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. 2025 May 17;7(3):183–191. doi: 10.1016/j.bsheal.2025.05.007

The holistic rehabilitation from acute severe fever with thrombocytopenia syndrome virus infection to 10 years after recovery: A cross-sectional study

Min Li a,b,1, Yalan Wang a,b,1, Peiwen Qiao a,b,1, Yaxin Guo a,b, Peipei Guo a,b,c, Tian Ma a,b, Shaobo Dong d, Jianbo Zhan e,⁎, Jun Liu f,2,⁎, Guizhen Wu a,b,g,2,⁎
PMCID: PMC12276564  PMID: 40693037

Highlights

  • Scientific questions The long-term health consequences of severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection remain poorly characterized, particularly regarding the persistence of hematological and biochemical abnormalities from the acute phase up to 10 years post-infection in SFTS survivors.

  • Evidence before this study Viral infections can induce prolonged abnormal laboratory parameters and persistent symptoms, such as those observed in severe acute respiratory syndrome coronavirus 2 and influenza infections. Existing research on SFTSV infection has predominantly addressed acute-phase abnormalities on laboratory tests, including thrombocytopenia, leukopenia, lymphocytopenia, and concomitant elevations in alanine aminotransferase and aspartate aminotransferase. The long-term prognosis of SFTS survivors remains understudied.

  • New findings Most routine hematological and biochemical parameters typically returned to normal during the recovery phase. However, a subset of individuals exhibited persistent abnormalities, such as thrombocytopenia or elevated liver enzyme levels, which may last for several years after infection.

  • Significance of the study This study provides novel insights into the prognosis of SFTS patients. These findings emphasize the necessity for long-term follow-up and further investigation into the persistent effects of SFTSV infection.

Keywords: Severe fever with thrombocytopenia syndrome (SFTS), Hematological parameters, Blood biochemistry, Cross-sectional study

Abstract

Acute viral infections may lead to long-term adverse health effects. Investigating the hematological and biochemical profiles during recovery can provide valuable insights into the prognosis of severe fever with thrombocytopenia syndrome (SFTS) virus infection. Herein, we performed a cross-sectional analysis of 24 hematological parameters and 12 liver and kidney function-related indicators in 143 naturally infected SFTS patients from the acute phase to 10 years post-recovery. Statistical analyses were performed using the Chi-square test (χ2), Fisher’s exact test, or the ANOVA with Bonferroni correction to assess group differences. Most indicators gradually recovered over time during the recovery period. The decrease in platelet (PLT), white blood cell, neutrophil (NEU), and lymphocyte counts in the acute phase showed a gradual recovery trend from 1–8 months to 6–10 years post-recovery. PLT count levels positively correlated significantly with recovery duration (P = 0.0149). NEU % and thrombocytocrit continued to improve with the recovery time. In addition, some indicators, including platelet distribution width, mean platelet volume, and mean corpuscular hemoglobin concentration, continued to show abnormalities in a certain proportion (12.9 %–69.8 %) of individuals post-recovery. For liver and kidney function-related indicators, acute-phase elevations in aspartate aminotransferase and alanine aminotransferase resolved progressively. Direct bilirubin showed a gradual upward trend over time. Additionally, persistent reductions in total protein and albumin were observed in a subset of recovered individuals. These findings highlight the need for long-term monitoring of SFTS survivors and inform clinical management strategies.

1. Introduction

Since the first discovery of severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) in China in 2010 [1], cases of SFTS have been reported in South Korea [2], Japan [3], Vietnam [4], and other countries in the past years. SFTSV is primarily transmitted through tick bites and via direct contact with the body fluids of infected individuals [5]. However, like most tick-borne viruses, there are currently no approved vaccines and antiviral drugs for the prevention and treatment of SFTS [6,7].

The main clinical features of SFTS include high fever, thrombocytopenia, systemic infection symptoms, and multi-organ dysfunction, with a fatality rate ranging from 12 % to 30 % [1,8]. One study examined laboratory findings in SFTS patients from the acute phase to the recovery phase, identifying common abnormalities during the acute phase, including reduced platelet (PLT), white blood cell (WBC), and lymphocyte (LYM) counts, as well as elevated levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), with some patients exhibiting persistent abnormalities during recovery [9]. However, no studies have been conducted on the long-term prognosis of SFTS patients.

This study analyzes longitudinal clinical laboratory data, including complete blood cell counts and liver and kidney-related biochemical indicators, from the acute phase (≤ 14 days post-onset) to multiple convalescent phases (1 month to 10 years post-onset) in SFTS patients. The findings of this study are expected to provide a more comprehensive understanding of the prognosis of SFTS patients.

2. Material and methods

2.1. Study participants

A total of 143 SFTS patients with natural infection with SFTSV between May 2010 and November 2019 in Huanggang City, Hubei Province, China, were recruited for this study. Epidemiological and demographic data were obtained from the National Disease Surveillance Reporting System. The diagnoses of these 143 cases were made based on the comprehensive analysis of epidemiological history, clinical manifestations, and laboratory tests, as outlined in the Guidelines for the Prevention and Treatment of Severe Fever with Thrombocytopenia Syndrome (2010 edition) published by the National Health Commission [10]. Cases included both suspected and confirmed cases: (1) Suspected cases: Individuals with a history of tick bites or residence in tick-infested areas within 2 weeks before onset, presenting with fever (temperature ≥ 38 °C), accompanied by low PLT and WBC counts, and elevated AST and/or ALT levels. (2) Confirmed cases: Suspected cases meeting ≥ 1 of the following criteria: a) positive nucleic acid test for novel bunyavirus; b) seroconversion or a fourfold increase in immunoglobulin G (IgG) antibody titers during the recovery phase compared to the acute phase; c) SFTSV isolation.

A total of 143 SFTS patients were divided into the acute phase (≤14 days post-onset) and recovery phase (1 month to 10 years post-onset). The clinical laboratory test data from the acute phase of 96 of 143 patients were obtained through case investigation reports. According to the Surveillance Implementation Plan for Severe Fever with Thrombocytopenia Syndrome established by the National Health Commission [10], case investigation reports were conducted for reported cases by professionally trained personnel.

Convalescent patients (n = 143) were categorized into four recovery intervals (1–8 months, 1–3 years, 4–5 years, and 6–10 years) based on the following considerations: a) the immune dynamics observed during long-term recovery from SFTS [11,12]; b) grouping strategies commonly used in studies of long–term recovery following other viral infections [13,14]; and c) the need to balance sample sizes across groups. Whole blood samples were collected from the patients at a single time point during their convalescent period for comprehensive laboratory testing.

2.2. Laboratory testing

Whole blood was collected in K2-ethylenediaminetetraacetic acid (EDTA) tubes and serum in gel coagulation-promoting vacuum tubes from 143 convalescents. These samples were analyzed at the Macheng City Center for Disease Control and Prevention. Twelve biochemical indicators were measured using a fully automated biochemical analyzer (BS-880 model, Shenzhen Mindray), and 24 blood cell count parameters were assessed with an automatic hematology analyzer (URIT-5381 model, URIT). The laboratory's testing capabilities have been validated by the Hubei Province Clinical Testing Center. We used the normal reference ranges provided by the testing institution as the standard for evaluating the results.

2.3. Statistical analysis

Data processing, analysis, and graphing were performed using IBM SPSS Statistics (version 27; IBM, USA), GraphPad Prism (version 9.5; La Jolla, CA), and SAS version 9.4 (SAS Institute, Cary, NC, USA). Non-normally distributed data were expressed as median (interquartile range) (M [IQR]) and the count data were expressed as n (%). The Chi-square test (χ2) or Fisher’s exact test was used for categorical variables, and the ANOVA with Bonferroni correction was applied for continuous variables. Correlations were assessed using a Spearman’s Rank correlation coefficient (r). Multiple linear regression analysis was performed using SAS version 9.4. All tests were two-tailed, and a P < 0.05 was considered statistically significant.

3. Results

3.1. Demographic characteristics

The 143 convalescent patients were categorized into different recovery phases: 1–8 months (median [IQR], 174 [122, 208] days, n = 32), 1–3 years (578 [482, 920] days, n = 44), 4–5 years (1,551 [1,323, 1,852] days, n = 34), and 6–10 years (2,798 [2,461, 3,140] days, n = 33) (Fig. 1, Table 1). Additionally, the median time since symptom onset for the acute-phase cases (n = 96) was 3 (0, 5) days (Table 1).

Fig. 1.

Fig. 1

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Sample collection and demographic distribution of SFTS patients in Huanggang, China (2010–2019). Monthly distribution of sampled SFTS patients from January 2010 to December 2019 in Huanggang, China. Patients were stratified into four recovery phases: 1–8 months, 1–8 months post-onset (n = 32); 1–3 years, ≥1 year but <3 years post-onset (n = 44); 4–5 years, ≥3 years but <5 years post-onset (n = 34); 6–10 years, ≥5 years but <10 years post-onset (n = 33). The color pink represents females and blue represents males. The red arrow represents the sampling date. Abbreviation: SFTS, severe fever with thrombocytopenia syndrome.

Table 1.

Baseline characteristics of SFTS patients during the acute phase and 1–10 years after recovery.

General characteristics Acute phase
(n = 96)		 Recovered phase
 Pa
1–8 months (n = 32) 1–3 years (n = 44) 4–5 years (n = 34) 6–10 years (n = 33)
Age (years), median (IQR) 56 (50, 65) 56 (50, 65) 57 (51, 68) 63 (54, 68) 63 (57, 71) 0.0101
Sex, n (%) 0.9795
Female 53 (55.2) 18 (56.3) 24 (54.5) 20 (58.8) 20 (60.6)
Male 43 (44.8) 14 (43.8) 20 (45.5) 14 (41.2) 13 (39.4)
Median time after symptom onset (days), median (IQR) 3 (0, 5) 174 (122, 208) 578 (482, 920) 1,551 (1,323, 1,852) 2,798 (2,461, 3,140) <0.0001
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a

To calculate the P-values between groups during the recovered phase, one-way ANOVA was used for age, while the Chi-square test was applied to categorical variables. A P-value < 0.05 was considered statistically significant. Abbreviations: SFTS, severe fever with thrombocytopenia syndrome; IQR, interquartile range.

We performed multiple linear regression analysis to assess the effects of age, recovery time, and their interaction. The results showed that age had a significant impact on changes in LYM count, LYM %, neutrophil % (NEU %), urea, creatinine, alkaline phosphatase (ALP), and uric acid (UA) levels. However, the interaction between age and recovery time did not reach statistical significance for these indicators (Table S1).

3.2. Dynamic changes in hematological parameters

We compared hematological parameters related to blood cell counts between the acute phase and various recovery stages (Fig. 2A–E). Numerically, PLT, WBC, NEU, and LYM counts decreased to varying degrees during the acute phase. Compared with the acute phase, most individuals in the recovery phase showed values of PLT, WBC, NEU, and LYM counts restored to within the normal ranges. The values of PLT count in the acute phase were significantly lower than in any recovery group (P < 0.0001), showing a notable increase in the 1–8 months recovery group and continuing to increase through 6–10 years post-recovery (Fig. 2A). The proportion of individuals with PLT counts below the reference range decreased progressively from 87.5 % (84/96) in the acute phase to 32.3 % (10/31) at 1–8 months, 18.6 % (8/43) at 1–3 years, 15.2 % (5/33) at 4–5 years, and 15.2 % (5/33) at 6–10 years post-recovery (Table 2). A positive correlation was observed between PLT levels and recovery time (r = 0.2054, P = 0.0149; Fig. 2B). Similarly, acute-phase WBC counts were significantly lower than in all recovery groups (P < 0.0001), with a trend of gradual increase from 1–8 months to 6–10 years post-recovery (Fig. 2C). WBC abnormality rates dropped from 78.7 % (74/94) in the acute phase to 22.6 % (7/31) at 1–8 months and further to 12.1 % (4/33) at 6–10 years (Table 2). The values of NEU count in the acute phase were significantly lower than in recovery groups beyond 2 years and showed an upward trend from 1–8 months to 6–10 years (Fig. 2D). The abnormal rate of NEU decreased from 78.9 % (45/57) in the acute phase to 16.1 % (5/31) in 1–8 months and 9.1 % (3/33) in 6–10 years (Table 2). Most patients exhibited reduced LYM count during the acute phase, with the majority recovering within 1–8 months post-infection (Fig. 2E). The abnormal rate of LYM count decreased from 41.0 % (25/61) in the acute phase to 3.2 % (1/31) in 1–8 months (Table 2).

Fig. 2.

Fig. 2

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Longitudinal changes in hematologic parameters among SFTS patients from acute phase to 10-year recovery. A) Comparison of PLT counts between the acute phase and recovery periods. B) Correlation between PLT counts and time since disease onset, assessed using Spearman's correlation coefficient. C–E) Comparisons of WBC, NEU, and LYM counts between the acute phase and recovery groups. F) Comparison of other WBC-related parameters across recovery groups. G) Comparison of platelet-associated parameters across recovery groups. H) Comparison of RBC-related parameters across recovery groups. Acute: ≤14 days post-onset (PLT: n = 96; WBC: n = 94; LYM: n = 61; NEU: n = 57. Some data were not collected due to missing records). 1–8 months/1–8 m: 1 to 8 months post-onset (n = 31); 1–3 years/1–3 y: ≥1 but <3 years post–onset (n = 43); 4–5 years/4–5 y: ≥3 but <5 years post-onset (n = 33); 6–10 years/6–10 y: ≥5 but <10 years post-onset (n = 33); with a few individuals lacking available blood samples. Each dot represents an individual; bars indicate the median with IQR. The double-dashed lines denote the normal reference range. If a single dashed line is used, the reference boundary on the opposite side is 0. Statistical analysis was performed using ANOVA with Bonferroni correction, and two-tailed P-values were calculated. Correlations in (B) were assessed using a Spearman’s Rank correlation coefficient (r). P < 0.05 was considered statistically significant. Abbreviations: PLT, platelet; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; MON, monocytes; EO, eosinophils; BASO, basophils; PCT, thrombocytocrit; P_LCC, platelet large cell count; P_LCR, platelet large cell ratio; PDW, platelet distribution width; MPV, mean platelet volume; RBC, red blood cell; RDW-CV, red blood cell distribution width-coefficient of variation; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; IQR, interquartile range.

Table 2.

Abnormality rate of major acute-phase laboratory markers among SFTS survivors at 1–10 years post-infection.

Laboratory markers Reference range Acute phase
(n = 96)
 Recovered phasea
 Pb value P value (acute vs. 1–8 months) P value (acute vs. 1–3 years) P value (acute vs. 4–5 years) P value (acute vs 6–10 years)
1–8 months
(n = 32)
 1–3 years
(n = 44)
 4–5 years
(n = 34)
 6–10 years
(n = 33)
Below
no./total no. (%)		 Above no./total no. (%) Below
no./total no. (%)		 Above no./total no. (%) Below
no./total no. (%)		 Above no./total no. (%) Below
no./total no. (%)		 Above no./total no. (%) Below
no./total no. (%)		 Above no./total no. (%)
PLT (×109/L) 100–300 84/96 (87.5) 0 10/31
(32.3)		 1/31
(3.2)		 8/43
(18.6)		 2/43
(4.7)		 5/33
(15.2)		 2/33
(6.1)		 5/33
(15.2)		 1/33
(3.0)		 0.3952 <0.0001 <0.0001 <0.0001 <0.0001
WBC (×109/L) 4–10 74/94
(78.7)		 1/94
(1.1)		 7/31
(22.6)		 0 8/43
(18.6)		 0 7/33
(21.2)		 1/33
(3.0)		 4/33
(12.1)		 1/33
(3.0)		 0.7922 <0.0001 <0.0001 <0.0001 <0.0001
NEU (109/L) 2–7 45/57
(78.9)		 3/57
(5.3)		 5/31
(16.1)		 0 7/43
(16.3)		 1/43
(2.3)		 6/33
(18.2)		 2/33
(6.1)		 3/33
(9.1)		 0 0.4294 <0.0001 <0.0001 <0.0001 <0.0001
LYM (×109/L) 0.8–4.0 25/61
(41.0)		 3/61
(4.9)		 1/31
(3.2)		 1/31
(3.2)		 3/43
(6.9)		 0 2/33
(6.1)		 0 1/33
(3.0)		 0 0.9251 0.0001 <0.0001 <0.0001 <0.0001
AST (U/L) 0–40 0 44/56
(78.6)		 0 5/29
(17.2)		 0 5/41
(12.2)		 0 2/27
(7.4)		 0 13/29
(44.8)		 0.0013 <0.0001 <0.0001 <0.0001 0.0017
ALT (U/L) 0–40 0 35/56
(62.5)		 0 4/29
(13.8)		 0 1/41
(2.4)		 0 2/27
(7.4)		 0 0 0.0904 <0.0001 <0.0001 <0.0001 <0.0001
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a

Sample size for blood cell counts: 1–8 months (n = 31), 1–3 years (n = 43), 4–5 years (n = 33), 6–10 years (n = 33). Missing data due to incomplete samples. The number of samples used for liver and kidney function indicators analysis: 1–8 months (n = 29), 1–3 years (n = 41), 4–5 years (n = 27), 6–10 years (n = 29), with a few individuals lacking available blood samples.

b

P-values were calculated using the Chi-square test or Fisher’s exact test to compare SFTS convalescents at 1–8 months, 1–3 years, 4–5 years, and 6–10 years post-infection. Two-tailed P-values were calculated.

Abbreviations: no., number; SFTS, severe fever with thrombocytopenia syndrome; PLT, platelet; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

We also assessed the recovery of other blood cell–related parameters across the different recovery groups (Fig. 2F–H). Most of these parameters, including monocyte count, monocyte %, eosinophil count, eosinophil %, basophil count, basophil %, platelet large cell ratio, and large platelet cell count, returned to within normal ranges in the recovery phase (Fig. 2F–G, Table 3). Additionally, the NEU % exhibited a gradual increase from 1–8 months to 6–10 years, with the proportion of individuals below the normal range decreasing from 22.6 % (7/31) to 15.2 % (5/33) (Fig. 2F, Table 3). The abnormal rate of LYM % across recovery groups ranged from 21.2 % (7/33) to 39.5 % (17/43) (Fig. 2F, Table 3). Thrombocytocrit also showed a gradual recovery from 1–8 months to 6–10 years, with the abnormal rate decreasing from 51.6 % (16/31) to 36.4 % (12/33) (Fig. 2G, Table 3). A notable proportion of individuals had platelet distribution width values below the normal range across all recovery groups, with abnormal rates ranging from 45.2 % (14/31) to 69.8 % (30/43) (Fig. 2G, Table 3). The abnormal rate of mean platelet volume ranged from 12.9 % (4/31) to 32.6 % (14/43) (Fig. 2G, Table 3). Red blood cell counts and most related parameters (including hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin) were restored to normal ranges in the majority of individuals (Fig. 2H, Table 3). Nevertheless, a subset of individuals remained outside the normal ranges. The abnormal rate of red blood cell count ranged from 9.1 % (3/33) to 23.3 % (10/43); for hemoglobin, from 14.0 % (6/43) to 25.3 % (8/31); for hematocrit, from 21.2 % (7/33) to 36.4 % (12/33); for mean corpuscular volume, from 11.6 % (5/43) to 20.7 % (8/33); and for mean corpuscular hemoglobin, from 9.3 % (4/43) to 15.2 % (5/33). The abnormal rate of mean corpuscular hemoglobin concentration ranged from 39.4 % (13/33) to 58.1 % (25/43), and the red cell distribution width–coefficient of variation ranged from 18.2 % (6/33) to 30.3 % (10/33).

Table 3.

Abnormality rate of hematological and biochemical parameters in SFTS survivors at 1–10 years post-infection.

Parameters Reference range Recovered phasea
 P valueb
1–8 months
(n = 32)
 1–3 years
(n = 44)
 4–5 years
(n = 34)
 6–10 years
(n = 33)
Below
no./total no. (%)		 Above
no./total no. (%)		 Below
no./total no. (%)		 Above
no./total no. (%)		 Below
no./total no. (%)		 Above
no./total no. (%)		 Below
no./total no. (%)		 Above
no./total no. (%)
Blood cell count
LYM (%) 20–40 1/31 (3.2) 8/31 (25.8) 8/43 (18.6) 9/43 (20.9) 4/33 (12.1) 3/33 (9.1) 4/33 (12.1) 5/33 (15.2) 0.3610
MON (×109/L) 0.12–1.2 0 0 1/43 (2.3) 0 0 0 0 0 0.9999
MON (%) 3–12 0 0 1/43 (2.3) 0 0 1/33 (3.0) 0 0 0.9999
NEU (%) 50–70 7/31 (22.6) 1/31 (3.2) 7/43 (16.3) 11/43 (35.5) 5/33 (15.2) 4/33 (12.1) 5/33 (15.2) 6/33 (18.2) 0.4321
EOS (×109/L) 0.02–0.50 0 0 1/43 (2.3) 1/43 (2.3) 1/33 (3.0) 2/33 (6.1) 0 2/33 (6.1) 0.4578
EOS (%) 0.5–5.0 2/31 (6.5) 4/31 (12.9) 1/43 (2.3) 3/43 (7.0) 1/33 (3.0) 7/33 (21.2) 0 5/33 (15.2) 0.3490
BASO (×109/L) 0–0.1 0 0 0 0 0 0 0 0 –
BASO (%) 0–1 0 0 0 0 0 0 0 0 –
MPV (fL) 6.5–12.0 4/31 (12.9) 0 14/43 (32.6) 0 9/33 (27.3) 0 9/33 (27.3) 0 0.2837
PDW (fL) 9–17 14/31 (45.2) 1/31 (3.2) 30/43 (69.8) 1/43 (2.3) 18/33 (54.5) 3/33 (9.1) 19/33 (57.6) 0 0.2067
PCT (%) 0.108–0.282 16/31 (51.6) 0 21/43 (48.8) 0 15/33 (45.5) 0 12/33 (36.4) 0 0.6221
P_LCR (%) 9–45 0 1/31 (3.2) 2/43 (4.7) 2/43 (4.7) 0 3/33 (9.1) 0 1/33 (3.0) 0.6183
P_LCC (×109/L) 13–129 2/31 (6.5) 0 3/43 (7.0) 0 0 0 1/33 (3.0) 0 0.4524
RBC (1012/L) Male: 4.0–5.5; Female: 3.5–5.0 2/31 (6.5) 5/31 (16.1) 0 10/43 (23.3) 0 7/33 (21.2) 0 3/33 (9.1) 0.4020
HGB (g/L) Male: 130–175; Female: 115–150 5/31 (16.1) 3/31 (9.7) 3/43 (7.0) 3/43 (7.0) 4/33 (12.1) 3/33 (9.1) 5/33 (15.2) 2/33 (6.1) 0.6377
HCT (%) Male: 40–50; Female: 35–45 3/31 (9.7) 7/31 (22.6) 1/43 (2.3) 9/43 (20.9) 3/33 (9.1) 9/33 (27.3) 4/33 (12.1) 3/33 (9.1) 0.4462
MCV (fL) 80–100 2/31 (6.5) 2/31 (6.5) 0 5/43 (11.6) 3/33 (9.1) 2/33 (6.1) 4/33 (12.1) 1/33 (3.0) 0.9601
MCH (pg) 27–34 2/31 (6.5) 1/31 (3.2) 0 4/43 (9.3) 4/33 (12.1) 0 5/33 (15.2) 0 0.8679
MCHC (g/L) 320–360 14/31 (45.2) 0 25/43 (58.1) 0 17/33 (51.5) 0 13/33 (39.4) 0 0.4046
RDW_CV % 11–16 8/31 (25.8) 0 8/43 (18.6) 0 10/33 (30.3) 2/33 (6.1) 6/33 (18.2) 0 0.2529
Liver and kidney variables
UREA (mmol/L) 1.8–7.5 0 1/29 (3.4) 0 0 0 1/27 (3.7) 0 2/29 (6.8) 0.3736
CREA (μmol/L) 30–110 0 1/29 (3.4) 0 0 0 0 0 2/29 (6.8) 0.2266
TP (g/L) 55–80 0 8/29 (27.6) 0 11/41 (26.8) 0 7/27 (25.9) 0 13/29 (44.8) 0.3324
ALP (U/L) 0–130 0 0 0 2/41 (4.9) 0 1/27 (3.7) 0 0 0.4809
UA (μmol/L) 143–444 0 1/29 (3.4) 0 1/41 (2.4) 0 1/27 (3.7) 0 2/29 (6.8) 0.9238
CO2-CP (mmol/L) 20.1–30.0 0 0 2/41 (4.9) 0 2/27 (7.4) 0 1/29 (3.4) 0 0.5781
DBIL (μmol/L) 0–8.6 0 2/29 (6.9) 0 4/41 (9.8) 0 5/27 (18.5) 0 5/29 (17.2) 0.4721
TBIL (μmol/L) 0–21 0 0 0 2/41 (4.9) 0 1/27 (3.7) 0 1/29 (3.4) 0.8381
γ-GT (U/L) 0–50 0 1/29 (3.4) 0 2 (4.9) 0 5/27 (18.5) 0 3/29 (10.3) 0.2056
ALB (g/L) 35–50 0 6/29 (20.7) 0 13 (31.7) 0 3/27 (11.1) 0 11/29 (37.9) 0.0961
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Abbreviations: no., number; SFTS, severe fever with thrombocytopenia syndrome; NEU, neutrophil; LYM, lymphocyte; MON, monocytes; EO, eosinophils; BASO, basophils; PCT, thrombocytocrit; P_LCC, platelet large cell count; P_LCR, platelet large cell ratio; PDW, platelet distribution width; MPV, mean platelet volume; RBC, red blood cell; RDW-CV, red blood cell distribution width-coefficient of variation; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; TP, total protein; ALB, albumin; TBIL, total bilirubin; IBIL, indirect bilirubin; ALP, alkaline phosphatase; UREA, urea; UA, uric acid; CREA, creatinine; CO2-CP, CO2 combining power; γ-GT, γ-glutamyl transferase.

a

The number of convalescents used for blood cell count testing (1–8 months: n = 31; 1–3 years: n = 43; 4–5 years: n = 33; 6–10 years: n = 33); the number of convalescents used for liver and kidney indicators testing (1–8 months: n = 29; 1–3 years: n = 41; 4–5 years: n = 27; 6–10 years: n = 29).

b

The P-value was calculated using Chi-square or Fisher’s exact test to compare the SFTS convalescent groups at 1–8 months, 1–3 years, 4–5 years, and 6–10 years post-onset. The two-tailed P-value was calculated.

3.3. Dynamic changes in liver and kidney function indicators

We further compared liver and kidney function-related indicators, such as AST and ALT, between the acute phase and recovery stages. Compared with the acute phase, most individuals in the recovery phase showed values returning to within the normal range (Fig. 3A and 3B). AST levels were significantly elevated in the acute phase but largely normalized by 1–8 months post-recovery (Fig. 3A). The abnormal rate of AST decreased from 78.6 % (44/56) in the acute phase to 17.2 % (5/29) in 1–8 months, 12.2 % (5/41) in 1–3 years, and 7.4 % (2/27) in 4–5 years, but increased to 44.8 % (13/29) in 6–10 years (Table 2). ALT levels were also significantly higher in the acute phase and largely returned to normal range in the recovery phase (Fig. 3B). The proportion of individuals with ALT above the normal range decreased from 62.5 % (35/56) in the acute phase to 13.8 % (4/29) at 1–8 months, 2.4 % (1/41) at 1–3 years, 7.4 % (2/27) at 4–5 years, and 0 % (0/29) at 6–10 years (Table 2).

Fig. 3.

Fig. 3

Open in a new tab

Longitudinal changes in biochemical parameters among SFTS patients from acute phase to 10-year recovery. A) AST levels during the acute and recovery phases. B) ALT levels during the acute and recovery phases. C) Comparison of other liver and kidney function-related indicators across different recovery phases. Acute: ≤14 days post-onset (AST and ALT: n = 56; some data were not collected due to missing records). 1–8 months/1–8 m: 1 to 8 months post–onset (n = 29); 1–3 years/1–3 y: ≥1 but <3 years post–onset (n = 41); 4–5 years/4–5 y: ≥3 but <5 years post-onset (n = 27); 6–10 years/6–10 y: ≥5 but <10 years post-onset (n = 29); with a few individuals lacking available blood samples. Each dot represents an individual; bars represent the median with IQR. Double dashed lines indicate normal reference range. If only a single dashed line is shown, the other reference boundary is 0. P values were calculated using ANOVA with Bonferroni correction, and two-tailed P values are shown. P < 0.05 was considered statistically significant. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; TBIL, total bilirubin; IBIL, indirect bilirubin; ALP, alkaline phosphatase; UREA, urea; UA, uric acid; CREA, creatinine; CO2-CP, CO2 combining power; γ-GT, γ-glutamyl transferase; IQR, interquartile range.

We also assessed additional liver and kidney function-related parameters (including total bilirubin, alkaline phosphatase, carbon dioxide combining power, urea, uric acid, gamma-glutamyl transpeptidase, and creatinine which generally showed values within the normal range in most individuals across all recovery groups (Fig. 3C). However, direct bilirubin (DBIL) showed a slight upward trend over time, with the abnormal rate increasing from 6.9 % (2/29) in 1–8 months group to 17.2 % (5/33) in the 6–10 years group (Table 3). A considerable proportion of convalescents also had total protein (TP) and albumin (ALB) levels above the normal range, with abnormality rates ranging from 25.9 % (7/33) to 44.8 % (13/33) for TP and 11.1 % (3/33) to 37.9 % (11/33) for ALB (Table 3).

4. Discussion

Acute viral infections can cause lasting adverse health effects. For instance, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are associated with long-term post-recovery syndromes known as “long-term effects of ‌coronavirus disease 2019 (COVID-19) (long COVID-19)” and “long flu”, respectively [13,15,16]. In our previous two-year longitudinal study on COVID-19 convalescents, we found that although most laboratory parameters improved during recovery, certain abnormalities persisted [13]. Similarly, a five-year follow-up study of Ebola survivors revealed that 59 % continued to experience at least one adverse symptom, with 29 % reporting a significant impact on daily life [14]. During the acute phase of SFTSV infection, patients may experience a range of symptoms, including gastrointestinal disturbances, neurological manifestations, hemorrhagic features, and multi-organ dysfunction [17,18]. Beyond the acute phase, the long-term health status of survivors also warrants attention. To address this, we investigated changes in laboratory parameters over up to ten years following acute SFTSV infection.

Our findings indicated that during the acute phase, patients exhibited reduced levels of PLT, WBC, NEU, and LYM counts, consistent with previous studies [1,9]. One study linked PLT reduction to arginine deficiency [19], while another suggested that SFTSV can bind directly to platelets, facilitating their recognition and phagocytosis by splenic macrophages [20]. The early decline in WBCs may be attributed to the SFTSV targeting monocytes and B cells [21,22], and suppression of monocyte apoptosis has also been shown to impair lymphocyte differentiation and maturation [23]. These mechanisms may underlie the observed leukopenia and thrombocytopenia in the acute phase. Since WBCs play a critical role in immune responses and PLTs are key for coagulation, their reduction reflects impaired immune and hematologic function [24]. Our results showed that PLT- and WBC-related parameters gradually returned to normal ranges over time in most individuals, but PLT count exhibited a significant positive correlation with recovery duration (P = 0.0149). Abnormalities in PLT- and WBC-related parameters were still present in a subset of individuals even years after recovery, highlighting the need for continued monitoring of their long-term immune and hematologic function.

As a pantropic virus, SFTSV can infect multiple organs and tissues, including the bone marrow. Previous studies have reported SFTSV-associated hemophagocytic activity and even cases of multiple myeloma [[25], [26], [27]], and persistent viral replication has been observed in the bone marrow of infected rhesus macaques [28]. MPV and PDW are commonly used markers of platelet production and function, reflecting bone marrow activity [29]. Interestingly, sustained reductions in PLT, MPV, and PDW were observed in a subset of SFTS survivors in our study, suggesting that platelet production may remain impaired long after recovery. These observations underscore the potential for long-term bone marrow suppression following SFTSV infection. Accordingly, we recommend extended follow-up of hematological parameters, particularly PLT, MPV, and PDW, in recovered patients. When abnormalities persist, further evaluation with bone marrow biopsy and functional assessments should be considered to better understand and manage potential hematopoietic dysfunction.

AST and ALT are key biomarkers of liver and kidney injury. We found that these enzymes were elevated in most acute-phase cases, aligning with previous studies [1,9]. SFTSV has been shown to cause severe liver and kidney damage [[30], [31], [32]]. In vitro experiments have demonstrated SFTSV replication in Huh7 cells (a human hepatoma cell line) [30], and infection of hepatic epithelial cells induces proinflammatory cytokines and chemokines via NF-κB signaling, contributing to liver damage [31]. The viral NSs protein suppresses antiviral IFN-β responses while enhancing NF-κB activation, exacerbating liver inflammation [31]. Animal studies have confirmed SFTSV replication in multiple organs, including the liver, intestine, kidney, and spleen, in IFNAR−/− mice [33]. SFTSV infection can also lead to acute kidney injury, with viral RNA detectable in urine and a significantly higher case fatality rate among acute kidney injury patients [34,35]. Both direct viral damage and drug-induced toxicity may contribute to organ dysfunction during hospitalization.

During recovery, most liver and kidney parameters, such as urea, creatinine, alkaline phosphatase, uric acid, and total bilirubin, returned to normal. AST and ALT levels also normalized over time in many convalescents. However, some parameters, such as TP and ALB, remained persistently elevated in a proportion of individuals, warranting further attention to their long-term liver and kidney function. We observed a gradual increase in DBIL levels over time, which may be related to aging [36] or chronic alcohol consumption [37]. Notably, AST levels were significantly elevated in individuals 6–10 years post-recovery, potentially due to older age [38], lifestyle factors such as long-term alcohol use [[39], [40], [41]], or long-term medication use (e.g., statins like atorvastatin) [42].

Multiple mechanisms may underlie SFTSV-induced long-term liver injury. In SFTSV-infected individuals, elevated levels of inflammatory cytokines such as IL-8, IP-10, IL-10, and IL-6 have been observed between 22–180 days post-infection and even during extended recovery periods [43,44]. Persistent systemic inflammation may contribute to the pathogenesis of long-term liver damage. Similarly, in patients with long COVID-19, particularly those over 65 years old, significantly elevated fasting ALT and AST levels have been reported, indicating prolonged hepatic effects of SARS-CoV-2 infection [45]. In addition, pre-existing comorbidities (e.g., cardiovascular disease) have been associated with more pronounced liver injury following viral infection, suggesting that underlying health conditions may exacerbate hepatic responses to infection [45]. The severity of the acute phase and the use of hepatotoxic antiviral medications may also influence long-term outcomes [46]. Taken together, these findings highlight the need for long-term liver health surveillance in convalescent patients, especially the elderly and those with underlying comorbidities.

SARS-CoV-2 infection is known to cause “long COVID-19” [47]. In our previous research, we conducted a study on laboratory markers two years after SARS-CoV-2 infection and found that most patients had recovered or showed improvements in their complete blood count and liver and kidney function indicators within two years, which is consistent with the long-term recovery characteristics observed in SFTS [13]. However, unlike SARS-CoV-2, SFTSV infection leads to a significant reduction in PLT count during the acute phase, and recovery to normal reference ranges is positively correlated with recovery time, often taking several years. Therefore, we recommend the establishment of a systematic long-term follow-up mechanism for SFTS and other highly pathogenic virus convalescents, focusing on the monitoring of hematological and immune function indicators to facilitate early detection and intervention of potential chronic damage. In particular, for SFTS convalescents, it is crucial to assess platelet production and function recovery to more comprehensively evaluate the long-term restoration of the hematopoietic system.

To reduce the risk of long-term health consequences following acute SFTSV infection, targeted measures should be implemented. First, raising awareness of self-protection among high-risk populations is critical for infection prevention [48,49]. Moreover, there is an urgent need to develop effective vaccines and antiviral therapies [50,51]. Vaccination in endemic areas and among susceptible populations may induce long-lasting antibody and T cell immunity, thereby reducing the risk of infection and mitigating long-term health outcomes [[52], [53], [54]]. Antiviral agents may shorten disease duration and reduce acute-phase organ damage, thus lowering the likelihood of persistent abnormalities.

This study has several limitations. Due to the novelty of the virus, collecting samples from patients recovered for up to ten years was challenging, resulting in a limited sample size. This limitation prevented complete age balance among the study groups. To further investigate the mechanisms by which age affects the relevant indicators, future research should expand the sample size and conduct age subgroup analyses to obtain more comprehensive and scientifically robust conclusions. Additionally, although SFTSV is known to cause multi-organ dysfunction syndrome, we did not evaluate cardiac function parameters. Moreover, as this was a cross-sectional study, future longitudinal follow-up of acute cases is recommended to minimize individual variability and better assess long-term outcomes. Finally, among the 143 cases, only 96 had recorded acute-phase data (such as PLT, WBC, and NEU counts, as well as AST and ALT levels). This discrepancy may introduce some bias when comparing laboratory parameters between the acute and convalescent phases. However, previous studies have reported that PLT, WBC, NEU, AST, and ALT levels typically exhibit abnormal decreases or increases during the acute phase in most patients. Therefore, the absence of acute-phase data in some individuals is unlikely to significantly affect the overall analysis.

5. Conclusion

This study comprehensively analyzed hematological and liver/kidney function parameters in SFTS patients from the acute phase to up to ten years post-recovery. While most laboratory indicators normalized over time, certain abnormalities persisted in a subset of individuals, warranting further investigation into their long-term health implications. Our findings provide insights into the prognosis of SFTS patients and highlight the need for broader follow-up studies and long-term cohort research to better understand the sustained impact of SFTSV infection.

Ethics statement

This study was approved by the Ethics Committee of the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (IVDC2021-006). All study participants provided written informed consent.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2022YFC2604100), the National Natural Science Foundation of China (92269203), and the R&D Program of Guangzhou National Laboratory (SRPG23-005).

Conflcit of interest statement

The authors declare that there are no conflicts of interest.

Author contributions

Min Li: Writing – original draft, Software, Methodology, Formal analysis, Data curation. Yalan Wang: Writing – original draft, Software, Formal analysis, Data curation. Peiwen Qiao: Data curation. Yaxin Guo: Formal analysis. Peipei Guo: Formal analysis. Tian Ma: Formal analysis. Shaobo Dong: Resources. Jianbo Zhan: Resources. Jun Liu: Writing – review & editing, Supervision, Project administration, Funding acquisition, Conceptualization. Guizhen Wu: Supervision, Project administration, Funding acquisition, Conceptualization.

Footnotes

Supplementary data to this article can be found online at https://doi.org/10.1016/j.bsheal.2025.05.007.

Contributor Information

Jianbo Zhan, Email: jbzhan8866@163.com.

Jun Liu, Email: liu_jun01@gzlab.ac.cn.

Guizhen Wu, Email: wugz@ivdc.chinacdc.cn.

Supplementary data

The following are the Supplementary data to this article:

Supplementary Data 1
mmc1.docx (26.7KB, docx)

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