Human Herpesvirus 6-A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation?

Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80-90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection-primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis.

Etiology and Multi-Drug Resistant Profile of Bacterial Infections in Severe Burn Patients, Romania 2018-2022.

Infections in severe burns and their etiology are and will remain a big concern for the medical field. The multi-drug resistant strains of bacteria are a challenge of today's medicine. The aim of our study was to identify the etiological spectrum of bacterial infections in severe burn patients in Romania and their multi-drug resistant patterns. We performed a prospective study that included 202 adult patients admitted to the intensive care unit (ICU) of the Clinical Emergency Hospital of Plastic, Reconstructive Surgery and Burns, Bucharest, Romania (CEHPRSB), from 1 October 2018 to 1 April 2022, a period which includes the first 2 years of the outbreak of COVID-19. From each patient, wound swabs, endotracheal aspirates, blood for blood culture, and urine were collected. The most frequently isolated bacterium was Pseudomonas aeruginosa (39%), followed by Staphylococcus aureus (12%), Klebsiella spp. (11%), and Acinetobacter baumannii (9%). More than 90% of Pseudomonas aeruginosa and Acinetobacter baumannii were MDR, regardless of the clinical specimen from which they were isolated.

Predictors of Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection.

Background and Objectives: SARS-CoV-2 infection is frequently associated with pneumonia but has a broad tissue tropism also leading to systemic complications (hematologic, gastro-intestinal, cardiac, neurologic, etc.). In this study, we aim to evaluate the impact of COVID-19 infection on the liver and to identify the risk factors/predictors for liver injury at admission to the hospital. Materials and Methods: We performed a retrospective cohort study on 249 patients, divided into two Group A (157 patients with liver involvement) and Group B (92 patients without liver involvement). We recorded demographic and lifestyle parameters, anthropometric parameters, comorbidities, clinical parameters, inflammation markers, complete blood count, coagulation, and biochemical parameters. Lung parenchyma, liver dimensions, and morphology were evaluated by computer tomography (CT) scans. Results: Patients with liver involvement had higher heart and respiratory rates, lower oxygen saturation (SO2), and necessitated higher oxygen flow at admittance. We found higher serum levels of C-reactive protein, fibrinogen, ferritin, creatine kinase, lactate dehydrogenase (LDH), serum triglycerides, and lower values for serum albumin in Group A patients. The patients with liver involvement presented more extensive lung injury with higher percentages of alveolar, mixed, and interstitial lesions, an increase in liver dimensions, and lower density ranges for the liver parenchyma. The patients presented hepatocytolytic involvement in 26 cases (10.4% from the entire study population), cholestatic involvement in 63 cases (37.7% from the entire study population), and mixed liver involvement in 68 cases (37.7% from the entire study population). Conclusions: Liver involvement in COVID-19 patients is frequent, usually mild, and occurs mostly in male patients over 50 years old. Cholestatic and mixed liver injuries are more frequent than hepatocytolytic injuries. The severity of lung injury evaluated by CT scan, increased values of inflammatory markers, LDH, and low values of SO2 can be considered risk factors/predictors for liver injury at admission to the hospital.

Interstitial Lung Fibrosis Following COVID-19 Pneumonia.

Background and Objectives: Pulmonary fibrosis represents a stage of normal physiologic response to inflammatory aggression, mostly self-limiting and reversible; however, numerous patients treated for SARS-CoV-2 pneumonia present after release from hospital residual lung fibrosis. In this article, we aim to present an optimization method for evaluating pulmonary fibrosis by quantitative analysis, to identify the risk factors/predictors for pulmonary fibrosis in patients with SARS-CoV-2 infection, and to characterize the impact of pulmonary fibrosis on the symptomatology of patients after release from the hospital. Materials and Methods: We performed a prospective observational study on 100 patients with severe forms of pneumonia, with a control group of 61 non-COVID normal patients. Results: We found persistent interstitial changes consistent with fibrotic changes in 69% of patients. The risk of fibrosis was proportional to the values of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and lactate dehydrogenase (LDH), and to the duration of hospitalization. The imaging parameters correlated with increased risk for interstitial fibrosis were the number of affected pulmonary lobes and the percent of interstitial pulmonary fibrosis. Conclusions: The main risk factors for pulmonary fibrosis post-COVID-19 identified in our study are increased ESR, CRP, LDH, duration of hospitalization and the severity of pneumonia.

Anticoagulant Therapy in Sepsis. The Importance of Timing.

Sepsis associated coagulopathy is due to the inflammation-induced activation of coagulation pathways concomitant with dysfunction of anticoagulant and fibrinolytic systems, leading to different degrees of haemostasis dysregulation. This response is initially beneficial, contributing to antimicrobial defence, but when control is lost coagulation activation leads to widespread microvascular thrombosis and subsequent organ failure. Large clinical trials of sepsis-related anticoagulant therapies failed to show survival benefits, but posthoc analysis of databases and several smaller studies showed beneficial effects of anticoagulants in subgroups of patients with early sepsis-induced disseminated intravascular coagulation. A reasonable explanation could be the difference in timing of anticoagulant therapy and patient heterogeneity associated with large trials. Proper selection of patients and adequate timing are required for treatment to be successful. The time when coagulation activation changes from advantageous to detrimental represents the right moment for the administration of coagulation-targeted therapy. In this way, the defence function of the haemostatic system is preserved, and the harmful effects of overwhelming coagulation activation are avoided.

Sepsis-Associated Coagulopathy.

Systemic inflammatory activation in sepsis often leads to coagulation activation, but the relationship is bilateral, as coagulation also modulates the inflammatory response. This close associate has significant consequences for the pathogenesis of microvascular thrombosis and organ dysfunction in sepsis. While coagulation activation can be beneficial for immune defense, it can also be detrimental once it becomes widespread and uncontrolled. The knowledge of the pathophysiologic mechanisms involved in the interaction between infection and coagulation may lead to the better timing for the administration of targeted antithrombotic therapies in septic patients. This brief review highlights the pathophysiologic pathways leading to the prothrombotic state in sepsis and the mechanisms that play a role in the interaction between infection and coagulation.

Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV--a survival analysis.

To investigate whether asymptomatic cytomegalovirus (CMV) viraemia impact the course of human immunodeficiency virus (HIV) infection, this study evaluated the effect of CMV replication on progression of newly-diagnosed HIV infected individuals towards AIDS events and death. In a 3-year prospective study on co-infected patients, clinical, immunological, and virological tests were performed in a national reference hospital quarterly. CMV viraemia was quantified by RoboGene® HCMV DNA Quantification Kit (Analytik Jena, Germany), on ABI Prism® 7000 Sequence Detection System (Applied Biosystems, USA). One hundred and five patients were enrolled with a balanced sex distribution and a median age of 30.7 years. Median CD4(+) cell count at enrollment was 164/mm(3) and median HIV RNA 4.6 log10 copies/ml. Detectable CMV viraemia was found in 25.7% of the patients. Kaplan-Meier analysis showed progression of HIV infection to be significantly increased in those with active CMV replication and/or low CD4(+) cell count. Cox regression indicated the risk of developing new AIDS events was 2.6 times greater in patients with detectable CMV viraemia versus those without (CI95% 1-6.6; P = 0.04). Also in multivariate analysis, the overall risk of progression to AIDS events or death was 3-fold higher in those with detectable CMV viraemia (CI95% 1.3-6.7; P = 0.008) and 2.3-fold higher if CD4(+) cell count was below 100/mm(3) (CI95% 1-5.1; P = 0.04). In these young Romanian HIV-seropositives, active CMV replication increased morbidity, even when treated with combination antiretroviral therapy. Further studies are needed to evaluate if serial quantitative CMV-DNA levels might correlate with non-infectious inflammation-related risks in patients with HIV and active CMV infection.

The impact of hepatitis viruses on chronic lymphoproliferative disorders--preliminary results.

UNLABELLED: The aim of this study is to analyze a group of patients with chronic lymphoproliferative disorders associated with B, C, D hepatitis viral infection. This group of chronic lymphoproliferative disordered patients with associated hepatitis viral infection has been diagnosed and monitored in the Hematology Department of the University Emergency Hospital of Bucharest, between December 2007 and January 2009. Our study is meant to observe the influence of the viral infection on clinical and biological evolution of the enrolled patients. The diagnosis of the chronic lymphoproliferative disorder was based on the bone marrow/ lymph node biopsy and flow-cytometry analysis. The positive diagnosis for hepatitis viral infection was established by ELISA serological tests and viremia was performed by TaqMan method at INBI "Matei Bals" Bucharest. The analyzed group is made up of 41 patients, 25/41 (60.97%) females and 16/41 (39.02%) males, with ages: 20-50 years old--6/41 (14.63%), 51-70 years old--23/41 (56.09%) and over 71 years old--12/41 (29.26%) patients. The histological types of CLD: B-cell non-Hodgkin's lymphoma--in 28/41 (68.29%) patients, T-cell non-Hodgkin's lymphoma--2/41 (4.87%) patients, Hodgkin's lymphoma--2/41 (4.87%), chronic lymphocytic leukemia--7/41 (17.07%), Waldenström disease--2/41 (4.87%) patients. Regarding the type of CLD, 19/41 (46.34%) of the patients have an aggressive type of CLD and 22/41 (53.65%) a non-aggressive type of CLD. The hepatitis viral infection distribution in our patients: 14/41 (34.14%) have HBV infection, 24/41 (58.53%) have HCV infection, double/triple association of viral infection was found in 3/41 (7.31%) patients. Within HBV infection subgroup 9/14 (64.28%) patients have an aggressive type of CLD and 5/14 (35,71%) patients have a non-aggressive type, whereas within the group with HCV infection we found a different distribution: 9/24 (37,5%) patients with aggressive type and 15/24 (62.5%) with non-aggressive type of CLD. The clinical parameters monitored were: B signs were present in 19/41 (43.34%) patients, the superficial or profound adenopathies--were found in 29/41 (70,73%) patients, hepatomegaly--in 38/41 (92,68%) patients, splenomegaly--in 21/41 (51.21%) patients, extra-nodal involvements in 10/41 (24,39%) patients and most frequent in the non-aggressive type of CLD--6/10 (60%) patients. The hematological and biochemical parameters were: the presence of anemia and thrombocytopenia--found in a small number of patients; lymphocytosis--positive in 33/41 (80.48%) patients, most with HCV infection and non-aggressive type of disease, the presence of autoimmune hemolytic anemia--in 4/41 (9.75%) patients, cryoglobulins--8/41 (19.51%) patients, all with HCV infection; also the liver function was monitored. Antiviral therapy was administered to 12/41 (29.26%) patients--Lamivudine to 8/41 (19.51%) patients and Ribavirine/Interferon to 4/41 (9.75%) patients. Chemotherapy was given in 32/41 (78%) patients. Monoclonal antibodies anti CD20 (Rituximab) therapy was associated in 6/41 (14.63%) patients. CONCLUSIONS: A high incidence in female sex of over 50 years old was noticed. A strong association between B-cell chronic lymphoproliferative disorders and hepatitis viral infection B, C, D was revealed, the most frequent being the C hepatitis virus, associated with the non-aggressive type of CLD, extra-nodal involvement, splenomegaly, lymphocytosis, cryoglobulins, cytolysis and colestasis. The clinical and biological disease history will be monitored during chemotherapy and antiviral treatment.

Seroprevalence and risk factors associated with herpes simplex virus infection among pregnant women.

OBJECTIVES: To estimate the type-specific seroprevalence and identify the risk factors associated with herpes simplex virus (HSV)-2 infection in pregnant women in Bucharest, Romania. METHODS: A prospective survey was conducted in 452 subjects, aged 15-39 years, at the Elias Hospital, during the years 2004-2005. We evaluated serum IgG anti-bodies to HSV-1 and HSV-2 using the HerpeSelect ELISA test. All subjects completed an epidemiological questionnaire. RESULTS: Seroprevalence was 87.3% and 15.1% for HSV-1 and HSV-2, respectively. The risk factors for HSV-2 infection were lower level of education and a greater number of sexual partners. Elementary school and high-school graduates were 6.28 and 2.26 times more exposed than University graduates. Having 2-3 partners and more than three partners was associated with 2.43 and 4.26 times the risk of acquiring HSV-2, compared with having one partner. CONCLUSIONS: In pregnant women, HSV-1 seroprevalence was higher than in Western Europe but similar to that in Eastern Europe. HSV-2 seroprevalence was within European ranges. Both were lower than in the USA. Risk factors for HSV-2 infection may lead to prevention programs.