Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [p = 0.00348, area under the receiver operating characteristic curve (AUC ROC = 0.68)]. In particular, presence of HLA-A*01:01 allele was associated with high risk, while HLA-A*02:01 and HLA-A*03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A*01:01 accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort (n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.
The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD inhibition may have a significantly broader effect, in addition to stimulating the endogenous Epo production. The analysis of HIF target genes reveals that some HIF-targets, such as furin, could play a negative role with respect to viral entry. On the other hand, HIF prolyl hydroxylase inhibitors counteract ferroptosis, the process recently implicated in vessel damage during the later stages of COVID-19. Therefore, HIF prolyl hydroxylase inhibitors may serve as a promising treatment of COVID-19 complications, but they are unlikely to aid in the prevention of the initial stages of infection.
Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.
102Всемирная организация здравоохранения (ВОЗ) определяет качество жизни (КЖ) как индивидуаль-ное восприятие человеком своей позиции в жизни в контексте с культурной средой, в которой он про-живает, и системой ценностей, в соответствии с его целями, ожиданиями, стандартами и воззрениями [1]. В работах Testa M, Simonson D (1996) это понятие включает основные группы критериев: физические, психические и социальные [2].При наличии большого количества работ, посвя-щенных изучению психологических особенностей и КЖ больных ишемической болезнью сердца, неко-торые аспекты данной проблемы остаются недоста-точно разработанными. Так, снижение КЖ при ише-Цель. Качество жизни -интегральный показатель эффективности медицин-ской помощи. При неполной реваскуляризации после острого инфаркта мио-карда (ИМ) качество жизни может изменяться соответственно объёму и харак-теру остаточного поражения. Исследование проведено с целью выяснить особенности качества жизни больных в подобной клинической ситуации. Материал и методы. Проведено обследование 100 больных (cредний воз-раст 63±0,9 лет) острым ИМ с подъемом сегмента st с неполной реваскуляри-зацией миокарда, из них 20 было проведено отсроченное оперативное вмеша-тельство (чрескожное коронарное вмешательство или коронарное шунтиро-вание) -группа 1; 54 пациентам дальнейшее оперативное лечение не прово-дилось -группа 2; 26 пациентам не проводилась первичная реваскуляризация -группа 3. Качество жизни оценивали с помощью опрос-ника Medical outcomes study 36 (sF-36). Тестирование проводили через 12 месяцев после перенесенного ИМ. Результаты. Качество жизни у больных группы 1 претерпевает значительные изменения после реваскуляризации миокарда в сторону улучшения как физи-ческого, так и психического компонентов здоровья. Показатели качества жизни в группе 1 через год остаются высокими, приближаясь к "полному" здоровью. У пациентов групп 2 и 3 отмечено ограничение социальных контак-тов, снижение уровня общения в связи с ухудшением физического и эмоцио-нального состояния. Заключение. После отсроченной реваскуляризации в сравнении с её отсут-ствием или с вмешательством только на инфаркт-связанной артерии показа-тели качества жизни после ИМ достоверно выше. Aim. Life quality is an integral parameter of medical care efficacy. in incomplete revascularization after myocardial infarction the quality of life might change in relevance with the severity of residual lesion. the study is done with an aim to reveal the specifics of patients life quality in such clinical situation. Material and methods. the investigation of 100 patients is done (mean age 63±0,9 y. o.) with acute st-elevation myocardial infarction and incomplete revascularization, of those 20 underwent delayed surgery (percutaneous or bypass) -group 1; 54 had no further surgery (group 2); and 26 did not have primary revascularization -group 3. Life quality was assessed with the Medical outcomes sF-36. the test was performed in 12 months after index event.Results. Life quality of group 1 patients changes significantly after revascularization ...
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