Calcium dysregulation is implicated in viral replication and host immune response. We aimed to evaluate the association between serum calcium levels and in-hospital mortality in patients with SFTS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this retrospective cohort study, we enrolled 809 laboratory-confirmed SFTS patients admitted between April 2017 and June 2024. Hypocalcemia was defined as corrected calcium\u0026thinsp;\u0026lt;\u0026thinsp;8.12 mg/dL. Multivariate logistic regression, restricted cubic spline (RCS), and longitudinal analyses were employed to assess associations between serum calcium and mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe in-hospital mortality rate was 11.87% (96/809). Hypocalcemia was observed in 72.68% of patients (588/809) with SFTS upon admission. Multivariate logistic regression analysis revealed that lower serum calcium was an independent predictor of in-hospital mortality, alongside older age, neurological symptoms, higher viral loads, lower albumin levels, elevated creatinine, and prolonged activated partial thromboplastin time (APTT). Restricted cubic spline (RCS) analysis revealed a significant L-shaped association between serum calcium levels and in-hospital mortality, with a critical inflection point at 7.56 mg/dL. Dynamic analysis showed that serum calcium levels increased and normalized by day 6 in survivors but peaked and declined thereafter in non-survivors. Hypocalcemia was independently associated with hypoalbuminemia, hypoglobulinemia, hyponatremia, and monocytopenia. Furthermore, serum calcium levels were inversely correlated with viral load, creatine kinase, APTT, IL-6, and IL-10 (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eHypocalcemia is exceedingly common in SFTS patients and serves as a robust, independent prognostic marker for in-hospital mortality. Its association with high viral replication and host inflammatory response underscores its clinical significance. Serial monitoring of serum calcium could enhance risk stratification and guide management decisions in SFTS.\u003c/p\u003e","manuscriptTitle":"Association between serum calcium and in-hospital mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 08:32:51","doi":"10.21203/rs.3.rs-7866935/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-26T12:18:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T21:48:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309296180895500786543937394277986039814","date":"2026-01-13T08:29:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-25T07:47:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-16T14:18:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-16T14:06:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Virology Journal","date":"2025-10-15T10:14:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4343dc63-e616-4554-8632-fc2a75c44f21","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T17:38:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 08:32:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7866935","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7866935","identity":"rs-7866935","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}