Risk of Hepatitis B Virus Reactivation in COVID-19 Patients Receiving Immunosuppressive Treatment: A Prospective Study.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients.

Pericardial and Pleural Effusions in Non-ICU Hospitalized Patients with COVID-19-A Retrospective Single-Center Study.

Background: Pericardial and pleural effusions are two complications recently described in patients hospitalized with COVID-19 infections. There are several mechanisms that have been proposed and refer to SARS-CoV-2's capacity to bind to cell surfaces via various receptors and its broad tissue tropism that might cause significant complications. The aim of the present study is to evaluate the incidence of pericardial and pleural effusions during COVID-19 infection as well as to determine the risk factors associated with these complications. Methods: We conducted a retrospective single-center study that included 346 patients admitted to the National Institute of Infectious Disease "Prof. Dr. Matei Bals" (Bucharest, Romania), from 1 January to 25 May 2021, during the third wave of the pandemic. Socio-demographic and anthropometric data were collected for each patient. The patients were evaluated clinically, biologically, and radiologically within 48 h of admission. Patients were divided into 3 groups: (1) patients with pericardial effusions-18; (2) patients with pleural effusions-28; (3) patients without pericardial/pleural effusions-294. Results: After exclusion criteria were applied, 337 patients were analyzed. The median age of the participants was 58.26 ± 14.58 years. More than half of the hospitalized patients had associated respiratory failure (61.5%), of which 2.7% had a critical form of the disease and 58.8% had a severe form. The cumulative percentage for pericardial and pleural effusions for the study group was 12.8% (43 patients out of 337). The prevalence of pericardial effusion was 5.3%, twice more frequent among male respondents. Pleural effusion was identified in 8.3% patients. Most patients had unilateral effusion (17), compared to 11 patients who had bilateral involvement. Based on laboratory results, patients with pericardial and pleural effusions exhibited increased levels of C reactive protein, erythrocyte sedimentation rate, NT proBNP, and a higher value of neutrophil/lymphocyte count ratio. In contrast to patients without pleural and pericardial effusions, those with these symptoms experienced a higher frequency of severe or critical illness and longer hospital stays. Conclusions: Pericardial and pleural effusions can complicate COVID-19 infections. In our study, the prevalence of pericardial and pleural effusions in hospitalized patients was low, being associated with the same comorbidities and a number of clinical and biological parameters.

Hepatitis B and C Virus Reactivation Patterns in a Romanian Cohort of Patients with Chronic Lymphoproliferative Disorders.

Hepatitis B and C virus (HBV and HCV) reactivations have become more common following the intensive use of biological therapies for the treatment of chronic lymphoproliferative disorders (CLD). We evaluate risk factors for virus reactivation and exitus in patients diagnosed with CLD and HBV or HCV infection, undergoing rituximab-chemotherapy (R-chemo). A prospective, observational study in two tertiary-care Romanian hospitals, between December 2007 and May 2010, of patients diagnosed with CLD undergoing R-chemo. HBV and HCV serological markers, viral load, fibrosis and necroinflammation were assessed at baseline and every 3-6 months. We screened 502 patients diagnosed with CLDs (77.2% non-Hodgkin lymphomas) and enrolled 57 patients with HBV and/or HCV infection with a mean age of 61.35 ± 11.1 years. The replicative virus was HBV in 23 patients (40.3%), HCV in 33 patients (57.9%). HCV reactivation rate (15.6%) was lower than for HBV (45.5%) (p = 0.02). In univariate analysis, viral reactivation was associated with aggressive CLD (p = 0.01), HBV (p = 0.01) and lymphopenia (p = 0.02). Death was associated with aggressive CLD (p = 0.01), viral reactivation (p = 0.001) and high baseline viremia (p = 0.05). In multivariate analysis, viral reactivation was associated with lymphopenia (OR 0.05, 95% CI 0.003-0.85, p = 0.03). Risk of death was 10 times higher for patients with viral reactivation (95% CI 1.54-65.5, p = 0.01). A quarter of the infected patients were diagnosed with viral reactivation. While hepatitis C was more prevalent than hepatitis B in patients with CLD, viral reactivation was found 3 times more frequently in patients with hepatitis B than C.

CccDNA persistence during natural evolution of chronic VHB infection.

HBV infection remains a public health issue. CccDNA-HBV is a unique, intermediate replicative episome, responsible for persistence of infection in hepatocytes. The clearance of cccDNA may be explained by cellular death. CccDNA detection in chronic infected human livers may represent an important marker in monitoring antiviral therapy. Short term therapy is followed by viral rebound in the majority of chronic HBV hepatitis patients. Based on mathematical models, it is considered that the period needed to achieve a complete intrahepatic cccDNA clearance is 14.5 years.

Preliminary data on the involvement of B, C and D hepatitis viruses in the etiopathogenesis of chronic lymphoproliferative syndromes in Romania.

UNLABELLED: THE AIMS OF THE STUDY: Evaluation of the prevalence of HBV, HCV, HDV infection in patients with chronic lymphoproliferative diseases (CL), identification of the most involved viral genotypes, correlation between viremia dynamics and CL evolution, detection of molecular mechanisms implicated in CL pathogenesis, identification of lymphocytic receptors for viral antigens and biologic markers for early diagnosis of CL. METHODS: We present preliminary results of the first year of our research grant. This is a prospective, analytic, observational study in patients diagnosed with CL and HBV, HCV, HDV chronic infection. We included the following forms of CL: non-Hodgkin malignant lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL). We used the following commercial test kits: HCV RNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 28 to 140.000.000 UI/ml detection range for HCV viremia, HBV DNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 6 to 110.000.000 UI/ml detection range for HBV and the Roboscreen-RoboGene AJ kit with 10-10.000.000 replica/ml detection range for HDV. RESULTS: We have included 20 patients with CL and chronic hepatitis infection so far. Median age of the patients was 61 years. The identified CL forms were: B cell NHL (15 cases), T cell NHL (1 case), CLL (3 cases), Hodgkin lymphoma (1 case), equally distributed in aggressive and indolent forms of CL. HCV infection was diagnosed in 10 patients with CL, HBV infection was found in 10 patients with CL, 3 of them having co-infection HBV + HDV. In 4 patients with HBV infection viremia was over 20.000 IU/ml and the pattern of the CL was the aggressive form of the disease. The feature of the co-infection HBV + HDV was the predominance of indolent forms of CL. Among patients with HCV infection, only 3 cases were detected with viremia over 600.000 IU/ml and CL was represented by aggressive forms of the disease. We also have immunohistochemical data available in 19 cases, which seem to confirm the role of hepatitis viruses in lymphoproliferative disease etiopathogenesis. CONCLUSIONS: We ascertained an almost equally represented prevalence of HCV and HBV infection in patients with CL. The levels of HBV, HCV and HDV viremia were low in most of the cases. The most frequent form of CL was B cell NHL. We found an equal distribution between indolent and aggressive forms of NHL associated to hepatitis virus infection.