Rare host variants in ciliary expressed genes contribute to COVID-19 severity in Bulgarian patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020-April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit ß, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.

Comparative Analysis on Clinical Characteristics Among Patients with Acute Hepatitis A Virus (HAV) and Patients with Acute Hepatitis E Virus (HEV): A Single-Center Retrospective Study from Bulgaria.

Introduction: The acute viral hepatitis was one of the most common conditions in daily clinical practice varying in different parts of the world. The aim of the present study was to perform a comparative analysis on clinical characteristics among patients with acute hepatitis A virus (HAV) infection and patients with acute hepatitis E virus (HEV) infection admitted to the Military Medical Academy (MMA), Sofia, Bulgaria. Methods: A retrospective study was performed at MMA, between 1 January 2016 and 31 December 2021. The etiological diagnosis was confirmed by enzyme-linked immunosorbent assay (ELISA) HAV/HEV IgM serology assays. Results: The current survey included 231 patients with mean age 45.11 ± 16.08 years (95% confidence interval: 43.04-47.19). According to the case definition, inclusion and exclusion criteria, persons were divided into two groups: patients with acute HAV infection (68.4%; 158/231) and patients with acute HEV infection (31.6%; 73/231). Males with HEV had 3.091 times the odds of comorbidity "hypertension" than males with HAV (p = 0.032). There were almost equal odds of increased ALT (odds ratio = 0.999; p = 0.003) in men with HEV and men with HAV. Females with HEV had 5.161 times the odds of comorbidity "hypertension" compared with females with HAV (p = 0.049). We found almost equal odds for elevated ALT in women with HEV and women with HAV (OR = 0.999; p = 0.025). In the non-elderly group (<60-year-old), HEV individuals had 4.544 and 10.560 times the odds of comorbidities "hypertension" and "cardiovascular diseases" compared with HAV patients (p < 0.05). We found almost equal odds for elevated ALT in HEV patients and HAV participants (OR = 0.998; p = 0.002). Conclusion: The results from the current study may support the physicians daily care for patients with acute HAV and acute HEV.

Virus-Specific Stem Cell Memory CD8+ T Cells May Indicate a Long-Term Protection against Evolving SARS-CoV-2.

Immune memory to SARS-CoV-2 is key for establishing herd immunity and limiting the spread of the virus. The duration and qualities of T-cell-mediated protection in the settings of constantly evolving pathogens remain an open question. We conducted a cross-sectional study of SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at several time points over 18 months (30-750 days) post mild/moderate infection with the aim to identify suitable methods and biomarkers for evaluation of long-term T-cell memory in peripheral blood. Included were 107 samples from 95 donors infected during the periods 03/2020-07/2021 and 09/2021-03/2022, coinciding with the prevalence of B.1.1.7 (alpha) and B.1.617.2 (delta) variants in Bulgaria. SARS-CoV-2-specific IFNγ+ T cells were measured in ELISpot in parallel with flow cytometry detection of AIM+ total and stem cell-like memory (TSCM) CD4+ and CD8+ T cells after in vitro stimulation with peptide pools corresponding to the original and delta variants. We show that, unlike IFNγ+ T cells, AIM+ virus-specific CD4+ and CD8+ TSCM are more adequate markers of T cell memory, even beyond 18 months post-infection. In the settings of circulating and evolving viruses, CD8+ TSCM is remarkably stable, back-differentiated into effectors, and delivers immediate protection, regardless of the initial priming strain.

Students' Attitudes toward COVID-19 Vaccination: An Inter-University Study from Bulgaria.

In Bulgaria, vaccination coverage against the SARS-CoV-2 virus is low. The reasons for this fact are many and varied. The aim of the present study was to establish what the attitudes towards the COVID-19 vaccination process are among students from various specialties from several Bulgarian universities. In this research, 600 students participated, divided into two groups: Doctor of Medicine (MD) students (n = 300) and non-MD students, i.e., students of specialties, such as mathematics, engineering, finance and economics, law, human sciences, etc. (n = 300). Each respondent completed a questionnaire which was divided into three parts with closed questions. The mean age of all students was 21.19 ± 1.87 years (95% CI: 20.48−21.90). The female sex dominated among the analyzed participants (sex ratio: female/male = 1/0.85). Nearly 62% (371/600) of individuals declared that they have been COVID-19 vaccinated with at least one dose (p < 0.001). Overall, 33% of the participants sought information on vaccines from video sharing platforms and 36.0% (216/600) from social media platforms. From the conducted multivariable logistic regression the odds of vaccination against COVID-19 were 6.225 times higher in individuals with a positive attitude towards these vaccines than in people with a negative attitude towards them (p < 0.001). We have found that those students who trust the international health organizations had an OR of 2.365 (p = 0.004) to be SARS-CoV-2 vaccinated. We estimated that the odds of vaccination against SARS-CoV-2 among children were 4.794 times higher in parents (students) who had been vaccinated than in non-vaccinated parents (students) (p < 0.001). Our results could support the national public health organizations, the national educational/scientific systems, and the management of Bulgarian universities in making future decisions about the field of COVID-19 control and prevention.