Coinfection with Parvovirus B19 and Epstein Barr Virus in An Adolescent with Sickle Cell Disease Manifesting As Septic Shock

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4854-4854
Author(s):  
Jyoti Panicker ◽  
Robyn Gartrell Harris ◽  
Stephen Dale Smith

Abstract Abstract 4854 Patients with Sickle Cell Disease (SCD) are at an increased risk of serious and life-threatening infections. Epstein Barr Virus (EBV) and Human Parvovirus B19 (HPV-B19) are common viral infections that are usually asymptomatic or self-limiting in healthy children. However, SCD patients can have significant morbidity and mortality caused by these infections. In patients with SCD, EBV can cause splenic rupture, thrombocytopenia, agranulocytosis, hemolytic anemia and hemophagocytic lymphocytosis while HPV-B19 can cause severe aplastic crisis, stroke, nephrotic syndrome, myocardial infarction and splenic sequestration. Coinfection with EBV and HPV-B19 has not been reported in SCD patients and there are no reports of EBV or HPV B19 causing septic shock. A 15 year old male with SCD presented with a one day history of fever, oliguria, and hypotension caused by simultaneous viremia with EBV and HPV-B19. He had been discharged 2 days previously after an admission for a vaso-occlusive crisis. He did not have pharyngitis, rash hepatosplenomegaly (spleen likely autoinfarcted) or lymphadenopathy. Peripheral smear did not show lymphocytosis, atypical lymphocytes or features of microangiopathic hemolytic anemia. Fluid resuscitation with normal saline and then with red cell transfusion was done and he was transferred to pediatric intensive care unit. He received supportive therapy for septic shock with fluids, antibiotics and red cell transfusions. Blood and urine bacterial cultures were negative and blood quantitative DNA PCR was positive for EBV (3300 copies/ml) and HPV-B19 (2.3×107 copies/ml). His EBV titers were positive for viral capsid antigen (VCA)-IgM and IgG and Epstein Barr nuclear antigen (EBNA)-IgG. He had EBV titers done 2 years previously which were positive for VCA-IgG and EBNA-IgG documenting previous primary EBV infection. The patient gradually improved with supportive therapy and was discharged on Day 8. The patient returned to Pediatric Hematology clinic on Day 19 and had resolution of signs and symptoms. Table 1 shows an overview of his blood counts and transfusion requirements.Table 1 Coinfection with EBV and HPV-B19 in healthy adults has rarely been reported. Severe aplastic anemia caused by EBV and HPV-B19 infections was reported in a previously healthy 22-year-old male. He was treated with immunosuppressive therapy followed by allogeneic bone marrow transplant (Kaptan K et al, Am J Hematol 2001). Acute HPV-B19 infection and concomitant EBV reactivation causing moderate hemophagocytic syndrome was reported in a previously healthy 37-year-old-male (Larroche C et al, Eur J Clin Microbiol Infect Dis 2002). HPV-B19 infection with EBV reactivation has not been reported in children. Sepsis from viremia is not common with either EBV or HPV-B19, however together this co-infection can be life-threatening as seen in our patient. HPV-B19 infection has been reported to produce false positive EBV VCA-IgM serology assay. Our patient had a true coinfection because he had viremia documented by EBV DNA PCR. This is the first report of viremia and septic shock associated with an acute HPV-B19 infection and EBV reactivation in a patient with SCD. WBC- White Blood Cell Count, ANC- Absolute Neutrophil Count, ALC- Absolute Lymphocyte Count, Plt- Platelet Count, Hgb- Hemoglobin, HCT- Hematocrit, Retic: Corrected Reticulocyte Count, U- Units, PRBC- Packed red blood cells, ER- Emergency room Disclosures: No relevant conflicts of interest to declare.

2019 ◽  
Vol 32 (1) ◽  
pp. 78
Author(s):  
Andreia Sofia Costa ◽  
Anusca Paixão ◽  
Henrique Santos ◽  
Fernando Salvador

Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome, characterized by an excessive immune activation. It is triggered by multiple stimuli, with infections having an important role. The most common infectious trigger is viral infection, particularly by Epstein-Barr virus. Coagulation disorders are common in hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation can be present in severe cases. We report a clinical case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, complicated with disseminated intravascular coagulation which evolved favorably with only supportive therapy and without specific treatment.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Neda Hashemi-Sadraei ◽  
Pimprapa Vejpongsa ◽  
Muhamed Baljevic ◽  
Lei Chen ◽  
Modupe Idowu

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potential life-threatening clinical syndrome that results from uncontrolled activation of the immune system. Secondary HLH, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. Epstein-Barr virus (EBV) has been recognized as the leading infectious cause and is associated with a poor outcome. As clinical and laboratory features of HLH could overlap with septic shock syndrome in most patients, the diagnosis of HLH, especially in adults, is the most challenging aspect of the disease that results in delayed recognition and treatment of rapidly progressive multiorgan system failure. We report a case of Hemophagocytic lymphohistiocytosis in a patient who presented with signs of septic shock syndrome and we review the literature on the topic.


2015 ◽  
Vol 90 (2) ◽  
pp. 1129-1138 ◽  
Author(s):  
XueQiao Liu ◽  
Jeffrey I. Cohen

ABSTRACTEpstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-κB promoter activity in AP-1– and NF-κB–luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-κB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N-terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production.IMPORTANCEEpstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency.


2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Giorgio Berlot ◽  
Ariella Tomasini ◽  
Lorenzo Zandonà ◽  
Eugenio Leonardo ◽  
Rossana Bussani ◽  
...  

The authors describe the case of a young woman who developed a clinical pictures resembling a septic shock-related multiple organ dysfunction syndrome a couple of months after having been diagnosed suffering from a hemophagocytic lymphohistiocytosis associated with an infectious mononucleosis. Despite the aggressive treatment, which included antibiotics, vasopressors, IV immunoglobulins, and the use of an extracorporeal device aimed to remove mediators released both during sepsis and the cytokine storm determined by the hemophagocytic lymphohistiocytosis, the patient died. At the autopsy, an extremely uncommon aggressive lymphoma of Epstein-Barr virus-positive T-lymphocytes with systemic involvement was discovered.


2021 ◽  
Author(s):  
Neeraj Sharma ◽  
Rajat Shukla ◽  
Rachna Warrier ◽  
Kunal Kumar ◽  
Nalin Singh ◽  
...  

Abstract Pancytopenia is a condition when person has low count of all three types of blood cells causing a triage of anemia, leukopenia and thrombocytopenia. It should not be considered as a disease in itself but rather the sign of a disease that needs to be further evaluated. Among the various causes, viral infections like Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr virus and Parvovirus B19 have been implicated. Pancytopenia is a rare complication and not commonly seen in patients with COVID 19 disease. Here, we report a case of pancytopenia in previously immunocompetent elderly male patient with SARS-CoV2 infection.


2020 ◽  
Vol 20 (Suppl 2) ◽  
pp. s38-s38
Author(s):  
Faisal Rehman ◽  
Yahya Makkeyah ◽  
Abdul-Aema Buraq ◽  
Georgina Aldous ◽  
Sohail Ahmad

2020 ◽  
pp. 1-10
Author(s):  
Jaap M. Middeldorp ◽  
Zlata Novalić ◽  
Sandra A.W.M. Verkuijlen ◽  
Astrid E. Greijer ◽  
Jaap M. Middeldorp

Background: Epstein-Barr virus associated gastric carcinoma (EBVaGC) is considered a distinct GC disease entity, with the virus persisting in a latent phase. Treatment with Epirubicin, Capecitabine and Cisplatin (ECC combination) showed survival benefit in patients with GC in clinical trials (MAGIC study and CRITICS study) when compared to chemotherapy with Capecitabine and Cisplatin (GCb/Cis). Current treatment protocols for GC do not consider virus involvement. Methods: In this study, we tested a CytoLytic Virus Activation (CLVA) strategy consisting of the ECC combination or GCb/Cis together with the HDAC inhibitor Valproic acid (VPA) to define whether EBV reactivation and subsequent antiviral treatment with Ganciclovir (GCV) could be used as virus-targeted therapy for EBVaGC. Drug combinations with VPA and GCV were evaluated in multiple cell lines and in an EBVaGC mouse model based on human naturally EBV-infected SNU-719 cells. Results: EBV reactivation was demonstrated by lytic mRNA transcripts and proteins in treated cells, and the virus-reactivating capacity of different CLVA drug combinations was compared in C666.1, AGS-BX1 and SNU-719 cell lines. In an EBVaGC mouse model, GCb/Cis with VPA and GCV strongly reduced tumor volume and showed the highest potential for EBV-reactivation. Upon a single round of CLVA treatment, EBV DNA levels in circulation decreased, and loss of EBV-positive cells in treated tumors was observed. In vivo EBV-reactivation was revealed by the presence of lytic gene transcripts and proteins in tumor tissues 6 days after treatment. Conclusion: In EBVaGC model systems, CLVA treatment showed a more potent virus reactivation and killing of tumor cells when compared to standard chemotherapy alone, suggesting that addition of VPA plus GCV to the ECC or GCb/Cis combination should be considered in future clinical studies.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yun Xie ◽  
Song Cao ◽  
Hui Dong ◽  
Hui Lv ◽  
Xiaolei Teng ◽  
...  

Abstract Background Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation. Method This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data. Results Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group. Conclusions In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.


2020 ◽  
Author(s):  
Sandeep Chakraborty

Metagenomic studies of Covid19 patient sequencing data from different countries (China, Brazil, Peru, Cambodia, USA) shows a pattern that SARS-Cov2 enables anaerobic bacteria (eg Prevotella, Veil- lonella, Capnocytophaga, Fusobacterium, Oribacterium and Bacteroides) colonize the lungs, disrupting the homeostasis found in healthy patients. Long drawn symptoms in Covid19 have caused great con- sternation, and could be explained by persistence of biofilms. Some of these bacteria are implicated in increasing IL-6, cause ground glass opacity in lungs and are associated with cardiac injury - all symp- toms associated with Covid19. Many studies also show several bacterial infection markers - like D-dimer, LDH, C-reactive protein and ferritin - being significantly high, while the viral immune response is at- tenuated (reported by three studies till date). This is also confirmed here in the lung sample from a 74 year old deceased patient, showing high levels of IFITM3, ferritin and S100 calcium binding protein. Anaerobic bacteria causing initial symptoms like persistent fever, chills, pain and later symptoms like ARDS, blood clots, arterial stroke and septic shock finds resonance in a ”forgotten disease” - Lemierre syndrome (LS). While, LS is enabled by Epstein Barr Virus - possibly by ‘a transient depression of T cell immunity’, two recent studies show that IFN-λ might promote bacterial superinfection in Covid19. Also, 16S rRNA bacterial genes and endotoxins (LPS) were discovered in 18/19 severely ill pneumonia patients in one study, suggesting dissemination of endotoxins, and not actual bacteria, might suffice to cause severity. Autopsies also show foci of acute bronchopneumonia. There are key differences with LS - for example origin of LS is the jugular vein while Covid19 starts in the lungs (and this difference should result in Covid19 to be easier to treat). Co-infection of EBV and SARS-Cov2 leads to greater symptoms (fever, higher CRP) in a study of 67 patients. SARS-2003 showed a lot of similar symptoms, which did not get enough media attention. There was a specific warning issued in 2004 for ‘an increased vigilance against stroke and other thrombotic complications among critically-ill SARS patients in future outbreaks’. Enhanced pathogen testing kits, which include RT-PCT for bacterial genes and endotoxin tests, could confirm this disruption in Covid19, and thus anaerobic-specific antibiotics could significantly help in therapy.


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