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.

Replacement Therapy with Blood Products in People Living with HIV.

Cytopenias or coagulation deficiencies can occur in people living with HIV (PLWH). The severity of these disorders is influenced by the low levels of CD4+ lymphocytes, viral load, and the stage of viral infection. The aim of our retrospective observational study was to determine the frequency of cytopenias and coagulation deficiencies in PLWH as well as the need for replacement therapy with blood products. We sought to determine whether there is an association between severe anemia or thrombocytopenia (requiring replacement therapy) and CD4+T lymphocyte levels. All 29 patients were critically ill, with 27 out of 29 (93%) in advanced stages of HIV disease and 23 out of 29 (79%) having CD4+ lymphocyte counts below 200 cells/microL. Most patients were either late presenters (45%) or had been lost to follow-up (41%). In addition to HIV infection, various conditions that could alter hematologic parameters were associated, including co-infections with hepatitis viruses, tuberculosis at various sites, malignant diseases, sepsis, SARS-CoV-2 infection, or other opportunistic infections. No significant correlation was found between severe anemia or severe thrombocytopenia or coagulation deficiencies and the CD4+T lymphocyte count. Our data suggest that these hematological disorders in patients with advanced HIV infection are more likely to be associated comorbidities rather than the HIV infection per se.

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.

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.

Ocular involvement in highly treatment-experienced patients with HIV.

Introduction: Ocular involvement in human immunodeficiency virus (HIV) infected and treatment-experienced patients is a significant concern, despite the advancements in antiretroviral therapy (ART) medication. The extended life expectancy of HIV patients has altered the spectrum of HIV-associated ocular diseases, ranging from minor issues to severe vision impairment or blindness. Therefore, understanding these complications becomes crucial in providing comprehensive medical care and quality of life improvement. HIV patients on multiple ARTs can experience various ocular disorders due to the complexity of their treatment regimens, drug toxicities, immune reconstitution, and opportunistic infections. Most worthy to consider are: cytomegalovirus (CMV) retinitis, immune recovery uveitis (IRU), keratoconjunctivitis sicca (dry eye syndrome), and HIV-associated neuroretinal disorders. Materials and methods: A retrospective clinical investigation was conducted on HIV/AIDS-infected patients from January 1, 2013, to December 31, 2023. The study included 62 patients over 18 years, who tested HIV-positive via enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot (WB), with assessments of HIV plasma viral load (VL) and CD4+ T cell counts (CD4). Data collected included demographics, pathological histories, clinical characteristics, blood tests, assessments for opportunistic infections, patient staging, antiretroviral therapy initiation, and disease prognosis. Results: The study found that of most patients, 37 were aged 30-39 (59.7%), with 59.7% males and 40.3% females. Most had been living with HIV for 10-19 years (35.5%). Initial CD4 counts were < 200 cells/mm3 in 46.8% of patients, which improved to 19.3% when the study was done. CMV retinitis prevalence decreased from 46.8% initially to 35.5% despite ART. Other conditions included ocular toxoplasmosis (3.22%), tuberculosis-related uveitis (1,6%), keratoconjunctivitis sicca (19.3%), and HIV retinopathy (29%). Notably, 62.1% of CMV retinitis patients experienced significant visual acuity reduction. Oral valganciclovir was beneficial for patients with CMV disease affecting multiple sites and effective for both induction and maintenance therapy of CMV retinitis. Conclusions: Managing ocular complications in HIV-experienced patients requires a multidisciplinary approach with regular ophthalmologic evaluations, prompt treatment of infections, and continuous monitoring of ART effectiveness. Early detection and intervention are crucial for preserving vision and improving outcomes. The study highlighted the importance of constant monitoring even after viral suppression. Abbreviations: HIV = Human immunodeficiency virus, ART = antiretroviral therapy, CMV = cytomegalovirus, IRU = immune recovery uveitis, ELISA = enzyme-linked immunosorbent assay, WB = Western Blot, VL = viral load, CD4 = CD4+ T cells.

Miscellaneous ophthalmic conditions related to low CD4 cell count in HIV-positive patients.

Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei Balș" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy.

Influenza Vaccination of Romanian Medical Students during COVID-19 Times: From Knowledge to Behavior.

In Romania, influenza vaccination uptake among healthcare workers decreased over time despite access to the vaccine being constantly improved. The aim of this paper is to provide a comparative analysis of the knowledge and attitudes of Dental Medicine and Medicine students towards recommended vaccinations for healthcare workers, focusing on influenza vaccination. A cross-sectional study was conducted during the entire 2021-2022 academic year. Data were collected using 2 electronic questionnaires which were applied to the students from the Faculty of Medicine (n = 883) and, respectively, the Faculty of Dental Medicine of the Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. The questionnaires were offered to 1187 students and completed by 911 students (response rate = 77%). Out of these, 85% (n = 778) identified the influenza vaccine as recommended; 35% (n = 321) reported getting an annual influenza vaccination; and 37% (333) reported getting an influenza vaccination in the previous season. Overall, 45% (n = 222) of the respondents who completed the questionnaires from October 2021 to February 2022 reported that they intend to get vaccinated against influenza in the 2021-2022 season and approximately 8% (n = 39) reported that they had already been vaccinated. The multivariable analysis showed that the habit of getting annually vaccinated against influenza as well as the knowledge that influenza vaccine is recommended for all healthcare workers were associated with a higher probability of intending to get vaccinated. The current study emphasizes the need to raise awareness among medical students regarding influenza vaccination and to involve medical education institutions, public health authorities, and healthcare facilities in promoting this vaccination among students since the influenza vaccine uptake rate among medical students included in this study was suboptimal.

Hybrid Immunity and the Incidence of SARS-CoV-2 Reinfections during the Omicron Era in Frontline Healthcare Workers.

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 infections, vaccination, and the dominant variant of SARS-CoV-2 in the population. We collected and analyzed data using the χ2 test and density incidence of reinfections in Microsoft Excel for Mac, Version 16.84, and MedCalc®, 22.026. Of the 829 HCWs, 70.1% (581) had only one SARS-CoV-2 infection and 29.9% (248) had two infections. Of the subjects with two infections, 77.4% (192) worked in high-risk departments and 93.2% (231) of the second infections were registered during Omicron dominance. The density incidence of reinfections was higher in HCWs vaccinated with the primary schedule than those vaccinated with the first booster, and the incidence ratio was 2.8 (95% CI: 1.2; 6.7). The probability of reinfection was five times lower (95% CI: 2.9; 9.2) in HCWs vaccinated with the primary schedule if the first infection was acquired during Omicron dominance. The subjects vaccinated with the first booster had a density incidence of reinfection three times lower (95% CI: 1.9; 5.8) if the first infection was during Omicron. The incidence ratio in subgroups constructed based on characteristics such as gender, age group, job category, and department also registered significant differences in density incidence. The history of SARS-CoV-2 infection by variant is important when interpreting and understanding public health data and the results of studies related to vaccine efficacy for hybrid immunity subgroup populations.

Investigation of Serum Endocan Levels in SARS-CoV-2 Patients.

Endocan is an endothelial-cell-specific proteoglycan (ESM-1) and has emerged as an endothelial dysfunction and inflammatory marker in recent years. Endocan can be used as a marker of inflammatory endothelial dysfunction in endothelium-dependent disease: cardiovascular disease, sepsis, lung and kidney disease and malignancies. Recent data suggest that endothelial dysfunction is a key mechanism in COVID-19 pathogenesis. Endotheliitis and thrombo-inflammation are associated with severe forms of SARS-CoV-2 infection, and endocan is currently under investigation as a potential diagnostic and prognostic marker. The aim of this study was to determine serum endocan levels in patients with COVID-19 to evaluate the correlation between endocan levels and clinical disease diagnosis and prognosis. This study enrolled 56 patients, divided into three groups depending on disease severity: mild (15), moderate (25) and severe (16). The biochemical, demographic, clinical and imagistic data were collected and evaluated in correlation with the endocan levels. Serum endocan levels were significantly higher in the COVID-19 patients compared to the control group; also, endocan concentration correlated with vaccination status. The results revealed significantly elevated serum endocan levels in COVID-19 patients compared to the control group, with a correlation observed between endocan concentration and vaccination status. These findings suggest that endocan may serve as a novel biomarker for detecting inflammation and endothelial dysfunction risk in COVID-19 patients. There was no significant relationship between serum endocan levels and disease severity or the presence of cardiovascular diseases. Endocan can be considered a novel biomarker for the detection of inflammation and endothelial dysfunction risk in COVID-19 patients.

The Impact of Obesity on the Host-Pathogen Interaction with Influenza Viruses - Novel Insights: Narrative Review.

After exposure to a viral pathogen, the host-pathogen interaction is essential to determine whether or not infection will ensue, and what the clinical outline of the infection will be. Recent research has shown that the patient with obesity presents a set of particular pathophysiological changes that lead to higher severity of viral infections, and this is particularly true for infection with influenza viruses. Herein, we describe the main metabolic, endocrine, and immune dysregulations that occur in the presence of obesity and their impact on driving intra-host viral diversity, leading to heightened severity and virulence of influenza. We show that obesity is linked to modified responses of both the innate and adaptive immune systems during viral infections, including influenza. Due to chronic inflammation and metabolic, endocrine, and signaling pathway disruptions, individuals with obesity have a suboptimal immune response. This results in longer illness duration, increased virus shedding, higher risk of hospitalization and complications, and greater mortality rates. Additionally, they may have a blunted response to vaccination and a higher likelihood of genetic mutation selection. Understanding the intricate interplay between obesity and viral pathogenesis is crucial for developing efficacious therapeutic approaches and public health policies, particularly in light of the escalating worldwide incidence of obesity.

The Dynamic Risk of COVID-19-Related Events in Vaccinated Healthcare Workers (HCWs) from a Tertiary Hospital in Bucharest, Romania: A Study Based on Active Surveillance Data.

Our study describes the frequency and severity of COVID-19 in HCWs and estimates the dynamic risk of COVID-19-related events. We actively surveyed all HCWs from a tertiary infectious disease hospital from 26 February 2020 to 31 May 2023. Of 1220 HCWs, 62.9% (767) had at least one COVID-19 episode. The under 29 years (p = 0.0001) and 40-49 years (p = 0.01) age groups, nurses (p = 0.0001), and high-risk departments (p = 0.037) were characteristics significantly more frequent in HCWs with COVID-19 history. A higher percentage of boosters (53.2%; p < 0.0001) were registered in the uninfected group. The second episode of COVID-19 was significantly milder than the first. Data regarding clinical outcomes from 31 January 2021 to 31 May 2023 were analyzed in a follow-up study to determine the risk of COVID-19-related events. The Cox regression analysis revealed that HCWs with booster shots had a lower risk of COVID-19 across all events, symptomatic events, and moderate to severe events as adjusted hazard ratio (aHR) were: 0.71 (95%CI: 0.54-0.96), 0.23 (95%CI: 0.12-0.46), and 0.17 (95%CI: 0.07-0.43), respectively. Within the vaccinated subgroup, the HCWs with hybrid immunity and booster had aHR for all followed-up events of 0.42 (95%CI: 0.30-0.58), for symptomatic events of 0.52 (95%CI: 0.36-0.74), and 0.15 (95%CI: 0.03-0.66) for moderate to severe events. The risk of COVID-19 clinical events was lower for HCWs with at least one booster than those completely vaccinated.

Ophthalmological Manifestations in People with HIV from Northeastern Romania.

Background and Objectives: Although ocular disorders can occasionally impact people with HIV over the course of their illness, HIV/AIDS is unmistakably a multisystem disorder. A physician can rule out a wide range of ophthalmic problems with the assistance of an ophthalmologist, from adnexal disorders to posterior segment diseases, including those affecting the optic tract and optic nerve. Materials and Methods: Based on patient medical data from the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi, we carried out a retrospective clinical investigation on patients with HIV/AIDS and ophthalmological conditions who were hospitalized in northeastern Romania. We seek to draw attention to the characteristics and ophthalmological comorbidities of HIV/AIDS patients. The studied period was between 1 January 1991 and 31 December 2022. Results: There were a total of 38 recorded cases of ophthalmological manifestations in the HIV-infected patients. The research group's average age was 37.31 years old (standard deviation 9.5693917). Males were primarily impacted, having lower total CD4+ T-lymphocyte levels based on sex and CD4+ T-lymphocyte levels overall. The HIV viral load was 999 268.13 copies/mL on average (standard deviation 1,653,722.9). Of all the patients, we found out that 17 had congenital eye diseases (44.73%) and the others (21, 55.26%) developed ophthalmological diseases. CMV Retinitis was found most frequently, in eight patients (21.05%), followed by Myopia in seven patients (18.42%). Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach and access to antiretroviral therapy. Anyone who is HIV-positive and experiences ocular symptoms at any time should be directed to seek professional ophthalmologic treatment as soon as feasible. A therapeutic holdup could result in irreversible vision loss. Long-term coordination is required to combat this disease, improving communication between the ophthalmology and infectious disease fields.

Carbapenemase-producing uropathogens in real life: epidemiology and treatment at a County Emergency Hospital from Eastern Romania.

Urinary tract infections are a public health problem exacerbated by the rising concern of antibiotic resistance. Carbapenem-resistant Enterobacterales (CRE), mostly isolated from urine samples, represent an immediate public health threat, often associated with healthcare settings. This study investigated 27 cases of carbapenemase-producing organisms (CPO) detected in urinalysis over one year. There was a significant association between the presence of chronic indwelling urinary catheters and the temporary use of urinary catheters, with both groups accounting for 66.7% of all cases. We identified two modes of transmission for extended drug-resistant microorganisms: inter-hospital spread, covering wide geographical distances (involving four healthcare units across two other counties), and intra-hospital transmission (12 departments within our institution). Medium-size hospitals should thoroughly investigate their specific carbapenemase-producing strains. Their laboratories must be well-supplied to handle this situation and perform the necessary testing accurately. Treatment options should be available based on presumed susceptibility and antimicrobial susceptibility testing, with a range of antibiotics available, including novel agents such as Ceftazidime-avibactam, as well as established options like Aminoglycosides and Colistin. Adherence to rigorous catheter handling protocols, as emphasized by national and international guidelines, is essential and should be implemented consistently across all hospital departments.

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.

Vaccination and Factors Related to the Clinical Outcome of COVID-19 in Healthcare Workers-A Romanian Front-Line Hospital's Experience.

The study aims to describe the frequency of COVID-19 in healthcare workers (HCWs) in a designated hospital for COVID-19 treatment in Bucharest, Romania, and to explore COVID-19 vaccination and other factors associated with the clinical outcome. We actively surveyed all HCWs from 26 February 2020 to 31 December 2021. Cases were laboratory-confirmed with RT-PCR or rapid test antigen. Epidemiological, demographic, clinical outcomes, vaccination status, and co-morbidities data were collected. Data were analyzed using Microsoft Excel, SPSS, and MedCalc. A total of 490 cases of COVID-19 in HCWs were diagnosed. The comparison groups were related to the severity of the clinical outcome: the non-severe group (279, 64.65%) included mild and asymptomatic cases, and the potentially severe group included moderate and severe cases. Significant differences between groups were registered for high-risk departments (p = 0.0003), exposure to COVID-19 patients (p = 0.0003, vaccination (p = 0.0003), and the presence of co-morbidities (p < 0.0001). Age, obesity, anemia, and exposure to COVID-19 patients predicted the severity of the clinical outcomes (χ2 (4, n = 425) = 65.69, p < 0.001). The strongest predictors were anemia and obesity (OR 5.82 and 4.94, respectively). In HCWs, mild COVID-19 cases were more frequent than severe cases. Vaccination history, exposure, and individual risk influenced the clinical outcome suggesting that measures to protect HCWs and occupational medicine are important for pandemic preparedness.

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.

Evaluation of Drug-Induced Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection.

Elevated liver enzymes are frequently reported in SARS-CoV-2-infected patients. Several mechanisms of liver injury have been proposed, but no clear conclusions were drawn. We aimed to evaluate hepatocellular and cholestatic injury in relation to the administration of potentially hepatotoxic drugs included in the current COVID-19 therapeutic guidelines in a retrospective cohort of 396 hospitalized COVID-19 patients. The main findings of our study are: (1) Significant increase in aminotransferases level was observed during hospitalization, suggesting drug-related hepatotoxicity. (2) Tocilizumab was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal. (3) Anakinra was correlated with ALT values greater than three times the upper limit of normal. (4) Younger patients receiving tocilizumab or anakinra had a higher risk of hepatocellular injury. (5) The combination of favipiravir with tocilizumab was associated with AST values greater than three times the upper limit of normal and with an increase in direct bilirubin. (6) The administration of at least three potentially hepatotoxic drugs was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal, and with the increase in indirect bilirubin. (7) Remdesivir and favipiravir by themselves did not correlate with hepatocellular or cholestatic injury in our study cohort.

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.

The COVID-19 Pandemic in Romania: A Comparative Description with Its Border Countries.

The COVID-19 pandemic continues to be a major public health problem in most countries of the world, especially in developing countries with an underfunded healthcare system. We aim to present a comparative profile of the epidemiological characteristics of the COVID-19 pandemic in Romania and neighboring countries, which have similar onset and a similar socio-cultural pattern. A descriptive comparative study was performed using COVID-19 data collected from various official websites regarding demography, morbidity, mortality, vaccination, and testing capacity. The countries included in the study were Romania, Bulgaria, Hungary, Republic of Moldova, Serbia, and Ukraine. The study period was from week 09/2020 to week 46/2021. Overall, these countries have reported 8,382,441 cases and 216,014 deaths (during the study period). The highest cumulative incidence rate of cases has been recorded in Serbia (17,801.5) and the highest mortality rate has been recorded in Bulgaria (391.0). Romania is in fourth place regarding the cumulative incidence rate of cases/100,000 inhabitants but in third place regarding the mortality due to COVID-19 (case-fatality rate of 3.1%). Although the World Health Organization and EU co-ordinate the COVID-19 response, each state makes its own decisions regarding SARS-CoV-2 mitigation measures, the epidemiological indicators directing us about the effectiveness of responses.

Dynamics of APRI and FIB-4 in HCV cirrhotic patients who achieved SVR after DAA therapy.

There are limited data available on the regression of fibrosis in hepatitis C virus (HCV) patients who have achieved sustained virologic response (SVR) after interferon-free treatments. Moreover, a perfect method for assessing liver fibrosis and its dynamics has not been established yet. The main objective of this study was to evaluate the dynamics of aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores in patients with HCV who registered SVR. We performed ROC curve analysis to evaluate the diagnostic performance of APRI and FIB-4 scores in determining the presence of cirrhosis in comparison to FibroTest. In total 251 patients were enrolled: 164 cirrhotic and 83 non-cirrhotic patients, and they were evaluated at baseline, at 6 and at 12 months post-end of treatment (EOT). In the cirrhotic group, at baseline, there was a weak but statistically significant correlation between APRI and FibroTest (τ=0.173, P=0.001), as well as between FIB-4 and FibroTest (τ=0.265, P<0.001). At the 6-month follow-up, APRI no longer correlated with FibroTest (τ=0.144, P=0.057), while FIB-4 was correlated (τ=0.256, P=0.001). The same pattern was shown at 12 months post-EOT. Between baseline and the 6-month evaluation, there was a significant decrease in APRI (P<0.001) and FIB-4 (P<0.001) scores, but for the next follow-up period, there was no reduction. In the non-cirrhotic group, APRI and FIB-4 did not correlate with the FibroTest value at any of the evaluation times. There was a significant difference between baseline and the 6-month visit for APRI (P=0.01) and for FIB-4 (P=0.014). The areas under the receiver operating characteristics curve (AUROCs) for the presence of cirrhosis compared with FibroTest for APRI and FIB-4 were 0.682 [95% confidence interval (CI), 0.613-0.752] and 0.693 (95% CI 0.625-0.76). Both APRI and FIB-4 prove to be easy, quick and inexpensive tools for screening HCV cirrhosis, with moderate diagnostic accuracy and FIB-4 can be useful for monitoring patients post-EOT.