Pneumonia and Related Conditions in Critically Ill Patients—Insights from Basic and Experimental Studies

Kashatnikova, Darya A.; Khadzhieva, Maryam B.; Kolobkov, Dmitry; Belopolskaya, Olesya B.; Smelaya, Tamara V.; Gracheva, A. S.; Калинина, Е. В.; Larin, Sergey; Kuzovlev, Аrtem; Salnikova, Lyubov E.

doi:10.3390/ijms23179896

Cited by 3 publications

(5 citation statements)

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“…The diagnosis of pneumonia was made according to provisional clinical guidelines (ВМР_COVID-19_V17. pdf ( minzdrav.gov.ru )), taking into account the results of chest computed tomography with an assessment of the severity of lung damage using a point scale ( Supplementary Table S1 ), as well as clinical and laboratory data described elsewhere ( Kashatnikova et al, 2022 ). The diagnosis of sepsis has been revised according to the 2021 version of the Sepsis Survival Campaign guide ( Evans et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Severe COVID-19 patients included patients with severe/extremely severe course (57 patients), while non-severe COVID-19 patients included patients with mild/moderate course (29 patients) (Supplementary Table S1). The diagnosis of pneumonia was made according to provisional clinical guidelines ), taking into account the results of chest computed tomography with an assessment of the severity of lung damage using a point scale (Supplementary Table S1), as well as clinical and laboratory data described elsewhere (Kashatnikova et al, 2022). The diagnosis of sepsis has been revised according to the 2021 version of the Sepsis Survival Campaign guide (Evans et al, 2021).…”

Section: Patients and Clinical Datamentioning

confidence: 99%

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COVID-19 severity: does the genetic landscape of rare variants matter?

et al. 2023

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Rare variants affecting host defense against pathogens may be involved in COVID-19 severity, but most rare variants are not expected to have a major impact on the course of COVID-19. We hypothesized that the accumulation of weak effects of many rare functional variants throughout the exome may contribute to the overall risk in patients with severe disease. This assumption is consistent with the omnigenic model of the relationship between genetic and phenotypic variation in complex traits, according to which association signals tend to spread across most of the genome through gene regulatory networks from genes outside the major pathways to disease-related genes. We performed whole-exome sequencing and compared the burden of rare variants in 57 patients with severe and 29 patients with mild/moderate COVID-19. At the whole-exome level, we observed an excess of rare, predominantly high-impact (HI) variants in the group with severe COVID-19. Restriction to genes intolerant to HI or damaging missense variants increased enrichment for these classes of variants. Among various sets of genes, an increased signal of rare HI variants was demonstrated predominantly for primary immunodeficiency genes and the entire set of genes associated with immune diseases, as well as for genes associated with respiratory diseases. We advocate taking the ideas of the omnigenic model into account in COVID-19 studies.

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Section: Methodsmentioning

confidence: 99%

Section: Patients and Clinical Datamentioning

confidence: 99%

COVID-19 severity: does the genetic landscape of rare variants matter?

et al. 2023

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“…Given the association demonstrated in the literature between TREC levels and the development of critical conditions and adverse outcomes in patients with COVID-19 and non-COVID-19 pneumonia [ 23 , 24 , 25 , 26 , 27 ], we believe that the results of ROC analysis support the accuracy of phenotype determination in severe and non-severe COVID-19.…”

Section: Resultsmentioning

confidence: 70%

“…The TREC/KREC levels were assayed in whole blood samples as described previously [ 24 , 27 ]. In brief, DNA was isolated from 200 μL of venous blood via isopropanol precipitation.…”

Section: Methodsmentioning

confidence: 99%

“…The interest in evaluating TREC and KREC levels in severe COVID-19 is bidirectional. On the one hand, given the demonstrated association between TREC and, to a lesser extent, KREC levels and the development of critical conditions and adverse outcomes in patients with COVID-19 [ 23 , 24 , 25 , 26 ] and non-COVID-19 pneumonia [ 27 ], TREC/KREC measurements may be useful in order to confirm the classification of COVID-19 severity. On the other hand, given the importance of selecting immunologic tests with high prognostic value, the additional evaluation of TREC/KREC levels in severe COVID-19 may contribute to the selection and subsequent clinical implementation of prognostic tools for patients with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Rare Variants in Primary Immunodeficiency Genes and Their Functional Partners in Severe COVID-19

Khadzhieva,

Kolobkov,

Kashatnikova

et al. 2023

Biomolecules

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The development of severe COVID-19, which is a complex multisystem disease, is thought to be associated with many genes whose action is modulated by numerous environmental and genetic factors. In this study, we focused on the ideas of the omnigenic model of heritability of complex traits, which assumes that a small number of core genes and a large pool of peripheral genes expressed in disease-relevant tissues contribute to the genetics of complex traits through interconnected networks. We hypothesized that primary immunodeficiency disease (PID) genes may be considered as core genes in severe COVID-19, and their functional partners (FPs) from protein–protein interaction networks may be considered as peripheral near-core genes. We used whole-exome sequencing data from patients aged ≤ 45 years with severe (n = 9) and non-severe COVID-19 (n = 11), and assessed the cumulative contribution of rare high-impact variants to disease severity. In patients with severe COVID-19, an excess of rare high-impact variants was observed at the whole-exome level, but maximal association signals were detected for PID + FP gene subsets among the genes intolerant to LoF variants, haploinsufficient and essential. Our exploratory study may serve as a model for new directions in the research of host genetics in severe COVID-19.

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