Buchynskyi M. The impact of targeted antiviral therapy on clinical, laboratory, and immune parameters in patients with COVID-19 and comorbid metabolic associated fatty liver disease

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0826U001264

Thesis Registration Form

0826U001264.pdf

Applicant for

Specialization

  • 222 - Медицина

Specialized Academic Board

PhD 13111

Ternopil National Medical University named after I. Gorbachevsky of the Ministry of Health of Ukraine

Essay

The dissertation is devoted to a comprehensive study of the impact of targeted antiviral therapy on the clinical, laboratory, immune, and molecular-genetic parameters in patients with COVID-19 comorbid with metabolic associated fatty liver disease (MAFLD). It has been established that the presence of MAFLD in patients with COVID-19 is not an independent risk factor for a severe disease course; rather, its impact is mediated by other concomitant metabolic factors, which refutes previously existing hypotheses. In a cohort of patients with MAFLD, the efficacy of targeted antiviral therapy with nirmatrelvir/ritonavir was evaluated, confirming its high clinical effectiveness regardless of the presence of this comorbidity, and demonstrating its benefits in reducing hospitalization time and improving clinical outcomes. The impact of single nucleotide polymorphisms (SNPs) in the IFNAR2, ACE2, OAS1, and OAS3 genes on clinical and laboratory parameters and their dynamic changes in patients with COVID-19 and MAFLD was investigated. It was found that certain alleles are associated with a more or less favorable disease course and treatment response, opening new perspectives for personalized medicine. For the first time in the Ukrainian population, the expression of AHR, FFAR2, FXR, and TGR5 genes in COVID-19 patients was studied, allowing the determination of their role in disease pathogenesis and the identification of new interrelationships. Notably, it was shown that reduced AHR expression in MAFLD patients is associated with elevated coagulation parameters, indicating its potential role in the development of thrombotic complications. It was discovered that reduced expression of FXR and TGR5 correlates with disease severity, as well as with indicators of systemic inflammation and metabolism.

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Research papers

1. Buchynskyi, M.; Kamyshna, I.; Lyubomirskaya, K.; Moshynets, O.; Kobyliak, N.; Oksenych, V.; Kamyshnyi, A. Efficacy of Interferon Alpha for the Treatment of Hospitalized Patients with COVID-19: A Meta-Analysis. Front. Immunol. 2023, 14, 1069894, doi:10.3389/FIMMU.2023.1069894.

2. Kamyshnyi, A.; Koval, H.; Kobevko, O.; Buchynskyi, M.; Oksenych, V.; Kainov, D.; Lyubomirskaya, K.; Kamyshna, I.; Potters, G.; Moshynets, O. Therapeutic Effectiveness of Interferon-Α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience. Int. J. Mol. Sci. 2023, 24, 6887, doi:10.3390/ijms24086887.

3. Buchynskyi, M.; Oksenych, V.; Kamyshna, I.; Kamyshnyi, O. Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study. Viruses, 2024, 16,1, 112, doi:10.3390/v16010112.

4. Buchynskyi, M.; Oksenych, V.; Kamyshna, I.; Vorobets, I.; Halabitska, I.; Kamyshnyi, O. Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes. Viruses, 2024, 16,6, 985, doi:10.3390/v16060985.

5. Buchynskyi, M.; Oksenych, V.; Kamyshna, I.; Budarna, O.; Halabitska, I.; Petakh, P.; Kamyshnyi, O. Genomic Insight into COVID-19 Severity in MAFLD Patients: A Single-Center Prospective Cohort Study. Front. Genet. 2024, 15, 1460318, doi:10.3389/fgene.2024.1460318.

6. Buchynskyi, M.; Kamyshna, I.; Halabitska, I.; Petakh, P.; Oksenych, V.; Kamyshnyi, O. Genetic Predictors of Paxlovid Treatment Response: The Role of IFNAR2, OAS1, OAS3, and ACE2 in COVID-19 Clinical Course. J. Pers. Med. 2025, 15,4, 156, doi:10.3390/jpm15040156.

7. Buchynskyi, M.; Kamyshna, I.; Oksenych, V.; Zavidniuk, N.; Kamyshnyi, A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses, 2023, 15,5, 1072, doi:10.3390/v15051072.

8. Buchynskyi, M.; Oksenych, V.; Kamyshna, I.; Vari, S.G.; Kamyshnyi, A. Genetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis. Viruses, 2023, 15,8, 1724, doi:10.3390/V15081724.

9. Buchynskyi, M.; Kamyshna, I.; Halabitska, I.; Petakh, P.; Kunduzova, O.; Oksenych, V.; Kamyshnyi, O. Unlocking the Gut-Liver Axis: Microbial Contributions to the Pathogenesis of Metabolic-Associated Fatty Liver Disease. Front. Microbiol. 2025, 16, 1577724, doi:10.3389/fmicb.2025.1577724.

10. Buchynskyi, M. Impact of Paxlovid Treatment on Clinical Outcomes in COVID-19 Patients with Metabolic-Associated Fatty Liver Disease. In Proceedings of 19th RECOOP Bridges in Life Sciences Conference , Bratislava, 11-12 April 2024; Bratislava, 2024; p. 76.

11. Бучинський, М.В. Роль експресії генів AHR, FFAR2, FXR і TGR5 у взаємодії COVID-19 та метаболічно асоційованої жирової хвороби печінки. У Матеріалах LXVІI науково-практичної конференції «Здобутки клінічної та експериментальної медицини», Тернопіль, 13-14 червня 2024; Тернопіль, 2024; с. 5-7.

12. Бучинський, М.В. Вплив генетичних поліморфізмів IFNAR2, OAS1, OAS3 і ACE2 на клініко-лабораторні показники у пацієнтів з COVID-19, лікованих PAXLOVID. У Матеріалах ХІV науково-практичної конференції «Актуальні питання патології за умов дії надзвичайних факторів на організм», Тернопіль, 23-25 жовтня 2024; Тернопіль, 2024; с. 12.

13. Buchynskyi, M. The role of host genetics in modulating COVID-19 response to Paxlovid treatment. In Proceedings of the 20th RECOOP Bridges in Life Sciences Conference, Prague, 2-3 April 2025; Prague, 2025; p. 26.

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Дисертація Бучинського М-В-.pdf

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