TY - JOUR

T1 - Линии короновируса SARS-CoV-2 российского происхождения

T2 - генетическая характеристика и корреляции с клиническими параметрами, тяжестью коронавирусной инфекции

AU - Glotov, Oleg S.

AU - Chernov, Alexander N.

AU - Korobeynikov, Anton I.

AU - Kalinin, Roman S.

AU - Tsai, Viktoria V.

AU - Anisenkova, Anna Yu

AU - Urazov, Stanislav P.

AU - Lapidus, Alla L.

AU - Mosenko, Sergei V.

AU - Shcherbak, Sergei G.

N1 - Funding Information: the study was financed from the budget of the St. Petersburg State Budgetary Healthcare Institution “City Hospital No. 40 of the Kurortny Administrative District” and by St. Petersburg State University (grants ID PURE: 75253103 and ID PURE: 73023672). Publisher Copyright: © 2021 Tomsk State University. All Rights Reserved.

PY - 2021

Y1 - 2021

N2 - The identification of new SARS-CoV-2 and human protein and gene targets, which may be markers of the severity and outcome of the disease, are extremely important during the COVID-19 pandemic. The goal of this study was to carry out genetic analysis of SARS-CoV-2 RNA samples to elucidate correlations of genetic parameters (SNPs) with clinical data and severity of COVID-19 infection. Material and Methods. The study included viral RNA samples isolated from 56 patients with COVID-19 infection who received treatment at the City Hospital No. 40 of St. Petersburg from 04/18/2020 to 04/18/2021. Patients underwent physical examination with the assessments of hemodynamic and respiratory parameters, clinical risk according to National Early Warning Score (NEWS), computed tomography (CT) of the chest, and laboratory studies including clinical blood analysis, assessment of ferritin, C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, creatinine, and glucose levels. All patients tested positive for SARS-CoV-2 RNA by polymerase chain reaction (PCR). Single nucleotide polymorphisms (SNPs) in viral RNA were identified through the creation of cDNA libraries by targeted sequencing (MiSeq Illumina). Bioinformatic analysis of viral samples was performed using the viralrecon v2 pipeline with the further annotation via Pangolin and Nextlade. Sampled genomes were visualized using the Integrative Genomics Viewer (IGV) software. Statistical data processing (descriptive statistics and graphical analysis of data relationships from different tables) was performed using a GraphPad device on the Prism 8.01 platform. Results. A comparative analysis of SNP frequencies in the virus genome in samples from deceased and discharged patients was carried out. The SNPs associated with risk of death (OR > 1), neutral SNPs (OR = 1), and protective SNPs (OR < 1) were identified. Patient samples were infected with 14 lines of SARS-CoV-2, five of which (B.1.1.129, B.1.1.407, B.1.1.373, B.1.1.397, and B.1.1.152) were of Russian origin. The SNPs in the samples infected with the strains of non-Russian origin were associated with an increased risk of mortality (OR = 2.267, 95% confidence interval 0.1594-8.653) compared to the SNPs in the samples obtained from the group of patients infected with the strains of Russian origin. Positive correlations were identified between the average SNP number, nonsynonymous SNPs, and S-protein SNPs with the degree of respiratory failure, total NEWS score, CT-based form of disease, duration of treatment with mechanical ventilation, disease outcome, levels of LDH, glucose, D-dimer, and ferritin, and RNA amount in the PCR test. S-protein SNPs negatively correlated with the leukocyte and neutrophil counts.

AB - The identification of new SARS-CoV-2 and human protein and gene targets, which may be markers of the severity and outcome of the disease, are extremely important during the COVID-19 pandemic. The goal of this study was to carry out genetic analysis of SARS-CoV-2 RNA samples to elucidate correlations of genetic parameters (SNPs) with clinical data and severity of COVID-19 infection. Material and Methods. The study included viral RNA samples isolated from 56 patients with COVID-19 infection who received treatment at the City Hospital No. 40 of St. Petersburg from 04/18/2020 to 04/18/2021. Patients underwent physical examination with the assessments of hemodynamic and respiratory parameters, clinical risk according to National Early Warning Score (NEWS), computed tomography (CT) of the chest, and laboratory studies including clinical blood analysis, assessment of ferritin, C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, creatinine, and glucose levels. All patients tested positive for SARS-CoV-2 RNA by polymerase chain reaction (PCR). Single nucleotide polymorphisms (SNPs) in viral RNA were identified through the creation of cDNA libraries by targeted sequencing (MiSeq Illumina). Bioinformatic analysis of viral samples was performed using the viralrecon v2 pipeline with the further annotation via Pangolin and Nextlade. Sampled genomes were visualized using the Integrative Genomics Viewer (IGV) software. Statistical data processing (descriptive statistics and graphical analysis of data relationships from different tables) was performed using a GraphPad device on the Prism 8.01 platform. Results. A comparative analysis of SNP frequencies in the virus genome in samples from deceased and discharged patients was carried out. The SNPs associated with risk of death (OR > 1), neutral SNPs (OR = 1), and protective SNPs (OR < 1) were identified. Patient samples were infected with 14 lines of SARS-CoV-2, five of which (B.1.1.129, B.1.1.407, B.1.1.373, B.1.1.397, and B.1.1.152) were of Russian origin. The SNPs in the samples infected with the strains of non-Russian origin were associated with an increased risk of mortality (OR = 2.267, 95% confidence interval 0.1594-8.653) compared to the SNPs in the samples obtained from the group of patients infected with the strains of Russian origin. Positive correlations were identified between the average SNP number, nonsynonymous SNPs, and S-protein SNPs with the degree of respiratory failure, total NEWS score, CT-based form of disease, duration of treatment with mechanical ventilation, disease outcome, levels of LDH, glucose, D-dimer, and ferritin, and RNA amount in the PCR test. S-protein SNPs negatively correlated with the leukocyte and neutrophil counts.

KW - biochemical markers

KW - clinical symptoms

KW - correlations

KW - COVID-19 infection

KW - genes

KW - SARS-CoV-2

KW - severity

KW - SNP

UR - http://www.scopus.com/inward/record.url?scp=85126139709&partnerID=8YFLogxK

U2 - 10.29001/2073-8552-2021-36-4-132-143

DO - 10.29001/2073-8552-2021-36-4-132-143

M3 - статья

AN - SCOPUS:85126139709

VL - 36

SP - 132

EP - 143

JO - Siberian Journal of Clinical and Experimental Medicine

JF - Siberian Journal of Clinical and Experimental Medicine

SN - 2713-2927

IS - 4

ER -