Hematological Findings among COVID-19 Patients Attending King Khalid Hospital at Najran, Kingdom of Saudi Arabia.

COVID-19 is a global pandemic viral infection that has affected millions worldwide. Limited data is available on the effect of COVID-19 on hematological parameters in Saudi Arabia. This study is aimed at examining the role of hematological parameters among COVID-19 patients admitted to King Khalid Hospital in Najran, Saudi Arabia. This is a retrospective, hospital-based study of 514 cases who were recruited during August to October 2020. 257 COVID-19 patients formed the study group, and a further 257 negative subjects formed the control group. Anemia was significantly elevated in positive subjects over controls (respectively, 64.2% and 35.8%), with patients 2.5 times more likely to be anemic (p < 0.01). Thrombocytopenia was higher in patients over controls (respectively, 62% and 38%), with patients ~1.7 times more likely to be thrombocytopenic (p < 0.01). Moreover, leukopenia was significantly higher in patients over controls (respectively, 71% and 29%), with positive subjects ~2.6 times more likely to be leukopenic. Our study results indicate that mild anemia associated with leukopenia may have diagnostic value for COVID-19. Careful assessment of hematological parameters, at baseline and throughout the disease path, will assist physicians in formulating personalized approaches to treatment and promptly offer intensive care to those in greater need.

COVID-19 associated symmetrical peripheral gangrene: A case series.

BACKGROUND AND AIMS: The novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has turned the world topsy-turvy since its onset in 2019. The thromboinflammatory complications of this disease are common in critically ill patients and associated with poor prognosis. Symmetrical peripheral gangrene (SPG) is characterized by symmetrical distal gangrene in absence of any large vessel occlusion or vasculitis and it is usually associated with critical illness. Our aim was to report the clinical profile and outcome of patients diagnosed with SPG associated with COVID-19. To the best of our knowledge, no such similar cases have been reported till date. METHODS: In this case series, we have discussed the clinical presentation, laboratory parameters and outcome in a series of two patients of SPG associated with COVID-19 and also compared those findings. Due to paucity of data, we also reviewed the literature on this under-diagnosed and rarely reported condition and association. RESULTS: Two consecutive patients (both males, age range: 37-42 years, mean: 39.5 years) were admitted with the diagnosis of COVID-19 associated SPG. Both patients had clinical and laboratory evidence of disseminated intravascular coagulation (DIC). Leucopenia was noted in both patients. Despite vigorous therapy, both patients succumbed to their illness within a fortnight of admission. CONCLUSION: SPG in the background of COVID-19 portends a fatal outcome. Physicians should be aware of its grim prognosis.

Effect of the coronavirus pandemic on tumor markers.

The new type of coronavirus could cause severe acute respiratory syndrome and injuries in other systems as well. Multiple organ damage can occur rapidly in patients infected with coronavirus disease 2019 (COVID-19). Previous studies have shown that many laboratory biomarkers were not within the normal ranges in COVID-19 patients. We aimed to summarize laboratory parameters and the tumor markers in COVID-19 patients. This is a retrospective cohort study conducted on 53 women between the ages of 19-85 years infected with COVID-19 at a training and research hospital between May 2020 and August 2020. Of the 53 women, 16 (30.2%) had leukopenia. The mean C-reactive protein level was 18.42 ± 59.33 mg/L. The mean procalcitonin level was 0.1 ± 0.21 µg/L. The liver function tests were within normal limits. The mean creatinine level was 0.58 ± 0.37 mg/dl. Elevated levels of α-fetoprotein (AFP) in 1 patient, elevated levels of carcinoembryonic antigen (CEA) in 2 patients, elevated levels of cancer antigen 125 (CA125) in 4 patients, elevated levels of CA19-9 in 2 patients, and elevated levels of CA15-3 in 2 patients were detected. One of 4 patients who were taken to the intensive care unit had elevated levels of AFP. In addition, 2 of 4 patients who were taken to the intensive care unit had elevated levels of CA125 and CA15-3. Except for AFP, levels of all tumor markers of the patient who died were high. We found that COVID-19 had no effect on tumor markers (CA125, CA19-9, CA15-3, AFP, and CEA).

Convalescent plasma, cytomegalovirus infection, and persistent leukopenia in COVID-19 recovery phase: What is the link?

Therapies used to tide over acute crisis of COVID-19 infection may lower the immunity, which can lead to secondary infection or a reactivation of latent infection. We report a 75-years-old male patient who had suffered from severe COVID-19 infection three weeks earlier and who had been treated with corticosteroids and convalescent plasma along with other supportive therapies. At time of discharge he had developed leukopenia which worsened at 1-week follow up visit. On 18th day post-discharge, he became very sick and was brought to our hospital with complaints of severe persistent dysphagia. During evaluation he was diagnosed to have an acute cytomegalovirus infection and severe oropharyngeal thrush. Both COVID-19 and cytomegalovirus are known to cause synergistic decrease in T cells and NK cells leading to immunosuppression. The patient made complete recovery with a course of intravenous ganciclovir and fluconazole. Persistent leukopenia in high risk and severely ill cases should give rise to a suspicion of COVID-19 and cytomegalovirus co-infection.

Magnitude and associated factors of peripheral cytopenia among HIV-infected children attending at University of Gondar Specialized Referral Hospital, Northwest Ethiopia.

BACKGROUND: Isolated or multi lineage cytopenia are the most common clinicopathological features and independently associated with increased risk of disease progression and death among human immunodeficiency virus infected children. In the study area, there is scarcity of data about the magnitude of various cytopenia. OBJECTIVES: Aimed to determine the magnitude and associated factors of peripheral cytopenia among HIV infected children at the University of Gondar Specialized Referral Hospital ART clinic, Northwest Ethiopia. METHODS: Institutional based cross-sectional study was conducted on 255 HIV infected children from January- April 2020. None probable convenient sampling technique was used to select the study participant. Socio demographic data were collected by pre tested structured questionnaire via face-to-face interview and their medical data were obtained from their follow-up medical records. Moreover, blood specimens were collected and examined for complete blood count, viral load and blood film, whereas stool specimens were collected and examined for intestinal parasites. Bi-variable and multi-variable logistic regression models were fitted to identify associated factors of cytopenia. P-Value <0.05 was considered as statistically significant. RESULT: The overall magnitude of peripheral cytopenia was 38.9%. Anemia, leukopenia, lymphopenia, thrombocytopenia and bi-cytopenia were 21.2%, 12.2%, 11%, 1.6% and 3.9% respectively. Being in the age group of 2-10 years (AOR = 5.38, 95%CI 2.33-12.46), AZT based regimen (AOR = 5.44, 95%CI: 2.24-13.21), no eating green vegetables (AOR = 2.49, 95% CI: 1.26-4.92) and having plasma viral load >1000 copies /ml (AOR = 5.38, 95%CI: 2.22-13.03) showed significant association with anemia. CONCLUSION: Anemia was the predominant peripheral cytopenia among HIV infected children in this study. It was strongly associated with AZT based drug type, age below 10 years and high viral load. Critical stress should be given for early investigation and management of cytopenia in addition to the use of alternative drug which leads to higher viral suppression and lower risk of toxicity issue.

Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity.

BACKGROUND: Exposure to viral or bacterial pathogens increases the number of neutrophils with a relative decrease in lymphocytes, leading to elevated neutrophil to lymphocyte ratio (NLR). This study aimed to investigate whether differences in NLR among real-time polymerase chain reaction (PCR)-positive and -negative patients presenting with a prediagnosis of COVID-19 pneumonia could be useful in the differential diagnosis. METHODS: The study included 174 patients admitted because of suspected COVID-19 infection between March and April 2020. Patients were divided into two groups: PCR-negative and PCR-positive. Hemogram, NLR, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, ferritin, D-dimer, C-reactive protein, procalcitonin, troponin, and coagulation parameters were analyzed. RESULTS: On comparison of laboratory parameters between both groups at presentation, PCR-positive patients were significantly more likely to have leukopenia (p < 0.001), thrombocytopenia (p = 0.006), neutropenia (p < 0.001), lymphopenia (p = 0.001), and increased NLR (p = 0.003). Furthermore, PCR-positive patients showed significant elevations of ferritin (p = 0.012) and procalcitonin (p = 0.038) and significant lower potassium levels (p = 0.05). CONCLUSION: COVID-19 pneumonia has become a major global health problem. Early diagnosis and treatment of these patients are crucial, as COVID-19 pneumonia shows a rapid progression in most cases. Thus, leukopenia, thrombocytopenia, elevated NLR, and elevated ferritin may be useful as supplementary diagnostic tests in these patients, which may allow early initiation of treatment and may contribute to preventing progression in patients with abnormal results.

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19.

Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

CT Manifestations and Clinical Characteristics of 1115 Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: We aimed to assess the prevalence of significant computed tomographic(CT) manifestations and describe some notable features based on chest CT images, as well as the main clinical features of patients with coronavirus disease 2019(COVID-19). MATERIALS AND METHODS: A systematic literature search of PubMed, EMBASE, the Cochrane Library, and Web of Science was performed to identify studies assessing CT features, clinical, and laboratory results of COVID-19 patients. A single-arm meta-analysis was conducted to obtain the pooled prevalence and 95% confidence interval (95% CI). RESULTS: A total of 14 articles (including 1115 patients) based on chest CT images were retrieved. In the lesion patterns on chest CTs, we found that pure ground-glass opacities (GGO) (69%, 95% CI 58-80%), consolidation (47%, 35-60%) and "air bronchogram sign" (46%, 25-66%) were more common than the atypical lesion of "crazy-paving pattern" (15%, 8-22%). With regard to disease extent and involvement, 70% (95% CI 46-95%) of cases showed a location preference for the right lower lobe, 65% (58-73%) of patients presented with ≥3 lobes involvement, and meanwhile, 42% (32-53%) of patients had involvement of all five lobes, while 67% (55-78%) of patients showed a predominant peripheral distribution. An understanding of some important CT features might be helpful for medical surveillance and management. In terms of clinical features, muscle soreness (21%, 95% CI 15-26%) and diarrhea (7%, 4-10%) were minor symptoms compared to fever (80%, 74-87%) and cough (53%, 33-72%). CONCLUSION: Chest CT manifestations in patients with COVID-19, as well as its main clinical characteristics, might be helpful in disease evolution and management.

Epidemiological and genetic investigation of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus.

BACKGROUND: To analyze and discuss the transmission route of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). METHOD: We performed an epidemiological investigation and a genetic analysis of patients with severe fever with thrombocytopenia syndrome (SFTS) caused by SFTSV, their close contacts and the surrounding population. RESULTS: We found that all patients had contact with the blood of the first patient. The comparison of gene sequences in the three isolated SFTSV strains showed that the strains were closely related. Six close contacts and nine individuals in the surrounding population were positive for SFTSV IgM antibody. CONCLUSION: We suspect that the cluster outbreak was transmitted via blood and that the natural reservoir host of SFTSV exists in the patients' environment.

Unusual case of severe fever with thrombocytopenia syndrome showing clinical manifestations in a companion dog.

Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging zoonotic virus in East Asia. However, SFTS virus (SFTSV) has not been reported to cause clinical infection in companion dogs to date. We report the case of a 4-year-old companion dog that presented with fever, vomiting, leukocytopenia and thrombocytopenia at a veterinary hospital in the Republic of Korea. It was diagnosed with SFTS, which was confirmed using real-time reverse transcription PCR, sequencing and an indirect immunofluorescence assay, and recovered after supportive care. Further studies are required to investigate SFTSV infection in companion animals, living in close contact with humans, as well as animal-to-human transmission.

The clinical profile, hematological parameters and liver transaminases of dengue NS1 Ag positive patients admitted to Jaffna Teaching Hospital, Sri Lanka.

OBJECTIVE: Objective of the study is to evaluate the on-admission day symptoms and signs, clinical, hematological parameters and liver transaminases of the dengue NS1 positive patients who got admitted on different clinical phases [Febrile phase (day 1-3) and Critical phase(day 4-5)] of dengue at medical wards of Jaffna Teaching Hospital. RESULTS: Blood samples were collected from 150 suspected dengue patients from day 1 to 5 of the illness. Seventy-eight patients were positive for dengue NS1, according to the WHO proposed dengue clinical phase framework 37 patients were from febrile phase and 41 patients from critical phase. Patients who admitted on critical phase framework suffered from leukopenia and thrombocytopenia. Nine patients had the evidence of leakage with fever and the leakers had significant rise in hemoglobin, hematocrit and liver transaminase levels which are considered as severe form of the disease.

Severe fever with thrombocytopenia syndrome: comparison with scrub typhus and clinical diagnostic prediction.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Asian 3 countries, China, Japan and Korea, which are scrub typhus endemic areas, and its incidence is increasing. As the two infections overlap epidemiologically and clinically and the accessibility or sensitivity of diagnostic tests is limited, early clinical prediction may be useful for diagnostic and therapeutic purposes. METHODS: Patients aged ≥16 years who were clinically suspected and laboratory-confirmed to be infected with Orientia tsutsugamushi or the SFTS virus in South Korea were enrolled. Clinical and laboratory parameters were compared. Scrub typhus was further subclassified according to the status of eschar and skin rash. An SFTS prediction scoring tool was generated based on a logistic regression analysis of SFTS compared with scrub typhus. RESULTS: The analysis was performed on 255 patients with scrub typhus and 107 patients with SFTS. At initial presentation, subjective symptoms except for gastrointestinal symptoms, were more prominent in scrub typhus patients. In addition to the characteristic eschar and skin rash, headache was significantly more prominent in scrub typhus, while laboratory abnormalities were more prominent in SFTS. Leukopenia (white blood cell count < 4000/mm3; odds ratio [OR] 30.13), thrombocytopenia (platelet count < 80,000 /mm3; OR 19.73) and low C-reactive protein (< 1 mg/dL; OR 67.46) were consistent risk factors for SFTS (all P < 0.001). A prediction score was generated using these 3 variables, and a score ≥ 2 had a sensitivity of 93.1% (95% confidence interval [CI], 87.9-96.4%) and a specificity of 96.1% (95% CI, 93.8-97.6%) for SFTS. CONCLUSION: This prediction scoring tool may be useful for differentiating SFTS from eschar- or skin rash-negative scrub typhus. It is a simple and readily applicable tool with potential for use in primary care settings.

Clinical and Laboratory Characteristics of an Acute Chikungunya Outbreak in Bangladesh in 2017.

From April to September 2017, Bangladesh experienced a huge outbreak of acute Chikungunya virus infection in Dhaka. This series describes the clinical and laboratory features of a large number of cases (690; 399 confirmed and 291 probable) suffered during that period. This observational study was carried out at Dhaka Medical College Hospital, Bangladesh. The median age of the patients at presentation was 38 years (IQR 30-50) with a male (57.3%) predominance. Hypertension and diabetes were the most common comorbidities. The mean (±SD) duration of fever was 3.7 (±1.4) days. Other common manifestations were arthralgia (99.2%), maculopapular rash (50.2%), morning stiffness (49.7%), joint swelling (48.5%), and headache (37.6%). Cases were confirmed by anti-chikungunya IgG (173; 43.3%), IgM (165; 42.3%), and reverse transcription polymerase chain reaction (44; 11.0%). Important laboratory findings include high erythrocyte sedimentation rate (156; 22.6%), raised serum glutamic pyruvic transaminase (73; 10.5%), random blood sugar (54; 7.8%), leukopenia (72; 10.4%), thrombocytopenia (41; 5.9%), and others. The oligo-articular (453; 66.1%) variety of joint involvement was significantly more common compared with the poly-articular (237; 34.5%) variety. Commonly involved joints were the wrist (371; 54.1%), small joints of the hand (321; 46.8%), ankle (251; 36.6%), knee (240; 35.0%), and elbow (228; 33.2%). Eleven cases were found to be complicated with neurological involvement and two of them died. Another patient died due to myocarditis. Public health experts, clinicians, and policymakers could use the results of this study to construct the future strategy tackling chikungunya in Bangladesh and other epidemic countries.

[Severe fever with thrombocytopenia syndrome: epidemiology, pathophysiology, and development of specific treatment and prevention measures].

Severe fever with thrombocytopenia syndrome (SFTS) was first reported in 2011 as an emerging virus infection caused by a novel Phlebovirus in the Bunyaviridae family [SFTS virus (SFTSV)]. In addition, it was reported to be endemic to Hubei, Henan, Shandong, and Heilongjiang provinces in China. The primary symptoms of SFTS are gastrointestinal symptoms such as fever, general fatigue, nausea, vomiting, and diarrhea. The total blood cell counts in patients with SFTS reveal thrombocytopenia and leukopenia. A woman in her 50s died due to multiorgan failure, intestinal hemorrhage, and hemophagocytosis in the autumn of 2012. She was retrospectively diagnosed with SFTS, suggesting that SFTS was endemic not only to China but also to Japan. Subsequently, SFTS was reported to be endemic to South Korea as well. Approximately 5 years have passed since the discovery of SFTS endemicity in Japan. To date, 40-100 patients with SFTS from the western part of Japan have been reported annually to the National Institute of Infectious Diseases. The case-fatality rate of SFTS is approximately 20%. This high case-fatality rate could be attributed to multiorgan failure, coagulopathy, and hemophagocytosis, which are induced in most patients with SFTS. Reportedly, an antiviral drug, favipiravir, was effective in treating SFTSV infection in an animal infection model. SFTSV has been found to circulate between wild animals and several species of ticks in nature, suggesting that we cannot escape the risk of infection with SFTSV and that SFTS will continue to occur in endemic areas. Hence, the development of specific treatment and preventive measures with SFTS vaccines is imperative.

Leukopenia and lack of ribavirin predict poor outcomes in patients with haematological malignancies and respiratory syncytial virus infection.

Objectives: Respiratory syncytial virus (RSV) infection causes morbidity and mortality in cancer patients. However, studies describing this infection in patients with haematological malignancies are scarce. We sought to evaluate the clinical impact of RSV infection on this patient population. Methods: We reviewed the records of patients with haematological malignancies and RSV infections cared for at our institution between January 2000 and March 2013. Results: Of the 181 patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%) had multiple myeloma. Most patients [117 (65%)] presented with an upper respiratory tract infection (URTI) and 15 (13%) had a subsequent lower respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day mortality rate was 15%. Multivariable regression analysis showed that having both neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P < 0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR = 0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI. Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI = 1.24-15.0, P = 0.021). Conclusions: Patients with haematological malignancies and RSV infections, especially those with immunodeficiency, may be at risk of LRTI and death; treatment with ribavirin during RSV URTI may prevent these outcomes.

Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs.

Classical swine fever virus (CSFV) causes a highly lethal disease in pigs, which is characterized by immunosuppression. Leukopenia is known to be a possible mechanism of immunosuppression during CSFV infection. As a new and specialized form of cell death, pyroptosis is the key response of the innate immune system to pathogens, and is widely involved in the occurrence and development of infectious diseases. However, the relationship between CSFV and pyroptosis has not been explored. In this study, we investigated the occurrence of pyroptosis in pigs following CSFV infection. According to qRT-PCR assay results, the prevalence of this virus in peripheral lymphoid organs (tonsils, lymph nodes, and spleen) was much higher than that in other organs. Severe bleeding, necrosis, and a significant reduction in lymphocytes were found in the peripheral lymphoid organs of CSFV-infected pigs based on histological examination. In-depth studies showed that an increased ratio of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were present in the peripheral lymphoid organs of the CSFV-infected group according to immunohistochemistry. Meanwhile, the p10 subunit and activity of caspase-1, which is a regulator of pyroptosis, the N-terminal domain of gasdermin D, which is an executor of pyroptosis, and the cleavage and secretion of IL-1b, which is a product of pyroptosis were increased in the peripheral lymphoid organs of the CSFV-infected group. Together, these results demonstrated that pyroptosis is involved in CSFV-induced cell death in vivo, which provides a new understanding of the mechanism associated with lymphocyte depletion and immunosuppression in pigs infected with this virus.

Factors associated with Severe Fever with Thrombocytopenia Syndrome infection and fatal outcome.

Severe fever with thrombocytopenia syndrome (SFTS) is emerging in China and the incidence increased year by year. In this study, we conducted case control study to explore factors associated with SFTS virus (SFTSV) infection and fatal outcome. In the study of factors associated with SFTSV infection, a total of 216 individuals participated the study, including 72 cases and 144 matched controls. There were significant differences in proportion of history of tick bite and breeding domestic animals between cases and controls. Of note, individuals who were unclear whether they had been bitten by ticks had the highest risk of SFTSV infection and odds ratio (OR) was 10.222. In the study of factors associated with SFTS fatal outcome, a total of 129 cases participated the study including 16 deaths and 113 survivors. Significant differences were observed in body mass index (BMI), intervals from illness onset to confirmation, and proportion of gingival hemorrhage between deaths and survivors, whose ORs of these factors were 3.903, 1.996, and 3.826, respectively. Our results suggest that all patients with fever, thrombocytopenia and leukocytopenia in SFTS endemic areas should be suspected of SFTS, even they don't have history of tick bite, and more intense treatment should be administered to patients with abnormal BMI before laboratory parameters are detected.

Bone marrow findings in severe fever with thrombocytopenia syndrome: prominent haemophagocytosis and its implication in haemophagocytic lymphohistiocytosis.

AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus; primary manifestations are fever, thrombocytopenia, leukopenia and gastrointestinal symptoms. Before an aetiological diagnosis is made, SFTS patients can undergo bone marrow examination due to cytopenias. Although several studies have reported on bone marrow examination in SFTS patients, most do not provide adequate details. Bone marrow findings in SFTS patients were investigated in this study. METHODS: An observational study was conducted in SFTS patients who were hospitalised between 2013 and 2014 in two university hospitals in South Korea. Patients were included in the study if SFTS was confirmed by real-time PCR for the SFTS virus and a bone marrow examination was conducted. The morphologic findings of the bone marrow samples were reviewed. RESULTS: Three cases met the study inclusion criteria. One patient died of multiple organ failure. Haemophagocytosis was evident in the bone marrow samples of all three patients. Histiocytic hyperplasia and haemophagocytosis were more pronounced in the fatal case. One patient was diagnosed as having haemophagocytic lymphohistiocytosis. CONCLUSIONS: Haemophagocytosis in the bone marrow of SFTS patients may be common. In SFTS endemic areas, SFTS should be one of the differential diagnoses of fever of unknown origin with haemophagocytosis in the bone marrow.

The evolutionary history and spatiotemporal dynamics of the fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV) in China.

BACKGROUND: In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces. Human-to-human transmission has been documented, indicating that FTLSV should be considered a potential public health threat. Determining the historical spread of FTLSV could help curtail its spread and prevent future movement of this virus. METHOD/PRINCIPAL FINDINGS: To examine the pattern of FTLSV evolution and the origin of outbreak strains, as well to examine the rate of evolution, the genome of 12 FTLSV strains were sequenced and a phylogenetic and Bayesian phylogeographic analysis of all available FTLSV sequences in China were performed. Analysis based on the FTLSV L segment suggests that the virus likely originated somewhere in Huaiyangshan circa 1790 (95% highest probability density interval: 1756-1817) and began spreading around 1806 (95% highest probability density interval: 1773-1834). Analysis also indicates that when FTLSV arrived in Jiangsu province from Huaiyangshan, Jiangsu Province became another source for the spread of the disease. Bayesian factor test analysis identified three major transmission routes: Huaiyangshan to Jiangsu, Jiangsu to Liaoning, and Jiangsu to Shandong. The speed of FTLSV movement has increased in recent decades, likely facilitated by modern human activity and ecosystem changes. In addition, evidence of RNA segment reassortment was found in FTLSV; purifying selection appears to have been the dominant force in the evolution of this virus. CONCLUSION: Results presented in the manuscript suggest that the Huaiyangshan area is likely be the origin of FTLSV in China and identified probable viral migration routes. These results provide new insights into the origin and spread of FTLSV in China, and provide a foundation for future virological surveillance and control.

Severe fever with thrombocytopenia syndrome, Shandong Province, China, 2011.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China. The incidence and clinical and laboratory characteristics of SFTS are not clearly defined. During May 22-October 2, 2011, a total of 24 patients with fever, thrombocytopenia, and leukopenia were clinically diagnosed as having SFTS in Yiyuan County, Shandong Province, China. We conducted laboratory tests for these SFTS patients. SFTS virus (SFTSV) infection was confirmed in 22 patients by using reverse transcription PCR and ELISA by acute-phase and convalescent-phase serum samples. Clinical and laboratory manifestations included fever (100%), gastrointestinal symptoms (91%), myalgia (55%), chills (41%), thrombocytopenia (100%), and leukopenia (95%).