Introduction
Hemorrhagic fever with renal syndrome (HFRS) is predominantly attributed to Hantaan ortho-hantavirus (HTNV), a naturally occurring focal infectious disease primarily transmitted through the inherent host of rodents. HTNV was initially discovered in South Korea in 1978 and is prevalent in regions in China, South Korea, Russia, and Vietnam[1, 2]. The endemic strains in Northeast China encompass HTNV and Seoul virus (SEOV). Human infection occurs via exposure to wild mice’s blood, saliva, urine, and feces or through the transmission of vector organisms such as fleas settling on the exterior of wild mice. It has been reported that there were over 100,000 annual infection cases globally, with China being among the most severely affected countries, accounting for more than 90% of these infections[3]. The recognizable HFRS course is divided into five stages: fever, hypotensive shock, oliguria, polyuria, and recovery[1]. These disease stages are well-defined in severe HFRS, but the boundaries are not distinct or may overlap in mild and moderate cases[4]. During the initial phase of the disease, there are typically pronounced ”three pains”(headache, low back pain, orbital pain) and ”three reds”(face red, neck red, and chest red), but it is significantly relieved after the polyuria stage. Based on the severity of fever, toxic symptoms, bleeding, shock, and kidney damage, the clinical cases were divided into five categories: mild, moderate, severe, critical, and atypical, with a mortality rate ranging from 0.5% to 40%. The severity of the disease is also dependent on variants of virulent agents[5]. HFRS can be instigated by Hantaan ortho-hantavirus (HTNV), Seoul virus (SEOV), Dobrava-Belgrade virus (DOBV), and Puumala virus (PUUV). HTNV and DOBV frequently infect and cause severe HFRS, while SEOV mainly leads to moderate HFRS[1, 4]. Apart from clinical manifestations and epidemiological history, diagnosis relies on laboratory testing methods and techniques such as serology, polymerase chain reaction, immunochemistry, and virus culture.
Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) is an emergent viral hemorrhagic fever with a significant fatality rate. It was initially identified and documented in China in 2009 and was subsequently isolated and named as severe fever with thrombocytopenia syndrome (SFTS) in 2010, referred to as novel Bunyavirus[6]. It belongs to the family Bunyaviridae and the genus Phlebovirus. SFTS occurrences were primarily concentrated in East Asian countries such as China, Japan, South Korea, and Vietnam. It has been reported that the cumulative number of confirmed cases was 5360 in China by 2016, 866 in South Korea by 2018, and 467 in Japan by 2019, respectively[7]. The pathogen is predominantly transmitted through blood infection, and tick-to-human transmission is the main route of human infection, with Haemaphysalis longicornis being the most common transmission vector. The infection manifests as severe fever, platelet and leukopenia, obvious neurological symptoms, and gastrointestinal symptoms with high mortality.
The various hemorrhagic fevers (HFRS and SFTS) demonstrate similar epidemic characteristics and clinical symptoms. Regarding epidemiological characteristics, spatial and temporal distribution mirror the attributes of susceptible populations. Meanwhile, the clinical characteristics are similar in the early stage of the disease, such as general discomfort, abrupt onset of fever, and irregular coagulation function[8]. Despite overlapping similarities in clinical features, instances of co-infection with both viruses are extremely rare.
Liaoning Province is recognized as a high-prevalence area for HFRS and SFTS, exhibiting a recent upward trend. Additionally, the incidence rate of SFTS persistently escalates, engendering significant public health problems. The epidemic zones are mainly distributed in Dandong, Dalian, Benxi, and other parts of Liaodong, particularly Fengcheng City and Kuandian County, which are under the jurisdiction of Dandong. At the same time, there exists considerable overlap between the endemic areas and the vector dispersion. Liaoning Province harbors high tick density, increasing the risk for humans and animals. Consequently, Liaoning Province provides an ideal research environment for investigating diseases.
It is an important scientific question of effectively diagnosing viral hemorrhagic fevers with similar characteristics. Presently, most studies independently study analyze the clinical characteristics and diagnostic methods of the two viral hemorrhagic fevers in isolation or establish diagnostic models rooted in clinical prediction and identification, failing to comprehensively combine clinical data and specimens for a thorough analysis of the correlation between the two viral hemorrhagic fevers. Besides, some research on HFRS mainly consist of descriptive studies on case reports, nursing experience, and clinical characteristics, with minimal studies on severe HFRS[9, 10]. Therefore, utilizing clinical data and combining it with the detection of patient samples, this study conducted the statistical analysis of severe cases of HFRS and explored the relationship between co-infection and disease severity combined with laboratory detection.
The present study collected the clinical case information and blood specimens of 22 patients clinically diagnosed with HFRS admitted to Dandong Infectious Diseases Hospital of Liaoning Province from December 2021 to October 2022 in Northeast China, where two types of infectious diseases are highly endemic. These cases were categorized into severe and non-severe groups. Statistical description and inference were applied to compare and analyze the clinical characteristic differences between the two groups. Meanwhile, molecular biological detection of common vector infectious disease pathogens was carried out on the blood samples of patients, molecular biological detection of their cell cultures was carried out, and the pathogens were isolated. The severity of HFRS was identified under different factors. Moreover, the co-infection of HFRS and SFTS was also discussed to provide scientific reference for the early and timely differential diagnosis, effective prevention, and treatment of severe cases.