The Influence of HLA Polymorphisms on the Severity of COVID-19 in the Romanian Population.

In this study, we aimed to investigate whether specific HLA alleles found in patients from Romania and the Republic of Moldova were associated with the severity of COVID-19 infection and its associated mortality. We analyzed the HLA alleles at the -A, -B, -C, -DRB1, and -DQB1 loci in a cohort of 130 individuals with severe and extremely severe forms of COVID-19, including 44 individuals who died. We compared these findings to a control group consisting of individuals who had either not been diagnosed with COVID-19 or had experienced mild forms of the disease. Using multivariate logistic regression models, we discovered that the B*27 and B*50 alleles were associated with an increased susceptibility to developing a severe form of COVID-19. The A*33 and C*15 alleles showed potential for offering protection against the disease. Furthermore, we identified two protective alleles (A*03 and DQB1*02) against the development of extremely severe forms of COVID-19. By utilizing score statistics, we established a statistically significant association between haplotypes and disease severity (p = 0.021). In summary, this study provides evidence that HLA genotype plays a role in influencing the clinical outcome of COVID-19 infection.

HLA-DR and HLA-DQ Polymorphism Correlation with Sexually Transmitted Infection Caused by Chlamydia trachomatis.

Background and Objectives: Chlamydia trachomatis (C. trachomatis) represents one of the most prevalent bacterial sexually transmitted diseases. This study aims to explore the relationship between HLA alleles/genotypes/haplotypes and C. trachomatis infection to better understand high-risk individuals and potential complications. Materials and Methods: This prospective study recruited participants from Transylvania, Romania. Patients with positive NAAT tests for C. trachomatis from cervical/urethral secretion or urine were compared with controls regarding HLA-DR and -DQ alleles. DNA extraction for HLA typing was performed using venous blood samples. Results: Our analysis revealed that the presence of the DRB1*13 allele significantly heightened the likelihood of C. trachomatis infection (p = 0.017). Additionally, we observed that individuals carrying the DRB1*01/DRB1*13 and DQB1*03/DQB1*06 genotype had increased odds of C. trachomatis infection. Upon adjustment, the association between the DRB1*01/DRB1*13 genotype and C. trachomatis remained statistically significant. Conclusions: Our findings underscore the importance of specific HLA alleles and genotypes in influencing susceptibility to C. trachomatis infection. These results highlight the intricate relationship between host genetics and disease susceptibility, offering valuable insights for targeted prevention efforts and personalized healthcare strategies.

Flurona: The First Autopsied Case.

COVID-19-associated coinfections increase the patient's risk of developing a severe form of the disease and, consequently, the risk of death. The term "flurona" was proposed to describe the coinfection of the influenza virus and SARS-CoV-2. This report is about a case of a 7-month-old female infant who died due to flurona coinfection. A histopathological exam showed activation of microglia (becoming CD45 positive), bronchial inflammation, diffuse alveolar damage in proliferative phase with vasculitis, a peribronchial infiltrate that was predominantly CD20-positive, and a vascular wall infiltrate that was predominantly CD3-positive. The aggressiveness of the two respiratory viruses added up and they caused extensive lung inflammation, which led to respiratory failure, multiple organ failure, and death. Tissues injuries caused by both the influenza virus and SARS-CoV-2 could be observed, without the ability to certify the dominance of the aggression of one of the two viruses.

Asymptomatic Esophageal Necrosis in a Patient with Recent COVID-19: The First Case Diagnosed through Autopsy.

Acute esophageal necrosis is a rare condition, characterized by a distinctive endoscopic/necropsic image-circumferential black area of the esophagus. This paper presents a case of a 78-year-old patient with recent history of a severe form of COVID-19 (2 months previously), with multiple comorbidities, which presents sudden death in hospital. Anatomic-pathological autopsy showed extensive esophageal necrosis, pulmonary thromboses, and coronarian and aortic atherosclerosis. The histopathological examination revealed necrosis of the esophageal mucosa and phlegmonous inflammation extended to the mediastinum, chronic pneumonia with pulmonary fibrosis, viral myocarditis, papillary muscle necrosis, and pericoronary neuritis. Thromboses and necroses were identified also in the liver, pancreas, and adrenal glands. Post-COVID-19 thromboses can manifest late, affecting various vascular territories, including esophageal ones. Their clinical picture may be diminished or absent in elderly and/or diabetic patients.

Fatal Form of COVID-19 in a Young Male Bodybuilder Anabolic Steroid Using: The First Autopsied Case.

We report the case of a 34-year-old male patient, a bodybuilding trainer and user of anabolic androgenic steroids (AASs) for 16 years. He was found in cardio-respiratory arrest in his home. By performing a medico-legal autopsy, a severe form of COVID-19, aortic atherosclerotic plaques, and an old myocardial infarction was found. The SARS-CoV-2 RT-PCR test on necroptic lung fragments was positive, with a B.1.258 genetic line. The histopathological examinations showed microthrombi with endothelitis in the cerebral tissue, massive pulmonary edema, diffuse alveolar damage grade 1, pulmonary thromboembolism, hepatic peliosis, and severe nesidioblastosis. The immunohistochemical examinations showed SARS-CoV-2 positive in the myocardium, lung, kidneys, and pancreas. ACE-2 receptor was positive in the same organs, but also in the spleen and liver. HLA alleles A*03, A*25, B*18, B*35, C*04, C*12, DRB1*04, DRB1*15, DQB1*03, DQB1*06 were also identified. In conclusion, death was due to a genetic predisposition, a long-term abuse of AASs that favored the development of a pluriorganic pathological tissue terrain, and recent consumption of AASs, which influenced the immune system at the time of infection.

Association between HLA class II alleles and hepatitis B virus infection in Transylvania, Romania.

Infection with hepatitis B virus (HBV) is a major problem worldwide. The major histocompatibility complex plays an essential role in host immunity and can help eliminate the HBV of infected hepatocytes. Our study aimed to determine the role of certain human leukocyte antigen (HLA) class II molecules (i.e. HLA-DRB1 and HLA-DQB1) in the persistence or removal of HBV. Sixty patients confirmed to be HBV-positive via real-time polymerase chain reaction (PCR), i.e. people with chronic active hepatitis, were included in the study along with a control group of 100 healthy individuals without evidence of HBV infection. The DNA was subsequently used to determine HLA-DRB1 and HLA-DQB1 low-resolution typing genetic profile via PCR amplification. The univariate analysis performed revealed significant association of the HLA-DRB1*03 and HLA-DQB1*05 alleles to the infected persons (study group), while HLA-DRB1*01 was shown to be protective against HBV infection. To our knowledge, this is the first Romanian study associating HLA with HBV, and it can provide valuable insight concerning the relationship between genetic factors and immune response in the sampled population.

COVID-19-Associated Rhino-Orbital Mucormycosis: Histological and Electron Microscopy Characteristics.

COVID-19-associated rhino-orbital mucormycosis has become a new clinical entity. This study's aim was to evaluate the histopathological and ultramicroscopic morphological aspects of this fungal infection. This was an observational retrospective study on eight patients from three tertiary centers in Romania. The tissue samples collected during functional endoscopic sinus surgery were studied through histopathological examination, scanning electron microscopy, and transmission electron microscopy. In the histopathological examination, the morphological aspects characteristic of mucormycosis in all cases were identified: wide aseptate hyphae with right-angle ramifications, which invade blood vessels. One case presented perineural invasion into the perineural lymphatics. And in another case, mucormycosis-aspergillosis fungal coinfection was identified. Through scanning electron microscopy, long hyphae on the surface of the mucosa surrounded by cells belonging to the local immune system were identified in all samples, and bacterial biofilms were identified in half of the samples. Through transmission electron microscopy, aseptate hyphae and bacterial elements were identified in the majority of the samples. Rhino-orbital-cerebral mucormycosis associated with COVID-19 produces nasal sinus dysbiosis, which favors the appearance of bacterial biofilms. The way in which the infection develops depends on the interaction of the fungi with cells of the immune system.

Chlamydia trachomatis and the HLA involvement in the development of infection and disease: a narrative review.

Introduction: CT (Chlamydia trachomatis) is among the most common pathogens leading to sexually transmitted diseases. Considering the uncertain mechanism by which HLA polymorphisms influence the CT infection, reinfection, comorbidities or evolution and because there is no consensus regarding the alleles involved in the pathogenesis of the infection, we considered necessary to perform a review to summarize the current knowledge of HLA related to CT. Methods: Pubmed was researched using key terms. Out of the 198 results found, we analyzed articles of all types which describe how the MHC, through HLA alleles, participates in the different stages of CT penetration in the body, including studies about cells or other molecules involved in the process. Results: Almost 40% of the variation in the clinical course of CT infection depends on host genetic factors. There are haplotypes that influence the infection susceptibility/resistance, haplotypes that are involved in the recurrence of the infection, haplotypes that are related to tubal infertility, pelvic inflammatory disease development or trachoma. Antibody to Chsp60 (influenced by MHC genes) has been observed to correlate with late tissue-damaging sequelae. Toll-like receptors were found to increase the susceptibility to CT. The association of HLA-B27 creates susceptibility of reactive arthritis in the organisms infected by CT, but does not influence the carriage of CT. Conclusion: We identified HLA haplotypes belonging both to MHC class l and ll, which influence different stages of CT infection. Genetic risk factors still need research, especially on Caucasians. Studies are moving towards designing a safe and effective vaccine.

Impact of the COVID-19 Pandemic on the Suicidal Behavior in Romania.

Suicide rates reflect the mental health status in certain countries or regions. As the COVID-19 infection developed as a pandemic and governments imposed certain measures to stop the spread of the virus, mental health was affected worldwide. Romania was no exception as the government issued a complete lockdown with restriction regarding travels, social gatherings, transition to working from home and others. The increase in the rate of unemployment, the difficulties in accessing the health services and the social distancing generated by the restrictions had a major impact on lifestyle with a potential surge of psychiatric disorders, with or without history of illness. In this study, we analyzed the changes in regard to the number of suicides and suicide attempts as well as the methods employed and the underlying psychiatric pathology in Cluj County, Romania, throughout the first year of the pandemic. The results had not revealed changes in the overall suicide rate, but in the case of mild cognitive disorders and dementia the suicide figures increased, while a decrease was observed in the number of suicides related to substance use disorders. The long-term effects of the pandemic remain unknown, but there is a clear impact on mental health and measures should be taken in order to prevent suicides.

Risk factors for suicidal behavior: A Romanian mixed methods study.

OBJECTIVES: This study had two purposes: to explore the main socio-demographic and medical characteristics of the psychiatric patients with a history of suicidal behavior, and to identify the main risk factors underlying the suicidal ideation and acts among psychiatric patients, in the light of two recent theories of suicidal behavior. METHODS: The study is based on a mixed methodological design. During 2019 to 2021, 65 hospitalized psychiatric patients, who committed at least one non-lethal suicide attempt, were investigated using a questionnaire a scales for data collection. Medical records were used to gather data about certain socio-demographic characteristics and the health status of the respondents. Patients also participated in a narrative interview aimed at disclosing their subjective experiences about their past suicidal behavior. RESULTS: The typical psychiatric patient with a history of suicidal behavior, as highlighted by the quantitative analysis, portraits a young old male from an urban environment, childless, educated, having experienced employment problems, being involved in religious activities. The clinical picture of the patient with suicidal antecedents included a moderate or severe level of depression, the presence of socio-emotional loneliness, the manifestation of frequent and long episodes of suicidal ideation, and the intention of committing suicide in order to stop the pain, whose acts resulted in minor injuries. Findings from the qualitative data revealed four major risk factors for the non-lethal suicidal attempts: family disruptions and social problems; economic burdens; a mixture of psychiatric pathologies; and, to a lesser extent, somatic pathologies. CONCLUSION: This study is the first to explore the triggers of suicide acts conducted in a clinical environment in the Balkan region. Implications of the pandemic are also discussed. The findings are useful for designing prevention strategies based on individual psychotherapy and therapeutic or support groups, addressing the main risk factors behind the suicidal ideation and gestures.

Histopathological Lung Findings in COVID-19 B.1.617.2 SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant. METHODS: The study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody). RESULTS: Virology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells. CONCLUSIONS: The histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.

The Influence of HLA Alleles on the Affective Distress Profile.

(1) Background: Affective distress can be triggered by aggressive stimuli with an unfavorable role for the individual. Some of the factors that lead to the development and evolution of a mental disorder can be genetic. The aim of this study is to determine some correlations between the human leukocyte antigen (HLA) genes and the affective distress profile (PDA). (2) Methods: A psychological assessment and testing tool for anxiety was applied to 115 people. The low-resolution HLA alleles of class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) were identified by the PCR technique after DNA extraction from the blood. Depending on the PDA, the subjects were divided into two groups: a group with a low PDA and another one with a medium and high PDA. The IBM SPSS software was used to compare the frequency of HLA alleles between the two groups. (3) Results: The univariate analysis revealed a significant association of the HLA-A locus (A*01, A*30), HLA-B (B*08), and HLA-DRB1 (DRB1*11) with the low PDA group and of the HLA-A locus (A*32), HLA-B (B*52), and HLA-C (C*12) with the medium and high PDA group. (4) Conclusions: The present study highlighted potential associations between HLA alleles and anxiety disorders.

Determinants of Suicide Ideation in the Romanian Population.

BACKGROUND: Suicide ideation and behaviors are directly linked to the risk of death by suicide. In Romania, as well as worldwide, increased suicide rates were observed in the recent past, more so in the context of the COVID-19 pandemic. The purpose of this study was to investigate the influence of psychosocial factors, quality of life (QOL), and loneliness dimensions and adverse life antecedents on suicide ideation (SI) and prolonged sadness (PS). METHODS: This cross-sectional quantitative research study used a CATI data gathering method to investigate 1102 randomly selected individuals over 18 years of age regarding various determinants of SI and PS. Data were collected in June 2021. Descriptive, inferential, and multivariate statistics were used for data analysis. RESULTS: SI was negatively correlated with all the assessed psychosocial factors, more significantly with family relationships, wealth, health, social relationships, and affective life. Stronger correlations were observed when investigating the state of prolonged sadness, sex, and affective lives along with health and income, which were more influential. SI was negatively correlated with QOL and positively correlated with adverse life events and total loneliness scores. Lesser educated youngsters with reduced overall happiness and a history of depression, self-harm, and trauma were at greater risk of developing SI. CONCLUSIONS: This is the first national study exploring the suicide ideation and prolonged sadness in relation to psychosocial factors, quality of life, and adverse life events. These results have important implications for suicide prevention programs, which should be designed in accordance with similar studies.

Antibacterial Activity of Propolis Extracts from the Central Region of Romania against Neisseria gonorrhoeae.

(1) Background: Sexually transmitted infections (STIs) are among the most common infections worldwide, many of these being caused by Neisseria gonorrhoeae (NG). Increased antimicrobial NG resistance has been reported in recent decades, highlighting the need for new sources of natural compounds with valuable antimicrobial activity. This study aims to determine the effect of propolis extracts on NG strains, including antibiotic-resistant strains. (2) Methods: First void urine samples from presumed positive STI subjects were harvested. DNA was extracted, purified, and amplified via PCR for the simultaneous detection of 6 STIs. The presence of the dcmH, gyrA, and parC genes was checked in the DNA samples from NG-positive patients. The antimicrobial activity of 5 aqueous propolis extracts from central Romania was investigated in vitro against some isolated NG strains. ANOVA tests were employed to assess differences and interactions between the inhibition zone for NG strains and propolis extracts. (3) Results: 7.07% of the patients presented NG infections, some strains being resistant or intermediate-resistant to ciprofloxacin. All propolis samples exhibited an antibacterial effect, including on resistant strains. (4) Conclusions: Statistical analysis demonstrated that the diameter of the inhibition zone was influenced both by the NG strain type and the source of the propolis extracts.

Respiratory Nasal Mucosa in Chronic Rhinosinusitis with Nasal Polyps versus COVID-19: Histopathology, Electron Microscopy Analysis and Assessing of Tissue Interleukin-33.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most studied rhinological disorders. Modifications of the respiratory nasal mucosa in COVID-19 patients are so far unknown. This paper presents a comparative morphological characterization of the respiratory nasal mucosa in CRSwNP versus COVID-19 and tissue interleukin (IL)-33 concentration. (2) Methods: We analyzed CRSwNP and COVID-19 samples through histopathology, scanning and transmission electron microscopy and performed proteomic determination of IL-33. (3) Results: Histopathologically, stromal edema (p < 0.0001) and basal membrane thickening (p = 0.0768) were found more frequently in CRSwNP than in COVID-19. Inflammatory infiltrate was mainly eosinophil-dominant in CRSwNP and lymphocyte-dominant in COVID-19 (p = 0.3666). A viral cytopathic effect was identified in COVID-19. Scanning electron microscopy detected biofilms only in CRSwNP, while most COVID-19 samples showed microbial aggregates (p = 0.0148) and immune cells (p = 0.1452). Transmission electron microscopy of CRSwNP samples identified biofilms, mucous cell hyperplasia (p = 0.0011), eosinophils, fibrocytes, mastocytes, and collagen fibers. Extracellular suggestive structures for SARS-CoV-2 and multiple Golgi apparatus in epithelial cells were detected in COVID-19 samples. The tissue IL-33 concentration in CRSwNP (210.0 pg/7 µg total protein) was higher than in COVID-19 (52.77 pg/7 µg total protein) (p < 0.0001), also suggesting a different inflammatory pattern. (4) Conclusions: The inflammatory pattern is different in each of these disorders. Results suggested the presence of nasal dysbiosis in both conditions, which could be a determining factor in CRSwNP and a secondary factor in COVID-19.

Assessment of STI screening in Romania using a multiplex PCR technique.

INTRODUCTION: Most sexually transmitted infections (STIs) are curable, but inappropriate treatment can lead to serious complications. The importance of setting up STI screening programs has been highlighted in various studies, the absence of such national programs accounting for the lack of STI statistics in Romania. The purpose of our study was to evaluate multiplex PCR as a screening method for the most common 6 STIs and establish their frequency in a group of symptomatic and asymptomatic patients. We aimed to highlight STI associations and correlations between STI pathogens and symptomatology, demographic status, antecedents or sexual partners. METHODOLOGY: A total of 249 patients, both symptomatic and asymptomatic, were included in this study. Chlamydia trachomatis (CT), Neisseia gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma urealyticum (UU), Mycoplasma hominis (MH) and Mycoplasma genitalium (MG) were all identified in urine samples via multiplex Polymerase Chain Reaction (PCR). The SPSS IBM program was employed for statistical analysis. RESULTS: 32.12% of the patients were found positive, some presenting multiple infections. The results are representative for the Romanian male population. 107 STI pathogens were identified, most frequent being CT, UU and NG. Several statistical correlations between patient characteristics and the presence of STIs have been demonstrated. CONCLUSIONS: The results suggest that multiplex PCR meets all the prerequisites for a screening method, allowing the use of multiple specimens and enabling simultaneous detection of multiple pathogens in a short period of time. STI identification via multiplex PCR proved to be an effective method for quantifying their frequency in Romania.