{"paper_id":"a2bf11a5-a099-4ec9-928b-eb78456d1a61","body_text":"Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients:A Prospective, Multicenter 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 Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients:A Prospective, Multicenter Study Li-Fen Hu, Ting-Ting Bian, Qiang Chen, Meng-Yu Liu, Jia-Jia Li, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3873036/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. Methods. A multicenter cohort study was performed to determine SFTS virus (SFTSV) level from blood, throat swabs, fecal/ anal swabs, urine and bedside environment swabs of SFTS patients by qRT-PCR. PPEs were applied in healthcare workers based on the pathway of SFTSV shedding and occurrence of hemorrhagic signs in patients. Results. A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57%). Positive SFTSV in throat swabs (T-SFTSV), fecal /anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02%), 91 (48.15%) and 65 (34.4%) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients ( P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions. Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed. Severe fever with thrombocytopenia syndrome virus Dabie bandavirus Shedding Precaution measures Multicenter study Human-to-human Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Intruduction Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by SFTS virus (SFTSV) belonging to Bunyavirales order, Pheniviridae family, Bandavirus genus [ 1 , 2 ], which was renamed as Dabie bandavirus (DBV) by the International Committee on Taxonomy of Viruses in 2019 [ 2 ]. In recent years, SFTS has been rapidly spreading in Asia including China, Japan, South Korea, Vietnam, Pakistan, and Myanmar [ 3 – 8 ]. The public health concern of SFTSV is primarily posed by the wide distribution of its vectors (ticks) and the broad spectrum of its hosts [ 9 ]. Haemaphysalis longicornis ( H. longicornis ) tick is the main reservoir and vector of SFTSV, which although native to East Asia, has established populations in the Australasian and Western Pacific Regions [ 9 ]. Although most persons with SFTS experience nonspecific influenza-like symptoms, more severe and prolonged disease can occur in severe ill patients. Severe infection is associated with high-grade viremia and excessive inflammatory response, further leading to organ damage, nervous system disorders, blood clotting abnormalities, and secondary infection in severe patient. The case fatality rate of critically ill patients is up to 10%-50% [ 10 – 13 ]. Due to its high fatality and the possibility of causing pandemic transmission, SFTS was listed among the top 10 priority infectious disease with urgent need for research by the World Health Organization in 2017 [ 14 ]. The SFTSV infection was primarily transmitted from infected tick to human. In addition to tick transmission, human-to-human transmission of SFTS had been widely reported and mostly caused by unprotected exposure to individuals with SFTS disease [ 15 – 33 ]. A strong risk factor linked to human-to-human SFTSV spread is contact with infected bodily fluids. However, there is still a dearth of knowledge regarding the infection routes and related factors that might affect the human-to-human transmission of SFTSV without a comprehensive evaluation of the viral shedding pattern. Research on specific precaution measures against SFTSV human-to-human transmission infection are becoming impending demand. In the present prospective multicenter study, SFTSV shedding pattern from organs connected to the outside in severely ill patients were evaluated. Precaution measures were applied for healthcare workers (HCWs) exposed to critically ill SFTS patients. The relationship between virus distribution with comorbidities of patients and human-to-human transmission events were analyzed. The result would be important for effective control strategies against SFTSV human-to-human transmission. Materials and Methods Study Design and Participants A multicenter cohort study was performed in three sentinel hospitals for SFTS in Anhui province, including the First Affiliated Hospital of Anhui Medical University, the Chaohu Affiliated Hospital of Anhui Medical University and Lu'an People's Hospital of Anhui Medical University from April 2020 to October 2022. We enrolled patients (≥ 18 years and < 80 years of age) who were hospitalized and confirmed as SFTSV infection by positive polymerase-chain reaction (PCR) detection of blood samples. Patients of younger than 18 years old, with chronic respiratory disease, gastrointestinal diseases and chronic kidney disease were excluded. According to the guidelines for the prevention and treatment of fever with thrombocytopenia syndrome by a standard criterion released by the Chinese Ministry of Health[ 34 ], patients were diagnosed as having mild illness, severe or critical ill form of disease. All the SFTS patients were underwent chest radiography or chest computed tomography (CT) during the disease course. The study protocol was approved by the Human Ethics Committee of Anhui Medical University (20200980). Informed consent was obtained from all patients, in accordance with the Declaration of Helsinki. Virological Investigations SFTSV infection was confirmed in all patients by testing serum specimens with a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. At the stage of disease progression of patients, the blood, throat swab, anal swab, urine and bedside environment swab samples of the patients were collected for SFTSV detection. RNA was extracted from these samples using the high-purity viral RNA kit (Omega, Guangzhou, China) according to the manufacturer’s instructions. SFTSV RNA was amplified using specific primers and probes by RT-PCR under conditions previously described using the SFTSV nucleic acid quantitative detection Kit (DaAn Gene Co, Guangzhou, China) [ 35 ]. Personal protective equipment use of healthcare workers Different PPEs were applied in HCWs according to exposure risks. The single-use medical masks were used in HCWs contacting with mild SFTS patients. The gloves and surgical mask with face shield were used in HCWs exposed to SFTS patients with hemorrhagic manifestations and positive T-SFTSV. The gloves, surgical mask or medical protective mask and face shield were applied by HCWs participation in cardiopulmonary resuscitation (CPR). The disposable hat, latex gloves, medical protective mask with face shield were applied by HCWs in participation of orotracheal intubation for severely ill patients with positive T-SFTSV. Besides, mask oxygen inhalation was used in critically ill patients with bloody secretions of oral or nasal and positive T-SFTSV. The ward environment was disinfected with 1000mg/L chlorine and ultraviolet radiation for more than 30 minutes after the patient was discharged. Data collection of SFTS patients Hospital-based data were collected during the hospitalization by using a standardized medical questionnaire. A medical record review was performed to collect information on epidemiologic, clinical manifestations, signs of haemorrhage and laboratory parameters. Personal protective equipment (PPE) use of HCWs and occurrence of SFTSV human-to-human event among the patients were also recorded. Statistical Analysis Data were analyzed using SPSS, version 20.0 (SPSS Inc., USA). Quantitative variables were expressed as means ± standard deviation (SD) or as medians (interquartile range), categorical variables were expressed as the number (percentage). Student's t test was applied when normality assumptions were satisfied; otherwise, the equivalent non-parametric test was used. A chi-square test was used to examine the difference in the percentage of categorical variables. Graphpad prism 5 software was used to compare values in groups and calculate the correlation coefficients and significance values of two variables. The correlation analysis of Log10 (SFTSV) level in blood with that from other samples was calculated using the methods of the Pearson correlation coefficient. A two-sided p -value < 0.05 was considered statistically significant. Results Characteristics of Viral shedding from SFTS patients One hundred and eighty-nine SFTS patients were included in the study, the median age was 62.5 years, 83 (43.9%) patients were male and 106 (56.1%) were female. Fifty-four patients died (case fatality rate, 28.57%). The median SFTSV load was 9.6 x10 3 copies/mL [interquartile range (IQR) 3.6x10 3 − 1.6 x10 4 ] in blood (B-SFTSV) in 23 mild patients, 8.3 x10 5 copies/mL [interquartile range (IQR) 1x10 5 − 5.2 x10 6 ] in blood (B-SFTSV) in 166 severely ill ( p = 0.001). Positive SFTSV in throat swabs (T-SFTSV) were detected in 121 (64.02%) severely ill patients with median load 2.1 x10 3 copies/mL (IQR 1.2x10 3 − 8.1 x10 3 ). Positive SFTSV in fecal /anal swabs (F-SFTSV) were detected in 91 (48.15%) severely ill patients with median load 1.3 x10 3 copies/mL (IQR 1.0x10 3 − 3.0 x10 3 ). Positive SFTSV in urine (U-SFTSV) were detected in 65 (34.4%) severely ill patients with median load 1.5 x10 3 copies/mL (IQR 1.0x10 3 − 2.8 x10 3 ). No positive T-SFTSV, F-SFTSV and U-SFTSV were detected in 23 mild SFTS patients. The viral load of blood samples (N = 121) is significantly higher than those of throat swabs (N = 121), anal swabs (N = 91) and urine (N = 65) ( P < 0.0001), the viral load of throat swabs is significantly higher than that of anal swabs ( P < 0.001) (Fig. 1). The results showed positive correlations of SFTSV levels in blood with throat swabs (r = 0.4535, P < 0.0001), anal swabs (r = 0.3263, P = 0.0016), and urine (r = 0.4102, P = 0.0007), respectively (Fig. 1). It is noteworthy that positive SFTSV of bedside environment swab was detected in two fatal patients with pneumonia, besides, one had oral hemorrhage, the other one had cough and expectoration. Our research demonstrated SFTSV could shed out not only the blood, but from oropharynx, feces and urine in severely ill patients with high viral load (Fig. 2 ). A: Comparison of SFTSV levels from different samples; B: Correlations of SFTSV levels in blood with throat swabs; C: Correlations of SFTSV levels in blood with anal swabs; D: Correlations of SFTSV levels in blood with urine; The viral levels were in the format of Log10 viral RNA copies/mL. *** P < 0.0001. SFTSV: severe fever with thrombocytopenia syndrome virus. Figure 1 Correlations of SFTSV load in blood with throat swabs, anal swabs and urine in patients with severe fever with thrombocytopenia syndrome Correlations between clinical phenotypes and SFTSV distribution in patients Pneumonia occurred in 73 (60.3%) patients with positve-SFTSV in throat swabs, significantly higher than in 13 (19.1%) patients with negative-SFTSV in throat swabs ( P < 0.0001). Diarrhea occurred in 69 (75.8%) patients with positve-SFTSV in anal swabs, in 42 (42.8%) patients with negative-SFTSV in anal swabs ( P < 0.0001). Acute kidney injury (AKI) occurred in 61 (93.8%) patients with positve-SFTSV in urine, in 13 (7.7%) patients with negative-SFTSV in urine ( P < 0.0001)(Fig. 3). The levels of estimated glomerular filtration rate (eGFR) in patients with SFTSV in urine were significantly lower than that in negative-SFTSV urine group (52.1 ± 28.8 vs 91.3 ± 22.2, p < 0.0001). Among the 166 severely ill patients, 43 patients had cough, 13 patients had hemoptysis and 26 patients had oropharyngeal bleeding. All the patients with cough and oral or nasal bleeding had positive SFTSV of throat swabs, which is significantly higher than the patients without these presence. SFTSV: severe fever with thrombocytopenia syndrome virus AKI: Acute kidney injury Figure 3 Correlations between comorbidities and SFTSV distribution in severely ill patients with severe fever with thrombocytopenia syndrome Correlation between case fatality rate and SFTSV distribution in patients Among 54 patients who developed fatal outcome, the median SFTSV load was 7.2 x10 6 copies/mL [interquartile range (IQR) 1.6x10 6 − 3.2 x10 7 ] in blood (B-SFTSV). Positive SFTSV detection was determined in all (54) of throat swabs, 88.89% (48/54) of anal swabs, 79.63% ( 43/54) of the urine samples, all significantly higher than the positive rate obtained from the non-fatal cases (0%, 31.85% and 16.29%, respectively, all P < 0.0001) (Fig. 4). Among 61 patients who had simultaneously positive results in all throat swabs, anal swabs and urine samples, 43 fatal patients had positive SFTSV for all sample types, which is significantly higher than the survived patients. SFTSV: severe fever with thrombocytopenia syndrome virus Figure 4 Difference of SFTSV distribution between death group and non-death group in severe ill SFTS patients Precaution measures and incidence of SFTSV human-to-human transmission In this research, a human-to-human transmission was identified with altogether 7 patients involved. The index case had SFTSV load of 9 x10 6 copies/mL in plasma sample, 1.2 x10 5 copies/mL in the throat swab, 2.4 x10 3 copies/mL in the anal swab, and 2.2 x10 3 copies/mL in urine. Among the eight persons exposure to the hemorrhagic patient with cardiopulmonary resuscitation (CPR) and orotracheal intubation bleeding, six persons were infected without tick exposure history. None of the six infected patients worn face shield as personal protective equipment. By contrast, two HCWs who had close contact with the index case including sputum suction and bleeding treatment were all samples test negative for SFTSV, one had worn double surgical masks with face shield, the other one wearing N95 mask in cardiopulmonary resuscitation (CPR) for more than 1 hour. As in Fig. 5, among the severely ill SFTS patients, another 25 patients also had oropharyngeal bleeding and positive T-SFTSV, they were received oxygen inhalation through masks, HCWs wore gloves and surgical mask with face shield in direct contact to them. Twenty-two patients with positive T-SFTSV received extensive cardiopulmonary resuscitation, HCWs have worn gloves, medical surgical masks with face shield in participation of cardiopulmonary resuscitation of these patients. Eleven patients with positive T-SFTSV were performed orotracheal intubation, disposable hat, latex gloves, medical protective mask with face shield were applied in HCWs in participation of orotracheal intubation. The ward environment was disinfected with 1000mg/L chlorine and ultraviolet radiation for more than 30 minutes after the severely ill patient was discharged. No human-to-human transmission incidents occurred again by precaution measures applied. SFTSV: severe fever with thrombocytopenia syndrome virus Figure 5 Diagram flow of personal protective equipment used in healthcare workers in this research Discussion Severe fever with thrombocytopenia syndrome is transmitted predominantly by tick bites and potentially human-to-human. Nosocomial and intrafamily transmission of SFTSV have been reported through contact with blood and secretions from patients [ 15 – 33 ], which put the health-care workers and close family members involved inpatient care at risk for exposure. Transmission of SFTSV during aerosol-generating medical procedures was also proposed as possible [ 15 , 16 , 19 , 28 , 36 , 37 ]. Therefore, standard barrier nursing methods are suggested as sufficient to prevent the transmission of SFTS in the current patient care setting, whereas the specific PPEs use and the effect on viral transmission have rarely been reported. A nosocomial SFTSV infection via human-to-human transmission occurred in our hospital [ 14 ], which has prompted the study on precaution measures against human-to-human transmission of SFTSV. Besides, this is the first analysis about SFTSV RNA shedding level from organs connected to the outside by relatively large samples. Human-to-human events of SFTSV have attracted urgent public health concern [ 15 – 33 ]. Research about SFTSV excretion from patient's body and PPEs application of HCWs against human-to-human transmission was sparsely investigated. In three case reports, it has been demonstrated that SFTSV was detected not only in blood but also in sputum, gastric juice, urine, semen and cerebrospinal fluid [ 38 – 40 ]. In the present study, our findings indicated SFTSV could shed out from respiratory tract, digestive tract and urinary tract of severely ill patients who have high viral load in blood, especially simultaneous shedding from fatal patients. Oropharyngeal virus shedding level was relatively higher than that from stool and urine. According to Bae et al, 28.8% of HCWs were infected SFTSV by contact with the severely ill SFTS patient, participation in administration of cardiopulmonary resuscitation, exposure to the patient’s body fluids and shorter individual hospital work experience were confirmed to be risk factors for SFTSV human-to-human. This study has underlined the importance of wearing appropriate personal protective equipment in treatment areas to SFTS patient [ 33 ]. Pharyngeal virus shedding may be a risk for SFTSV human-to-human of HCWs in conducting treatment of orotracheal intubation and cardiopulmonary resuscitation. In our research, there were 22 critical ill patients who received cardiopulmonary resuscitation, oropharyngeal virus shedding were found among them. To avoid human-to-human transmission incident, HCWs have worn gloves, medical surgical masks with face shield in participation of CPR among the 22 critical ill patients. Of note, we found that SFTSV was detected in bedside environment of two fatal patients with high viral load. This was consistent with a previous report, which demonstrated that positive SFTSV was detected in 14 (21%) of 67 swab samples from stethoscopes, doorknobs, television monitors and sink bed guardrails in five rooms of critically ill patients including 3 fatal cases. It was mentioned that television monitors and sink tables were remote from the patients without daily cleaning and disinfection, it's been speculated that aerosolized virus particles due to oral cavity/tracheal suction during ventilator application could reach areas remote from the patient [ 36 ]. Therefore, the research emphasized the importance of strict contact precautions and appropriate disinfecting procedures in the rooms of SFTS patients[ 36 ]. Besides, a recent study have reported that SFTSV aerosols at a certain concentration in a confined space could infect mice through the nose, mouth and ocular membranes [ 37 ]. Oropharyngeal virus shedding may contribute to the generation of aerosolized SFTSV particles through sputum aspiration or tracheal intubation. Furthermore, aerosol human-to-human transmission events of SFTSV have been reported both in China and Korea. In our research, disposable hat, latex gloves, medical protective mask with face shield were applied in HCWs in participation of orotracheal intubation for patients with oropharyngeal virus shedding against aerosol human-to-human transmission. No human-to-human infection events occurred after the PPEs application in this research. We recommended aerosol and droplet precautions are for healthcare workers and caregiving family members exposed to critically ill SFTS patients. To reduce the spread of virus aerosols in critically ill patients with oral or nasal bleeding, mask oxygen inhalation was suggested. Our research firstly report that positive SFTSV in respiratory, digestive and urinary tracts were associated with occurrence of complications and increased risk of death. SFTSV infection can elicit damage to multiple organ systems including lung. It was reported that lung imaging abnormalities was present in 29 to 68.1% of SFTS patients [ 41 ]. Pulmonary infection was associated with fatality or increased disease course in SFTS patients [ 42 ]. In the present study, SFTSV positive rate of throat swabs in the patients complicating pneumonia were significantly higher than patients without pneumonia. In addition, we found that throat swab SFTSV RNA was associated with developing fatal outcome. To our knowledge, this was the first report regarding contribution of SFTSV in respiratory tract to occurrence of complicating pneumonia. Pneumonia with mucosal damage, coughing and hemoptysis may aid in virus excretion of SFTS patients. We concluded that detection of oropharyngeal airway SFTSV might be useful to targeted making protective measures, predict pneumonia and disease severity of SFTS patients. SFTSV can cause gastrointestinal symptoms as diarrhea, nausea/vomiting, anorexia, and abdominal pain, the occurrence of gastrointestinal symptoms at the disease onset are favorably associated with a severe condition [ 43 ]. In this study, we found that SFTSV RNA in fecal/ anal swabs of SFTS patients was associated with diarrhea incident, SFTSV RNA levels in fecal/ anal swab was dependent on virus levels in patient's blood. Acute kidney injury was confirmed as a predictive biomarker for disease severity and poor prognosis [ 44 ]. In the current study, the incidence of AKI was 39.2%, higher than previous reports [ 44 , 45 ]. We confirmed that U-SFTSV in SFTS patients was significantly associated with incidence of AKI, which is in consistent with previous reports[ 44 ]. U-SFTSV evaluation can be useful for early diagnosis of AKI in SFTS patients according to this research. Virus shedding from the urine need to be vigilant, however, further research is needed on virus activity and infectivity. Our study has a few limitations. Firstly, lower limit of virus detection was 1000 copies/mL, viral load < 1000 copies/mL was undetectable, but it may be meaningless to outcome. Secondly, we did not perform virus cultures from environmental samples, further studies are needed on whether viable virus is detected on inanimate surfaces to elucidate the role of environmental contamination as a route of transmission. In conclusion, our research revealed that SFTSV could shed out from the upper respiratory tract, digestive tract and urinary tract from severely ill patients, SFTSV contamination was present in the surrounding environment in severe SFTS patients' rooms. Aerosol and droplet precautions are recommended for healthcare workers in participation of orotracheal intubation or oro/nasopharyngeal suction for severely ill SFTS patients with hemorrhagic signs. Our findings also suggested that SFTSV shedding from the upper respiratory tract, feces and urine were predictors for disease severity and poor outcome. Declarations Author contributions Li-Fen Hu, Wei Liu and Jia-Bin Li: performed conception and design of the study. Ting-Ting Bian, Qiang Chen, Meng-Yu Liu, Jia-Jia Li, Qin-Xiang Kong, Jian-Kang Zhang, Jin Wu, Jun Cheng, Yan-Qin Qiu, Rui Yu, Yufeng Gao, Guo-Sheng Chen, Ying Ye: performed experiments, collected and analysed data. Li-Fen Hu, Ting Wu, Wei Liu and Jia-Bin Li: analysed data, drafted the manuscript and figures, and revised the discussion. Funding This study was supported by the National Natural Science Foundation of China (82370016), the Key Research and Development planning project of Anhui Province (2022e07020043), the Health Research planning project of Anhui Province (AHWJ2022a018), the first affiliated hospital Clinical Research Project of Anhui Medical University (LCYJ2021YB005) and the Anhui Medical University Research Fund Project (2022xkj168). Conflict of interest We declare no competing interests. Ethical approval The study was approved by the Human Ethics Committee of Anhui Medical University (20200980). Informed consent was obtained from all patients, in accordance with the Declaration of Helsinki. References Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, et al. Fever with thrombocytopenia associated with a novel bunyavirus in china. 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Risk factors for person-to-person transmission of severe fever with thrombocytopenia syndrome. Infect Control Hosp Epidemiol. 2021;42(5):582–5. https://doi.org/10.1017/ice.2020.1258 Fang X, Hu J, Peng Z, Dai Q, Liu W, Liang S, et al. Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome bunyavirus human-to-human transmission. Plos Negl Trop Dis. 2021;15(4):e9037. https://doi.org/10.1371/journal.pntd.0009037 Wu YX, Yang X, Leng Y, Li JC, Yuan L, Wang Z, et al. Human-to-human transmission of severe fever with thrombocytopenia syndrome virus through potential ocular exposure to infectious blood. Int J Infect Dis. 2022;123:80–3. https://doi.org/10.1016/j.ijid.2022.08.008 Bae S, Chang HH, Kim SW, Kim Y, Wang E, Kim CK, et al. Nosocomial outbreak of severe fever with thrombocytopenia syndrome among healthcare workers in a single hospital in daegu, korea. Int J Infect Dis. 2022;119:95–101. https://doi.org/10.1016/j.ijid.2022.03.048 Ministry of Health of the People’s Republic of China. Guidelines for the prevention and treatment of fever with thrombocytopenia syndrome (2010 Edition). Chin J Clin Infect Dis 4, 2011; 193–194(in Chinese) Li Z, Cui L, Zhou M, Qi X, Bao C, Hu J, et al. Development and application of a one-step real-time rt-pcr using a minor-groove-binding probe for the detection of a novel bunyavirus in clinical specimens. J Med Virol. 2013;85(2):370–7. https://doi.org/10.1002/jmv.23415 Ryu BH, Kim JY, Kim T, Kim MC, Kim MJ, Chong YP, et al. Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms. Clin Microbiol Infect. 2018;24(8):911. https://doi.org/10.1016/j.cmi.2018.01.005 Wei X, Li S, Lu Y, Qiu L, Xu N, Guo X, et al. Severe fever with thrombocytopenia syndrome virus aerosol infection in c57/bl6 mice. Virology. 2023;581:58–62. https://doi.org/10.1016/j.virol.2023.03.001 Akagi K, Miyazaki T, Oshima K, Umemura A, Shimada S, Morita K, et al. Detection of viral rna in diverse body fluids in an sfts patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review. Bmc Infect Dis. 2020;20(1):281. https://doi.org/10.1186/s12879-020-05012-8 Koga S, Takazono T, Ando T, Hayasaka D, Tashiro M, Saijo T, et al. Severe fever with thrombocytopenia syndrome virus rna in semen, japan. Emerg Infect Dis. 2019;25(11):2127–8. https://doi.org/10.3201/eid2511.190061 Jeong EJ, Song JY, Lim CS, Lee I, Park MS, Choi MJ, et al. Viral shedding from diverse body fluids in a patient with severe fever with thrombocytopenia syndrome. J Clin Virol. 2016;80:33–5. https://doi.org/10.1016/j.jcv.2016.04.018 Ashizawa H, Yamamoto K, Ashizawa N, Takeda K, Iwanaga N, Takazono T, et al. Associations between chest ct abnormalities and clinical features in patients with the severe fever with thrombocytopenia syndrome. Viruses. 2022;14(2). https://doi.org/10.3390/v14020279 Zuo Y, Wang H, Huang J, Zhang F, Lv D, Meng T, et al. Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: a multicentre observational study. J Med Virol. 2023;95(4):e28712. https://doi.org/10.1002/jmv.28712 Li H, Lu QB, Xing B, Zhang SF, 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. Lancet Infect Dis. 2018;18(10):1127–37. https://doi.org/10.1016/S1473-3099(18)30293-7 Zhang Q, Zhao J, Dai Y, Jiang Z, Chen T, Hu N, et al. A high viral load in urine correlates with acute kidney injury and poor outcomes in hospitalized patients with severe fever with thrombocytopenia syndrome: a noninvasive and convenient prognostic marker. Open Forum Infect Dis. 2023;10(4):ofad85. https://doi.org/10.1093/ofid/ofad085 He F, Zheng X, Zhang Z. Clinical features of severe fever with thrombocytopenia syndrome and analysis of risk factors for mortality. Bmc Infect Dis. 2021;21(1):1253. https://doi.org/10.1186/s12879-021-06946-3 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3873036\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":267942766,\"identity\":\"8d4509a7-aed7-4bc0-9bed-ac55dda3347c\",\"order_by\":0,\"name\":\"Li-Fen Hu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Li-Fen\",\"middleName\":\"\",\"lastName\":\"Hu\",\"suffix\":\"\"},{\"id\":267942767,\"identity\":\"6bd5e499-8351-4f7f-bfb0-5e9b84ba8d51\",\"order_by\":1,\"name\":\"Ting-Ting Bian\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ting-Ting\",\"middleName\":\"\",\"lastName\":\"Bian\",\"suffix\":\"\"},{\"id\":267942768,\"identity\":\"0aad8fa6-8b87-462d-87e3-85f5c93bdc8e\",\"order_by\":2,\"name\":\"Qiang Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qiang\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":267942769,\"identity\":\"0d62044a-21f5-4bcd-9a86-7d756f58b343\",\"order_by\":3,\"name\":\"Meng-Yu Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical 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University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rui\",\"middleName\":\"\",\"lastName\":\"Yu\",\"suffix\":\"\"},{\"id\":267942776,\"identity\":\"9cf9dfa7-3471-4aab-99f7-1a833a63145c\",\"order_by\":10,\"name\":\"Yan-Qin Qiu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yan-Qin\",\"middleName\":\"\",\"lastName\":\"Qiu\",\"suffix\":\"\"},{\"id\":267942777,\"identity\":\"6fcb7272-2d6e-4f35-b521-53bfc1ea3d9a\",\"order_by\":11,\"name\":\"Yu-Feng Gao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu-Feng\",\"middleName\":\"\",\"lastName\":\"Gao\",\"suffix\":\"\"},{\"id\":267942778,\"identity\":\"ab0eb380-4973-4ad4-af5d-0d82c9bdb3a3\",\"order_by\":12,\"name\":\"Guo-Sheng Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Guo-Sheng\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":267942779,\"identity\":\"384c141d-e82d-48ae-a82b-88c6ca5f8030\",\"order_by\":13,\"name\":\"Ying Ye\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ying\",\"middleName\":\"\",\"lastName\":\"Ye\",\"suffix\":\"\"},{\"id\":267942780,\"identity\":\"026e193d-ec69-49d7-bc92-b7684a7c5204\",\"order_by\":14,\"name\":\"Ting Wu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical 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Li\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACPmaGhAOMDRIM/Aw8YAHGBkJa2GBaJBuI1gJTZnCAaC3sDA8P/NxhkWd8/OzRzTwMNrIbDjA/e0DIYQd7z0gUm53JS7vNw5BmvOEAm7kBQb/wtkkkbjuQYwbUcjhxwwEeNgmCtvwFatnc/wak5T9xWg6DbNkgAbblAJFaZM9IJM648cbs5hyDZOOZh9nM8Grh5z+T/PHtjrrE/v4csxtvKuxk+443P8OrhYGBJwGJAwoqZvzqgYD9AEElo2AUjIJRMMIBAGCGSXdOesyEAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Anhui Medical University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Jia-Bin\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-01-17 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SFTSV: severe fever with thrombocytopenia syndrome virus.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCorrelations of SFTSV load in blood with throat swabs, anal swabs and urine in patients with severe fever with thrombocytopenia syndrome\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/7ef5e2d69cfc8181906f3e0d.png\"},{\"id\":49895232,\"identity\":\"345cdd17-0ac6-4419-9fcf-7566859e16d3\",\"added_by\":\"auto\",\"created_at\":\"2024-01-19 21:40:00\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":1959095,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eSFTSV shedding pattern from severely ill patients with severe fever with thrombocytopenia syndrome\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/d8c7333531f36aec6072f2e8.png\"},{\"id\":49895233,\"identity\":\"35f4778f-729e-408a-8d5a-a9f1bfd80a01\",\"added_by\":\"auto\",\"created_at\":\"2024-01-19 21:40:00\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":68010,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e\\n\\u003cp\\u003eAKI: Acute kidney injury\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCorrelations between comorbidities and SFTSV distribution in severely ill patients with severe fever with thrombocytopenia syndrome\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/c8f01320739e43b8f6181485.png\"},{\"id\":49895235,\"identity\":\"ddd1a70e-e98b-470a-992d-8f89a0f1aebd\",\"added_by\":\"auto\",\"created_at\":\"2024-01-19 21:40:00\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":74160,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDifference\\u003c/strong\\u003e \\u003cstrong\\u003eof SFTSV distribution between death group and non-death group in severe ill SFTS patients\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/8f065447a0ad19e5924168f3.png\"},{\"id\":49896086,\"identity\":\"1783afe2-3c6f-457c-a709-712a5bc5f47e\",\"added_by\":\"auto\",\"created_at\":\"2024-01-19 21:48:01\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":45199,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDiagram flow of personal protective equipment used in healthcare workers in this research\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/7d0c06cdfcb36558de595a0a.png\"},{\"id\":50651235,\"identity\":\"bd4b290d-0ab9-4f7c-a447-1e35cf345fcf\",\"added_by\":\"auto\",\"created_at\":\"2024-02-05 09:13:45\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1535255,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3873036/v1/b5c76fd4-8f44-4678-9075-a42c44932278.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients:A Prospective, Multicenter Study\",\"fulltext\":[{\"header\":\"Intruduction\",\"content\":\"\\u003cp\\u003eSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by SFTS virus (SFTSV) belonging to Bunyavirales order, Pheniviridae family, Bandavirus genus [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e], which was renamed as \\u003cem\\u003eDabie bandavirus\\u003c/em\\u003e (DBV) by the International Committee on Taxonomy of Viruses in 2019 [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. In recent years, SFTS has been rapidly spreading in Asia including China, Japan, South Korea, Vietnam, Pakistan, and Myanmar [\\u003cspan additionalcitationids=\\\"CR4 CR5 CR6 CR7\\\" citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. The public health concern of SFTSV is primarily posed by the wide distribution of its vectors (ticks) and the broad spectrum of its hosts [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. \\u003cem\\u003eHaemaphysalis longicornis\\u003c/em\\u003e (\\u003cem\\u003eH. longicornis\\u003c/em\\u003e) tick is the main reservoir and vector of SFTSV, which although native to East Asia, has established populations in the Australasian and Western Pacific Regions [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Although most persons with SFTS experience nonspecific influenza-like symptoms, more severe and prolonged disease can occur in severe ill patients. Severe infection is associated with high-grade viremia and excessive inflammatory response, further leading to organ damage, nervous system disorders, blood clotting abnormalities, and secondary infection in severe patient. The case fatality rate of critically ill patients is up to 10%-50% [\\u003cspan additionalcitationids=\\\"CR11 CR12\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. Due to its high fatality and the possibility of causing pandemic transmission, SFTS was listed among the top 10 priority infectious disease with urgent need for research by the World Health Organization in 2017 [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe SFTSV infection was primarily transmitted from infected tick to human. In addition to tick transmission, human-to-human transmission of SFTS had been widely reported and mostly caused by unprotected exposure to individuals with SFTS disease [\\u003cspan additionalcitationids=\\\"CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. A strong risk factor linked to human-to-human SFTSV spread is contact with infected bodily fluids. However, there is still a dearth of knowledge regarding the infection routes and related factors that might affect the human-to-human transmission of SFTSV without a comprehensive evaluation of the viral shedding pattern. Research on specific precaution measures against SFTSV human-to-human transmission infection are becoming impending demand.\\u003c/p\\u003e \\u003cp\\u003eIn the present prospective multicenter study, SFTSV shedding pattern from organs connected to the outside in severely ill patients were evaluated. Precaution measures were applied for healthcare workers (HCWs) exposed to critically ill SFTS patients. The relationship between virus distribution with comorbidities of patients and human-to-human transmission events were analyzed. The result would be important for effective control strategies against SFTSV human-to-human transmission.\\u003c/p\\u003e\"},{\"header\":\"Materials and Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Design and Participants\\u003c/h2\\u003e \\u003cp\\u003eA multicenter cohort study was performed in three sentinel hospitals for SFTS in Anhui province, including the First Affiliated Hospital of Anhui Medical University, the Chaohu Affiliated Hospital of Anhui Medical University and Lu'an People's Hospital of Anhui Medical University from April 2020 to October 2022. We enrolled patients (\\u0026ge;\\u0026thinsp;18 years and \\u0026lt;\\u0026thinsp;80 years of age) who were hospitalized and confirmed as SFTSV infection by positive polymerase-chain reaction (PCR) detection of blood samples. Patients of younger than 18 years old, with chronic respiratory disease, gastrointestinal diseases and chronic kidney disease were excluded. According to the guidelines for the prevention and treatment of fever with thrombocytopenia syndrome by a standard criterion released by the Chinese Ministry of Health[\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e], patients were diagnosed as having mild illness, severe or critical ill form of disease. All the SFTS patients were underwent chest radiography or chest computed tomography (CT) during the disease course. The study protocol was approved by the Human Ethics Committee of Anhui Medical University (20200980). Informed consent was obtained from all patients, in accordance with the Declaration of Helsinki.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eVirological Investigations\\u003c/h2\\u003e \\u003cp\\u003eSFTSV infection was confirmed in all patients by testing serum specimens with a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. At the stage of disease progression of patients, the blood, throat swab, anal swab, urine and bedside environment swab samples of the patients were collected for SFTSV detection. RNA was extracted from these samples using the high-purity viral RNA kit (Omega, Guangzhou, China) according to the manufacturer\\u0026rsquo;s instructions. SFTSV RNA was amplified using specific primers and probes by RT-PCR under conditions previously described using the SFTSV nucleic acid quantitative detection Kit (DaAn Gene Co, Guangzhou, China) [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e].\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePersonal protective equipment use of healthcare workers\\u003c/h2\\u003e \\u003cp\\u003eDifferent PPEs were applied in HCWs according to exposure risks. The single-use medical masks were used in HCWs contacting with mild SFTS patients. The gloves and surgical mask with face shield were used in HCWs exposed to SFTS patients with hemorrhagic manifestations and positive T-SFTSV. The gloves, surgical mask or medical protective mask and face shield were applied by HCWs participation in cardiopulmonary resuscitation (CPR). The disposable hat, latex gloves, medical protective mask with face shield were applied by HCWs in participation of orotracheal intubation for severely ill patients with positive T-SFTSV. Besides, mask oxygen inhalation was used in critically ill patients with bloody secretions of oral or nasal and positive T-SFTSV. The ward environment was disinfected with 1000mg/L chlorine and ultraviolet radiation for more than 30 minutes after the patient was discharged.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData collection of SFTS patients\\u003c/h2\\u003e \\u003cp\\u003eHospital-based data were collected during the hospitalization by using a standardized medical questionnaire. A medical record review was performed to collect information on epidemiologic, clinical manifestations, signs of haemorrhage and laboratory parameters. Personal protective equipment (PPE) use of HCWs and occurrence of SFTSV human-to-human event among the patients were also recorded.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eData were analyzed using SPSS, version 20.0 (SPSS Inc., USA). Quantitative variables were expressed as means\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) or as medians (interquartile range), categorical variables were expressed as the number (percentage). Student's t test was applied when normality assumptions were satisfied; otherwise, the equivalent non-parametric test was used. A chi-square test was used to examine the difference in the percentage of categorical variables. Graphpad prism 5 software was used to compare values in groups and calculate the correlation coefficients and significance values of two variables. The correlation analysis of Log10 (SFTSV) level in blood with that from other samples was calculated using the methods of the Pearson correlation coefficient. A two-sided \\u003cem\\u003ep\\u003c/em\\u003e-value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered statistically significant.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCharacteristics of Viral shedding from SFTS patients\\u003c/h2\\u003e \\u003cp\\u003eOne hundred and eighty-nine SFTS patients were included in the study, the median age was 62.5 years, 83 (43.9%) patients were male and 106 (56.1%) were female. Fifty-four patients died (case fatality rate, 28.57%). The median SFTSV load was 9.6 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL [interquartile range (IQR) 3.6x10\\u003csup\\u003e3\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;1.6 x10\\u003csup\\u003e4\\u003c/sup\\u003e] in blood (B-SFTSV) in 23 mild patients, 8.3 x10\\u003csup\\u003e5\\u003c/sup\\u003e copies/mL [interquartile range (IQR) 1x10\\u003csup\\u003e5\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;5.2 x10\\u003csup\\u003e6\\u003c/sup\\u003e] in blood (B-SFTSV) in 166 severely ill (\\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.001). Positive SFTSV in throat swabs (T-SFTSV) were detected in 121 (64.02%) severely ill patients with median load 2.1 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL (IQR 1.2x10\\u003csup\\u003e3\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;8.1 x10\\u003csup\\u003e3\\u003c/sup\\u003e). Positive SFTSV in fecal /anal swabs (F-SFTSV) were detected in 91 (48.15%) severely ill patients with median load 1.3 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL (IQR 1.0x10\\u003csup\\u003e3\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;3.0 x10\\u003csup\\u003e3\\u003c/sup\\u003e). Positive SFTSV in urine (U-SFTSV) were detected in 65 (34.4%) severely ill patients with median load 1.5 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL (IQR 1.0x10\\u003csup\\u003e3\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;2.8 x10\\u003csup\\u003e3\\u003c/sup\\u003e). No positive T-SFTSV, F-SFTSV and U-SFTSV were detected in 23 mild SFTS patients.\\u003c/p\\u003e \\u003cp\\u003eThe viral load of blood samples (N\\u0026thinsp;=\\u0026thinsp;121) is significantly higher than those of throat swabs (N\\u0026thinsp;=\\u0026thinsp;121), anal swabs (N\\u0026thinsp;=\\u0026thinsp;91) and urine (N\\u0026thinsp;=\\u0026thinsp;65) (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001), the viral load of throat swabs is significantly higher than that of anal swabs (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001) (Fig.\\u0026nbsp;1). The results showed positive correlations of SFTSV levels in blood with throat swabs (r\\u0026thinsp;=\\u0026thinsp;0.4535, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001), anal swabs (r\\u0026thinsp;=\\u0026thinsp;0.3263, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.0016), and urine (r\\u0026thinsp;=\\u0026thinsp;0.4102, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.0007), respectively (Fig.\\u0026nbsp;1). It is noteworthy that positive SFTSV of bedside environment swab was detected in two fatal patients with pneumonia, besides, one had oral hemorrhage, the other one had cough and expectoration. Our research demonstrated SFTSV could shed out not only the blood, but from oropharynx, feces and urine in severely ill patients with high viral load (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eA: Comparison of SFTSV levels from different samples; B: Correlations of SFTSV levels in blood with throat swabs; C: Correlations of SFTSV levels in blood with anal swabs; D: Correlations of SFTSV levels in blood with urine; The viral levels were in the format of Log10 viral RNA copies/mL. ***\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001. SFTSV: severe fever with thrombocytopenia syndrome virus.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eFigure\\u0026nbsp;1 Correlations of SFTSV load in blood with throat swabs, anal swabs and urine in patients with severe fever with thrombocytopenia syndrome\\u003c/b\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCorrelations between clinical phenotypes and SFTSV distribution in patients\\u003c/h2\\u003e \\u003cp\\u003ePneumonia occurred in 73 (60.3%) patients with positve-SFTSV in throat swabs, significantly higher than in 13 (19.1%) patients with negative-SFTSV in throat swabs (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). Diarrhea occurred in 69 (75.8%) patients with positve-SFTSV in anal swabs, in 42 (42.8%) patients with negative-SFTSV in anal swabs (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). Acute kidney injury (AKI) occurred in 61 (93.8%) patients with positve-SFTSV in urine, in 13 (7.7%) patients with negative-SFTSV in urine (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001)(Fig.\\u0026nbsp;3). The levels of estimated glomerular filtration rate (eGFR) in patients with SFTSV in urine were significantly lower than that in negative-SFTSV urine group (52.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.8 \\u003cem\\u003evs\\u003c/em\\u003e 91.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;22.2, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001).\\u003c/p\\u003e \\u003cp\\u003eAmong the 166 severely ill patients, 43 patients had cough, 13 patients had hemoptysis and 26 patients had oropharyngeal bleeding. All the patients with cough and oral or nasal bleeding had positive SFTSV of throat swabs, which is significantly higher than the patients without these presence.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e \\u003cp\\u003eAKI: Acute kidney injury\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eFigure\\u0026nbsp;3 Correlations between comorbidities and SFTSV distribution in severely ill patients with severe fever with thrombocytopenia syndrome\\u003c/b\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCorrelation between case fatality rate and SFTSV distribution in patients\\u003c/h2\\u003e \\u003cp\\u003eAmong 54 patients who developed fatal outcome, the median SFTSV load was 7.2 x10\\u003csup\\u003e6\\u003c/sup\\u003e copies/mL [interquartile range (IQR) 1.6x10\\u003csup\\u003e6\\u003c/sup\\u003e \\u0026minus;\\u0026thinsp;3.2 x10\\u003csup\\u003e7\\u003c/sup\\u003e] in blood (B-SFTSV). Positive SFTSV detection was determined in all (54) of throat swabs, 88.89% (48/54) of anal swabs, 79.63% ( 43/54) of the urine samples, all significantly higher than the positive rate obtained from the non-fatal cases (0%, 31.85% and 16.29%, respectively, all \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) (Fig.\\u0026nbsp;4). Among 61 patients who had simultaneously positive results in all throat swabs, anal swabs and urine samples, 43 fatal patients had positive SFTSV for all sample types, which is significantly higher than the survived patients.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eFigure\\u0026nbsp;4 Difference of SFTSV distribution between death group and non-death group in severe ill SFTS patients\\u003c/b\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePrecaution measures and incidence of SFTSV human-to-human transmission\\u003c/h2\\u003e \\u003cp\\u003eIn this research, a human-to-human transmission was identified with altogether 7 patients involved. The index case had SFTSV load of 9 x10\\u003csup\\u003e6\\u003c/sup\\u003e copies/mL in plasma sample, 1.2 x10\\u003csup\\u003e5\\u003c/sup\\u003e copies/mL in the throat swab, 2.4 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL in the anal swab, and 2.2 x10\\u003csup\\u003e3\\u003c/sup\\u003e copies/mL in urine. Among the eight persons exposure to the hemorrhagic patient with cardiopulmonary resuscitation (CPR) and orotracheal intubation bleeding, six persons were infected without tick exposure history. None of the six infected patients worn face shield as personal protective equipment. By contrast, two HCWs who had close contact with the index case including sputum suction and bleeding treatment were all samples test negative for SFTSV, one had worn double surgical masks with face shield, the other one wearing N95 mask in cardiopulmonary resuscitation (CPR) for more than 1 hour.\\u003c/p\\u003e \\u003cp\\u003eAs in Fig.\\u0026nbsp;5, among the severely ill SFTS patients, another 25 patients also had oropharyngeal bleeding and positive T-SFTSV, they were received oxygen inhalation through masks, HCWs wore gloves and surgical mask with face shield in direct contact to them. Twenty-two patients with positive T-SFTSV received extensive cardiopulmonary resuscitation, HCWs have worn gloves, medical surgical masks with face shield in participation of cardiopulmonary resuscitation of these patients. Eleven patients with positive T-SFTSV were performed orotracheal intubation, disposable hat, latex gloves, medical protective mask with face shield were applied in HCWs in participation of orotracheal intubation. The ward environment was disinfected with 1000mg/L chlorine and ultraviolet radiation for more than 30 minutes after the severely ill patient was discharged. No human-to-human transmission incidents occurred again by precaution measures applied.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eSFTSV: severe fever with thrombocytopenia syndrome virus\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eFigure\\u0026nbsp;5 Diagram flow of personal protective equipment used in healthcare workers in this research\\u003c/b\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eSevere fever with thrombocytopenia syndrome is transmitted predominantly by tick bites and potentially human-to-human. Nosocomial and intrafamily transmission of SFTSV have been reported through contact with blood and secretions from patients [\\u003cspan additionalcitationids=\\\"CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e], which put the health-care workers and close family members involved inpatient care at risk for exposure. Transmission of SFTSV during aerosol-generating medical procedures was also proposed as possible [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e]. Therefore, standard barrier nursing methods are suggested as sufficient to prevent the transmission of SFTS in the current patient care setting, whereas the specific PPEs use and the effect on viral transmission have rarely been reported. A nosocomial SFTSV infection via human-to-human transmission occurred in our hospital [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e], which has prompted the study on precaution measures against human-to-human transmission of SFTSV. Besides, this is the first analysis about SFTSV RNA shedding level from organs connected to the outside by relatively large samples.\\u003c/p\\u003e \\u003cp\\u003eHuman-to-human events of SFTSV have attracted urgent public health concern [\\u003cspan additionalcitationids=\\\"CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. Research about SFTSV excretion from patient's body and PPEs application of HCWs against human-to-human transmission was sparsely investigated. In three case reports, it has been demonstrated that SFTSV was detected not only in blood but also in sputum, gastric juice, urine, semen and cerebrospinal fluid [\\u003cspan additionalcitationids=\\\"CR39\\\" citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e]. In the present study, our findings indicated SFTSV could shed out from respiratory tract, digestive tract and urinary tract of severely ill patients who have high viral load in blood, especially simultaneous shedding from fatal patients. Oropharyngeal virus shedding level was relatively higher than that from stool and urine. According to Bae et al, 28.8% of HCWs were infected SFTSV by contact with the severely ill SFTS patient, participation in administration of cardiopulmonary resuscitation, exposure to the patient\\u0026rsquo;s body fluids and shorter individual hospital work experience were confirmed to be risk factors for SFTSV human-to-human. This study has underlined the importance of wearing appropriate personal protective equipment in treatment areas to SFTS patient [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. Pharyngeal virus shedding may be a risk for SFTSV human-to-human of HCWs in conducting treatment of orotracheal intubation and cardiopulmonary resuscitation. In our research, there were 22 critical ill patients who received cardiopulmonary resuscitation, oropharyngeal virus shedding were found among them. To avoid human-to-human transmission incident, HCWs have worn gloves, medical surgical masks with face shield in participation of CPR among the 22 critical ill patients.\\u003c/p\\u003e \\u003cp\\u003eOf note, we found that SFTSV was detected in bedside environment of two fatal patients with high viral load. This was consistent with a previous report, which demonstrated that positive SFTSV was detected in 14 (21%) of 67 swab samples from stethoscopes, doorknobs, television monitors and sink bed guardrails in five rooms of critically ill patients including 3 fatal cases. It was mentioned that television monitors and sink tables were remote from the patients without daily cleaning and disinfection, it's been speculated that aerosolized virus particles due to oral cavity/tracheal suction during ventilator application could reach areas remote from the patient [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. Therefore, the research emphasized the importance of strict contact precautions and appropriate disinfecting procedures in the rooms of SFTS patients[\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. Besides, a recent study have reported that SFTSV aerosols at a certain concentration in a confined space could infect mice through the nose, mouth and ocular membranes [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e]. Oropharyngeal virus shedding may contribute to the generation of aerosolized SFTSV particles through sputum aspiration or tracheal intubation. Furthermore, aerosol human-to-human transmission events of SFTSV have been reported both in China and Korea. In our research, disposable hat, latex gloves, medical protective mask with face shield were applied in HCWs in participation of orotracheal intubation for patients with oropharyngeal virus shedding against aerosol human-to-human transmission. No human-to-human infection events occurred after the PPEs application in this research. We recommended aerosol and droplet precautions are for healthcare workers and caregiving family members exposed to critically ill SFTS patients. To reduce the spread of virus aerosols in critically ill patients with oral or nasal bleeding, mask oxygen inhalation was suggested.\\u003c/p\\u003e \\u003cp\\u003eOur research firstly report that positive SFTSV in respiratory, digestive and urinary tracts were associated with occurrence of complications and increased risk of death. SFTSV infection can elicit damage to multiple organ systems including lung. It was reported that lung imaging abnormalities was present in 29 to 68.1% of SFTS patients [\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e]. Pulmonary infection was associated with fatality or increased disease course in SFTS patients [\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e]. In the present study, SFTSV positive rate of throat swabs in the patients complicating pneumonia were significantly higher than patients without pneumonia. In addition, we found that throat swab SFTSV RNA was associated with developing fatal outcome. To our knowledge, this was the first report regarding contribution of SFTSV in respiratory tract to occurrence of complicating pneumonia. Pneumonia with mucosal damage, coughing and hemoptysis may aid in virus excretion of SFTS patients. We concluded that detection of oropharyngeal airway SFTSV might be useful to targeted making protective measures, predict pneumonia and disease severity of SFTS patients.\\u003c/p\\u003e \\u003cp\\u003eSFTSV can cause gastrointestinal symptoms as diarrhea, nausea/vomiting, anorexia, and abdominal pain, the occurrence of gastrointestinal symptoms at the disease onset are favorably associated with a severe condition [\\u003cspan citationid=\\\"CR43\\\" class=\\\"CitationRef\\\"\\u003e43\\u003c/span\\u003e]. In this study, we found that SFTSV RNA in fecal/ anal swabs of SFTS patients was associated with diarrhea incident, SFTSV RNA levels in fecal/ anal swab was dependent on virus levels in patient's blood. Acute kidney injury was confirmed as a predictive biomarker for disease severity and poor prognosis [\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e]. In the current study, the incidence of AKI was 39.2%, higher than previous reports [\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e]. We confirmed that U-SFTSV in SFTS patients was significantly associated with incidence of AKI, which is in consistent with previous reports[\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e]. U-SFTSV evaluation can be useful for early diagnosis of AKI in SFTS patients according to this research. Virus shedding from the urine need to be vigilant, however, further research is needed on virus activity and infectivity.\\u003c/p\\u003e \\u003cp\\u003eOur study has a few limitations. Firstly, lower limit of virus detection was 1000 copies/mL, viral load\\u0026thinsp;\\u0026lt;\\u0026thinsp;1000 copies/mL was undetectable, but it may be meaningless to outcome. Secondly, we did not perform virus cultures from environmental samples, further studies are needed on whether viable virus is detected on inanimate surfaces to elucidate the role of environmental contamination as a route of transmission.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, our research revealed that SFTSV could shed out from the upper respiratory tract, digestive tract and urinary tract from severely ill patients, SFTSV contamination was present in the surrounding environment in severe SFTS patients' rooms. Aerosol and droplet precautions are recommended for healthcare workers in participation of orotracheal intubation or oro/nasopharyngeal suction for severely ill SFTS patients with hemorrhagic signs. Our findings also suggested that SFTSV shedding from the upper respiratory tract, feces and urine were predictors for disease severity and poor outcome.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLi-Fen Hu, Wei Liu and Jia-Bin Li: performed conception and design of the study. Ting-Ting Bian, Qiang Chen, Meng-Yu Liu, Jia-Jia Li, Qin-Xiang Kong, Jian-Kang Zhang, Jin Wu, Jun Cheng,\\u0026nbsp;Yan-Qin Qiu,\\u0026nbsp;Rui Yu, Yufeng Gao, Guo-Sheng Chen, Ying Ye: performed experiments, collected and analysed data. Li-Fen Hu, Ting Wu, Wei Liu and Jia-Bin Li: analysed data, drafted the manuscript and figures, and revised the discussion.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was supported by the National Natural Science Foundation of China (82370016), the Key Research and Development planning project of Anhui Province (2022e07020043), the Health Research planning project of Anhui Province (AHWJ2022a018), the first affiliated hospital Clinical Research Project of Anhui Medical University (LCYJ2021YB005) and the Anhui Medical University Research Fund Project (2022xkj168).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthical approval\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was approved by the Human Ethics Committee of Anhui Medical University (20200980). 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Viral shedding from diverse body fluids in a patient with severe fever with thrombocytopenia syndrome. J Clin Virol. 2016;80:33\\u0026ndash;5. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.jcv.2016.04.018\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.jcv.2016.04.018\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAshizawa H, Yamamoto K, Ashizawa N, Takeda K, Iwanaga N, Takazono T, et al. Associations between chest ct abnormalities and clinical features in patients with the severe fever with thrombocytopenia syndrome. Viruses. 2022;14(2). \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.3390/v14020279\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/v14020279\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZuo Y, Wang H, Huang J, Zhang F, Lv D, Meng T, et al. Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: a multicentre observational study. J Med Virol. 2023;95(4):e28712. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1002/jmv.28712\\u003c/span\\u003e\\u003cspan address=\\\"10.1002/jmv.28712\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLi H, Lu QB, Xing B, Zhang SF, 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. Lancet Infect Dis. 2018;18(10):1127\\u0026ndash;37. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/S1473-3099(18)30293-7\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/S1473-3099(18)30293-7\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhang Q, Zhao J, Dai Y, Jiang Z, Chen T, Hu N, et al. A high viral load in urine correlates with acute kidney injury and poor outcomes in hospitalized patients with severe fever with thrombocytopenia syndrome: a noninvasive and convenient prognostic marker. Open Forum Infect Dis. 2023;10(4):ofad85. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1093/ofid/ofad085\\u003c/span\\u003e\\u003cspan address=\\\"10.1093/ofid/ofad085\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHe F, Zheng X, Zhang Z. Clinical features of severe fever with thrombocytopenia syndrome and analysis of risk factors for mortality. Bmc Infect Dis. 2021;21(1):1253. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1186/s12879-021-06946-3\\u003c/span\\u003e\\u003cspan address=\\\"10.1186/s12879-021-06946-3\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Severe fever with thrombocytopenia syndrome virus, Dabie bandavirus, Shedding, Precaution measures, Multicenter study, Human-to-human\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3873036/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3873036/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground.\\u003c/h2\\u003e \\u003cp\\u003eSevere fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported.\\u003c/p\\u003e\\u003ch2\\u003eMethods.\\u003c/h2\\u003e \\u003cp\\u003eA multicenter cohort study was performed to determine SFTS virus (SFTSV) level from blood, throat swabs, fecal/ anal swabs, urine and bedside environment swabs of SFTS patients by qRT-PCR. PPEs were applied in healthcare workers based on the pathway of SFTSV shedding and occurrence of hemorrhagic signs in patients.\\u003c/p\\u003e\\u003ch2\\u003eResults.\\u003c/h2\\u003e \\u003cp\\u003eA total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57%). Positive SFTSV in throat swabs (T-SFTSV), fecal /anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02%), 91 (48.15%) and 65 (34.4%) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs.\\u003c/p\\u003e\\u003ch2\\u003eConclusions.\\u003c/h2\\u003e \\u003cp\\u003eOur research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients:A Prospective, Multicenter Study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-01-19 21:39:56\",\"doi\":\"10.21203/rs.3.rs-3873036/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"ced6b591-982c-4f3a-8431-ba6e6162bbe1\",\"owner\":[],\"postedDate\":\"January 19th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-02-05T09:05:38+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-01-19 21:39:56\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-3873036\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3873036\",\"identity\":\"rs-3873036\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}