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Dengue disease is a major problem worldwide, impacting millions of people annually with no specific approved treatments. The pathogenesis of dengue is a complex interplay of viral and host factors, driven in particular by an excessive inflammatory response triggered by the infection. While it has been observed that various viruses can modulate the PI3K/Akt signaling pathway to aid replication and theunderlying mechanisms remainunclear. The study aims to explore the impact of PI3Kγ inhibition during Dengue virus (DENV) infection in vivo. Experiments were performed using both wild-type (WT) and PI3Kγ knockout mice inoculated with DENV. Parameters, including survival rates, hematologic, virologic, histopathologic, and inflammatory analyzes, were evaluated. Additionally, the therapeutic potential of a selective PI3Kγ inhibitor (AS605240) was investigated in DENV-infected A129 mice. PI3Kγ deficiency resulted in lower lethality and provided protection against DENV-induced thrombocytopenia, decreased hemoconcentration, vascular permeability, and liver damage compared to DENV-infected WT littermates. In addition, PI3Kγ deficiency correlated with reduced viral replication in the blood, spleen and liver alongside decreased production of inflammatory mediators in plasma and spleen. Pharmacologic inhibition of PI3Kγ not only ameliorated DENV-induced thrombocytopenia and liver injury, but also reduced DENV replication in target organs. Treatment with AS605240 reduced the concentration of IL-6 in the spleen and plasma.This study sheds light on the significant pro-viral effects of the PI3Kγ signaling pathway during DENV infection and its central role in pathogenesis by curbing excessive DENV-induced inflammation. Inhibition of PI3Kγ shows promising host-directed target for developing novel Dengue disease therapies, offering substantial benefits to hosts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Souza DG reports financial support was provided by Minas Gerais State Foundation of Support to the Research. Teixeira MM reports financial support was provided by National Council for Scientific and Technological Development. Teixeira MM reports financial support was provided by Minas Gerais State Foundation of Support to the Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever ( p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day ( p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Melissa E. Day et al.)

Dengue infection is caused by the dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries, with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease, which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormalities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research.

Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cabrera, Tietäväinen, Jokiranta, Mäkelä, Vaheri, Mustonen, Vapalahti, Kanerva and Strandin.)

We aimed to describe the landscape, including molecular, epidemiological, and clinical aspects of CHIKV infections in the Ribeirao Preto region, an area endemic to dengue. We randomly screened 3744 plasma samples that had undergone DENV diagnosis to evaluate CHIKV-RNA using an in-house RT-PCR assay. Positive samples were followed clinically, and RNA samples were submitted to whole genome sequencing. Seventeen cases (0.5 %) were positive for CHIKV-RNA despite being negative for DENV-RNA. Notably, half of the patients experienced prolonged arthralgia lasting more than 90 days. Compared with the healthy control group, leukopenia and thrombocytopenia were observed in all CHIKV-positive individuals with statistically significant P values (P < 0.0001 and P = 0.0003, respectively). The genomic analysis revealed that the CHIKV strains being studied are classified within the East-Central-South-African (ECSA) genotype. This analysis identified new mutations, E1: K211E and E2: V264A, while the previously known mutation E1: A226V was not detected among these strains. This study highlights the need for epidemiological surveillance and preparedness for potential CHIKV epidemics in Brazil, particularly where other arboviruses co-circulate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A 76-year-old woman infected with Yezo virus (YEZV) developed liver dysfunction and thrombocytopenia following a tick bite. Despite the severity of her elevated liver enzymes and reduced platelet counts, the patient's condition improved spontaneously without any specific treatment. To our knowledge, this represents the first documented case where the YEZV genome was detected simultaneously in a patient's serum and the tick (Ixodes persulcatus) that bit the patient. This dual detection not only supports the hypothesis that YEZV is a tick-borne pathogen but also underscores the importance of awareness and diagnostic readiness for emerging tick-borne diseases, particularly in regions where these ticks are prevalent., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications., Methods: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018., Results: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6., Conclusion: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To examine D-dimer, coagulation profile, and platelet count among patients hospitalized with coronavirus disease-19 (COVID-19) and compare them to findings from non-COVID-19 subjects., Methods: The participants in this retrospective hospital-based observational study design included 112 confirmed diagnosed with COVID-19 who were admitted to King Khaled Hospital, Najran, Saudi Arabia, and another 112 non-COVID-19 subjects as a comparative group. Laboratory investigations, demographic and clinical records were obtained from participants' electronic indexed medical records. Coronavirus disease-19 diagnosis was confirmed according to positive real time polymerase chain reaction assay carried out at the hospital's central laboratory, where samples were extracted from a nasopharyngeal swab. Pneumonia related to COVID-19 is classified as critical, severe, moderate, mild, and asymptomatic whereas thrombocytopenia was marked when the platelet count was <150.00×10 9 /L. Suitable statistical analysis was applied to determine possible differences between the findings from the 2 groups., Results: The D-dimer and activated partial thromboplastin clotting time mean values were significantly elevated ( p <0.001). The international normalized ratio and platelet count mean values confirmed a significant decrease ( p <0.001). Thrombocytopenia was found 9 times in COVID-19 higher than in the non-COVID-19. D-dimer and prothrombin time mean values increased significantly among the COVID-19 patients with all patterns of symptoms on admission ( p <0.001)., Conclusion: D-dimer mean values increased significantly in deceased COVID-19 and in hospitalized intensive care unit (ICU) wards patients ( p <0.001), indicating a potential predictive and prognostic severity marker, particularly among COVID-19 patients in the ICU., (Copyright: © Saudi Medical Journal.)

Dengue is one of the most important vector-borne viral illnesses found in tropical and subtropical regions. Colombia has one of the highest rates of dengue cases in the Americas. Severe dengue virus (DENV) infection presents with capillary leakage, hemorrhage, and organ compromise, eventually leading to death. Over the years, there have been many efforts to develop a vaccine that guarantees protective immunity, but they have been partially successful, as such immunity would need to guarantee protection against four distinct viral serotypes. Absolute platelet count is a laboratory parameter used to monitor the clinical progression of DENV, as infection is often accompanied by thrombocytopenia. Although this finding is well described with respect to the natural history of the disease, there are various hypotheses as to the cause of this rapid decrease, and several in vivo and ex vivo models have been used to explain the effect of DENV infection on platelets and their precursors. DENV infects and activates platelets, facilitating their elimination through recognition by phagocytic cells and peripheral margination. However, infection also affects the precursors in the bone marrow by modulating megakaryopoiesis. The objective of this article is to explore various proposed mechanisms of DENV-induced thrombocytopenia to better understand the pathophysiology and clinical presentations of this highly relevant viral infection.

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., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Ahmed M. E. Elkhalifa et al.)

Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses.

Thrombocytopenia is noted in corona virus disease-2019 (COVID-19) with a prevalence of 5% to 41%, and has been observed to be associated with inferior outcomes. The pathogenesis of thrombocytopenia in COVID-19 is unique and differs from other viral syndromes in terms of clinical presentation and causative mechanisms. Platelets act as both targets and the initial defense against severe acute respiratory syndrome-coronavirus 2 and work in concert with the underlying thrombophilic mechanisms to modulate the final disease phenotype. Understanding these mechanisms may possibly allow targeting of a key component of COVID-19 pathogenesis. We provide a focused review of the current mechanisms implicated in development of thrombocytopenia in COVID-19 and therapeutic implications of the same., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The literature regarding coronavirus disease of 2019 (COVID-19) infection in pediatrics indicates that children have less severe clinical presentations and lower mortality rates. There remains limited data regarding hematologic sequelae in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Romiplostim has shown a platelet response in pediatric patients with chronic immune thrombocytopenic purpura, and eltrombopag is proven to increase platelet counts in patients with inherited thrombocytopenia. We review SARS-CoV-2-associated thrombocytopenia and present a pediatric patient with acute on chronic thrombocytopenia in the setting of COVID-19 with subsequent platelet recovery using romiplostim., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The immune and inflammatory responses of platelets to human immunodeficiency virus 1 (HIV-1) and its envelope proteins are of great significance to both the treatment of the infection, and to the comorbidities related to systemic inflammation. Platelets can interact with the HIV-1 virus itself, or with viral membrane proteins, or with dysregulated inflammatory molecules in circulation, ensuing from HIV-1 infection. Platelets can facilitate the inhibition of HIV-1 infection via endogenously-produced inhibitors of HIV-1 replication, or the virus can temporarily hide from the immune system inside platelets, whereby platelets act as HIV-1 reservoirs. Platelets are therefore both guardians of the host defence system, and transient reservoirs of the virus. Such reservoirs may be of particular significance during combination antiretroviral therapy (cART) interruption, as it may drive viral persistence, and result in significant implications for treatment. Both HIV-1 envelope proteins and circulating inflammatory molecules can also initiate platelet complex formation with immune cells and erythrocytes. Complex formation cause platelet hypercoagulation and may lead to an increased thrombotic risk. Ultimately, HIV-1 infection can initiate platelet depletion and thrombocytopenia. Because of their relatively short lifespan, platelets are important signalling entities, and could be targeted more directly during HIV-1 infection and cART., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pretorius.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The novel coronavirus SARS-CoV-2, responsible for the 2019-2020 global (COVID-19) pandemic, is a respiratory virus associated with the development of thromboembolic complications and respiratory failure in severe cases. Increased risk of pulmonary embolism and thrombosis has been identified in COVID-19 patients, alongside accompanying elevations in potential prognostic biomarkers, including D-dimer, IL-6 and cardiac specific troponins. Our aim was to provide a scoping review of the available literature regarding thrombosis risk, other cardiovascular implications, and their biomarkers in COVID-19 to highlight potential disease mechanisms., Methods: Authors conducted a literature search in PubMed using MeSH headings "disseminated intravascular coagulation", "pulmonary embolism", "thromb*", "stroke", "myocardial infarction" and "acute lung injury", as well as terms "COVID-19", "SARS-CoV-2", "2019 novel coronavirus" and "2019-nCoV"., Results and Conclusions: COVID-19 disease is characterised by the interactions between hyperactive coagulation and complement systems - induced by hyper-inflammatory conditions, resulting in a pro-thrombotic state and diffuse tissue injury. There are several promising prognostic markers of disease severity, with D-dimer the most significant. The presence of thrombocytopenia appears to be a key indicator of patient deterioration. Further research is required to understand the underlying pathophysiology in COVID-19 and its implications in disease progression and patient management. Randomised trials are urgently needed to determine the safety of proposed therapeutic anticoagulation with heparin and the role for anti-platelet agents, such as Ticagrelor, in patient management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Thrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID-19) in patients with immune thrombocytopenia (ITP), a retrospective single-centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS-CoV-2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID-19 could explain this paradoxical effect, although further studies are needed., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Viral nephropathy is a term defines glomerular, tubular and/or vascular injury in kidney caused by viruses itself or virus-induced immune mechanisms. It is difficult to prove causality between the renal disease and the viral infection, however, renal biopsy findings can help in this regard. Several viruses such as hepatitis B and C, Human immun deficiciency virus (HIV), Hantavirus, Cytomegalovirus (CMV), an recently Coronavirus are shown to affect the kidney. Treatment of viral nephropathies are unique regarding the diagnosis which can be made only with renal biopsy in most of the situations. We present two patients presented with acute kidney injury and thrombocytopenia caused by different viruses (Hantavirus and HIV) that affect multiple areas in kidney that revealed with kidney biopsy. Supportive treatment in the patient with Hantavirus nephropathy and HIV treatment along with eculizumab and supportive treatment in the patient with HIVAN were successfully implemented.

The current pandemic due to coronavirus disease 2019 (COVID-19) has posed an unprecedented challenge for the medical communities, various countries worldwide, and their citizens. Severe acute respiratory syndrome coronavirus 2 has been studied for its various pathophysiological pathways and mechanisms through which it causes COVID-19. In this study, we discussed the immunological impact of COVID-19 on the hematological system, platelets, and red blood cells., (© 2020 Wiley Periodicals LLC.)

Coronavirus disease 2019 (COVID-19) is affecting millions of patients worldwide. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the family Coronaviridae, with 80% genomic similarities to SARS-CoV. Lymphopenia was commonly seen in infected patients and has a correlation to disease severity. Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors. This pandemic has caused disruption in communities and hospital services, as well as straining blood product supply, affecting chemotherapy treatment and haematopoietic stem cell transplantation schedule. In this article, we review the haematological manifestations of the disease and its implication on the management of patients with haematological disorders., (© 2020 S. Karger AG, Basel.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing spread. Currently SFTS transmission has expanded beyond Asian countries, however, with definitive global extents and risk patterns remained obscure. Here we established an exhaustive database that included globally reported locations of human SFTS cases and the competent vector, Haemaphysalis longicornis ( H. longicornis ), as well as the explanatory environmental variables, based on which, the potential geographic range of H. longicornis and risk areas for SFTS were mapped by applying two machine learning methods. Ten predictors were identified contributing to global distribution for H. longicornis with relative contribution ≥1%. Outside contemporary known distribution, we predict high receptivity to H. longicornis across two continents, including northeastern USA, New Zealand, parts of Australia, and several Pacific islands. Eight key drivers of SFTS cases occurrence were identified, including elevation, predicted probability of  H. longicornis presence, two temperature-related factors, two precipitation-related factors, the richness of mammals and percentage coverage of water bodies. The globally model-predicted risk map of human SFTS occurrence was created and validated effective for discriminating the actual affected and unaffected areas (median predictive probability 0.74 vs. 0.04, P  < 0.001) in three countries with reported cases outside China. The high-risk areas (probability ≥50%) were predicted mainly in east-central China, most parts of the Korean peninsula and southern Japan, and northern New Zealand. Our findings highlight areas where an intensive vigilance for potential SFTS spread or invasion events should be advocated, owing to their high receptibility to H. longicornis distribution.

The emergence of the Coronavirus Disease -19 (COVID-19) pandemic, has had a tremendous global impact, resulting in substantial morbidity and mortality worldwide and especially in the United States, where nearly one third of the cases are located. Although involvement of the lower respiratory track accounts for most of the morbidity and mortality seen, the virus involves several organ systems and the syndrome exhibits clinical diversity with a wide range of symptoms and manifestations. The involvement of elements of the hematopoietic system is prominent in severe cases and associated with poor outcomes and mortality. Lymphopenia, leukopenia, thrombocytopenia, disseminated intravascular coagulation, and a prothrombotic state are common manifestations of COVID-19 and have important treatment and prognostic implications. Better understanding of the mechanisms of the pathophysiology of COVID-19-induced hematological abnormalities may ultimately result in better ways to treat them and decrease the associated morbidity and mortality.

Background: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection., Objectives: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias., Methods: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs., Results: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children., Conclusions: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). Although SFTS originated in China, it is an emerging infectious disease with prevalence confirmed in Japan, Korea, and Vietnam. The full-length genomes of 51 Korean SFTSV isolates from 2013 to 2016 were sequenced, and the sequences were deposited into a public database (GenBank) and analyzed to elucidate the phylogeny and evolution of the virus. Although most of the Korean SFTSV isolates were closely related to previously reported Japanese isolates, some were closely related to previously reported Chinese isolates. We identified one Korean strain that appears to have resulted from multiple inter-lineage reassortments. Several nucleotide and amino acid variations specific to the Korean isolates were identified. Future studies should focus on how these variations affect virus pathogenicity and evolution.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS., Competing Interests: The authors have declared that no competing interests exist.

Background: Thrombocytopenia was common in the coronavirus disease (Covid-19) patients during the infection, especially in severe COVID-19 patients, but was less in the non-severe Covid-19 patients. However, the platelet count would be restored after antivirus treatment. In this paper, we report continuous thrombocytopenia in a non-severe Covid-19 case after a negative nucleic acid test for Covid-19., Case Presentation: A non-severe COVID-19 patient had the platelet continuous decrease for several months after the SARS-CoV-2 nucleic acid turning negative, and without well response to the glucocorticoid. The dynamic change of platelet count followed that of the lymphocyte count. After excluding the medicines possibility, immune system disorders, other specific virus infection and specific antibody of platelet, the thrombocytopenia continuously lasted for several months. The upward trend did not begin until June 2020 and she took the tapering dose of prednisone under the instruction of the hematologist., Conclusion: Excluding other potentialities inducing thrombocytopenia, we highly hypothesized the SARS-CoV-2 may cause thrombocytopenia by disturbing the immune system to induce the thrombocytopenia in our report,, which needs longer time to restore the immune system and platelet count via the glucocorticoid. We firstly reported this case in order to contribute the clinician to better deal with the patients like this.

Background: HIV infection exacerbates the prognosis of HCV infection, with a faster progression of hepatitis. Hepatic fibrosis is the major disruption of the hepatic tissue architecture characterized by anarchic deposition and excess of the extracellular matrix. The objective of this study was to evaluate hepatic fibrosis in HIV/HCV co-infected individuals as compared to HCV mono-infected., Methods: A total of 97 participants (mean age 60.2 ± 14.3 years and 0.76 male/female sex ratio) was enrolled in a study conducted in Yaoundé, Cameroon from November 2018 to January 2019. Liver fibrosis was assessed by the APRI score (Aspartate Aminotransferase or AST/Platelet Ratio Index) which identifies the stage of fibrosis as classified by the Metavir system (F0 to F4). CD4 counts and plasmatic HIV viral load of HIV/HCV co-infected individuals were determined and the correlation between hepatic fibrosis and immuno-virological status established. Statistical analysis was done using Microsoft Excel 2016 and EpiInfo7 software., Results: A high proportion (63.6%) of HIV/HCV co-infected participants had an abnormal AST level: 73.6 ± 45.8 IU/L as compared to 58.5 ± 39.3 IU/L (59.3%) among HCV mono-infected participants. The frequency of thrombocytopenia was 63.6% with a mean platelet count of 137 ± 50 ×  10 3 IU/L in HIV/HCV co-infected participants as compared to 176 ± 67 × 10 3 IU/L in HCV mono-infected participants (38.4%). The progression of hepatic fibrosis in participants with clinically significant fibrosis: F2, F3 and F4 was higher among HIV/HCV co-infected and the mean APRI score was 1.7 ± 1.4 versus 1 ± 0.8 among HCV mono-infected (26.7%). All participants (100%) with detectable HIV viral load had clinically significant fibrosis compared to 33.4% in those with undetectable HIV viral load (p = 0.55). Only 42.9% participants with CD4 >  500 cells/μL had clinically significant fibrosis (p = 0.72) while 100% participants with CD4 <  200 cells/μL had clinically significant fibrosis (p = 0.58)., Conclusions: A high level of AST combined with thrombocytopenia (APRI score > 1.5) is an indicator of hepatic fibrosis in HIV/HCV co-infected individuals. Because of its non-invasive and less costly nature, the APRI score can be a suitable biomarker to monitor hepatic fibrosis in HIV/HCV co-infected individuals in resource constrained settings.

COVID-19 patients (n = 34) suffering from ARDS were treated with tocilizumab (TCZ). Outcome was classified in two groups: "Death" and "Recovery". Predictive factors of mortality were studied. Mean age was 75.3, mean oxygen (O 2 ) requirements 10.4 l/min. At baseline, all patients had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer and liver enzymes). 24 patients (70.5%) recovered after TCZ therapy and 10 died (29.5%). Deceased subjects differed from patients in whom treatment was effective with regard to more pronounced lymphopenia (0.6 vs 1.0 G/l; p = 0.037), lower platelet number (156 vs 314 G/l; p = 0.0001), lower fibrinogen serum level (0.6 vs 1.0 G/l; p = 0.03), higher aspartate-amino-transferase (108 vs 57 UI/l; p = 0.05) and greater O 2 requirements (11 vs 8 l/min; p = 0.003)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict interests., (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The SARS-CoV-2 infection has caused a pandemic with a case rate of over 290 000 lab-confirmed cases and over 40 000 deaths in the UK. There is little evidence to inform the optimal management of a patient presenting with new or relapsed acute idiopathic thrombocytopaenic purpura with concurrent SARS-CoV-2 infection. We present a case of severe thrombocytopaenia complicated by subdural haematoma and rectal bleed associated with COVID-19. A 67-year-old man, admitted with a non-productive cough and confusion, was found to be positive for COVID-19. Ten days after admission, his platelets decreased from 146×109/L to 2×109/L. His platelets did not increase despite receiving frequent platelet transfusions. He was non-responsive to corticosteroids and intravenous immunoglobulins. Romiplostim and eltrombopag were given and after 9 weeks of treatment, his platelet count normalised. He was deemed medically fit with outpatient follow-up in a haematology clinic., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Corona Virus Disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. Emerging genetic and clinical evidence suggests similarities between COVID-19 patients and those with severe acute respiratory syndrome and Middle East respiratory syndrome. Hematological changes such as lymphopenia and thrombocytopenia are not rare in COVID-19 patients, and a smaller population of these patients had leukopenia. Thrombocytopenia was detected in 5-41.7% of the patients with COVID-19. Analyzing the dynamic decrease in platelet counts may be useful in the prognosis of patients with COVID-19. However, the mechanisms underlying the development of thrombocytopenia remain to be elucidated. This review summarizes the hematological changes in patients infected with SARS-CoV-2 and possible underlying mechanisms of thrombocytopenia development., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with the high case-fatality rate, and lack of vaccines. We aimed to systematically analysed the epidemiological characteristics, clinical signs, routine laboratory diagnosis, risk factors, and outcomes., Methods: Documents on SFTS were collected by searching the Chinese National Knowledge Infrastructure, Wan Fang Data, PubMed, Embase, and Web of Science databases from 2011 to 2018. Meta-analysis was performed by using Review Manager and Stata software., Results: Twenty-five articles involving 4143 cases were included. Diarrhea (odds ratio (OR) =1.60, 95% confidence interval (CI): 1.06 to 2.42, P = 0.02), and vomiting (OR = 1.56, 95% CI: 1.01 to 2.39, P = 0.04) on admission were associated with the fatal outcomes of SFTS. Compared to patients with mild symptoms, patients with severe symptoms had significantly elevated levels of lactic acid dehydrogenase (standard mean difference (SMD) =1.27, 95% CI: 0.59 to 1.94), alanine aminotransferase (SMD = 0.55, 95% CI: 0.24 to 0.85), aspirate aminotransferase (SMD = 1.01, 95% CI: 0.69 to 1.32), and creatine kinase (SMD = 1.04, 95% CI: 0.74 to 1.33) but had reduced platelet counts (SMD = -0.87, 95% CI: - 1.16 to - 0.58) and albumin levels (SMD = -1.00, 95% CI: - 1.32 to - 0.68). The risk factors for poor prognosis included age (mean difference (MD) =6.88, 95% CI: 5.41 to 8.35) and farming (OR = 2.01, 95% CI: 1.06 to 3.80). For the risk factors of contracting SFTS, the incidence of SFTS related to tick bites was 24% [95% CI: 0.18 to 0.31]. The pooled case-fatality rate of SFTS patients was 18% [95% CI: 0.16 to 0.21]., Conclusions: China is the country with the highest incidence of SFTS. May to July was the peak of the epidemic, and farmers were a high-risk group. The risk factor for SFTS included age (poor prognosis) and tick bites (contracting SFTS). Patients with severe diarrhea and vomiting symptoms on admission should be noted. Clinicians could use routine laboratory parameters and clinical symptoms as references for clinically suspected cases, classification of SFTS, and timely treatment, especially in basic hospitals.

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., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications., (© 2020 by The American Society of Hematology.)

Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption.

Coronavirus disease 2019 (COVID-19) can affect the haematopoietic system. Thrombocytopenia at admission was prevalent, while late-phase or delayed-phase thrombocytopenia (occurred 14 days after symptom onset) is rare. This retrospective, single-centre study screened 450 COVID-19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25 to March 9, 2020. COVID-19-associated delayed-phase thrombocytopenia occurred in 11·8% of enrolling patients. The delayed-phase thrombocytopenia in COVID-19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed-phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed-phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also provided and described bone marrow aspiration pathology of three patients with delayed-phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune-mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients. In addition, clinicians need to pay attention to the delayed-phase thrombocytopenia especially at 3-4 weeks after symptom onset., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: Thrombocytopenia is associated with many viral infections suggesting virions interact with and affect platelets. Consistently, viral particles are seen inside platelets, and platelet activation markers are detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, and are activated by a model virion. Approach and Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy, and transgenic mouse models, we probed the interactions between platelets and virions. Mouse platelets used known endocytic machinery, that is, dynamin, VAMP (vesicle-associated membrane protein)-3, and Arf6 (ADP-ribosylation factor 6), to take up and traffic HIV-1 pseudovirions. Endocytosed HIV-1 pseudovirions trafficked through early (Rab4 + ) and late endosomes (Rab7 + ), and then to an LC3 + (microtubule-associated protein 1A/1B-light chain 3) compartment. Incubation with virions induced IRAK4 (interleukin 1 receptor-associated kinase 4), Akt (protein kinase B), and IKK (IκB kinase) activation, granule secretion, and platelet-leukocyte aggregate formation. This activation required TLRs (Toll-like receptors) and MyD88 (myeloid differentiation primary response protein 88) but was less extensive and slower than activation with thrombin. In vivo, HIV-1 pseudovirions injection led to virion uptake and platelet activation, as measured by IKK activation, platelet-leukocyte aggregate formation, and mild thrombocytopenia. All were decreased in VAMP-3 -/- and, megakaryocyte/platelet-specific, Arf6 -/- mice. Similar platelet activation profiles (increased platelet-leukocyte aggregates, plasma platelet factor 4, and phospho-IκBα) were detected in newly diagnosed and antiretroviral therapy-controlled HIV-1 + patients., Conclusions: Collectively, our data provide mechanistic insights into the cell biology of how platelets endocytose and process virions. We propose a mechanism by which platelets sample the circulation and respond to potential pathogens that they take up.