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4 Publications visible to you, out of a total of 4
Molecular Analysis of SARS-CoV-2 Lineages in Armenia

Abstract (Expand)

The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and … Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity. Phylodynamic and transmission analysis allowed to attribute specific clades as well as infer their importation routes. Thus, the first two waves of positive case increase were caused by the 20B clade, the third peak caused by the 20I (Alpha), while the last two peaks were caused by the 21J (Delta) and 21K (Omicron) variants. The functional analyses of mutations in sequences largely affected epitopes associated with protective HLA loci and did not cause the loss of the signal in PCR tests targeting ORF1ab and N genes as confirmed by RT-PCR. We also compared the performance of nanopore and Illumina short-read sequencing and showed the utility of nanopore sequencing as an efficient and affordable alternative for large-scale molecular epidemiology research. Thus, our paper describes new data on the genomic diversity of SARS-CoV-2 variants in Armenia in the global context of the virus molecular genomic surveillance.

Authors: Diana Avetyan, Siras Hakobyan, Maria Nikoghosyan, Lilit Ghukasyan, Gisane Khachatryan, Tamara Sirunyan, Nelli Muradyan, Roksana Zakharyan, Andranik Chavushyan, Varduhi Hayrapetyan, Anahit Hovhannisyan, Shah A. Mohamed Bakhash, Keith R. Jerome, Pavitra Roychoudhury, Alexander L. Greninger, Lyudmila Niazyan, Mher Davidyants, Gayane Melik-Andreasyan, Shushan Sargsyan, Lilit Nersisyan, Arsen Arakelyan

Date Published: 17th May 2022

Publication Type: Journal

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

Abstract (Expand)

The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte … antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%).

Authors: Anahit Hovhannisyan, Vergine Madelian, Sevak Avagyan, Mihran Nazaretyan, Armine Hyussyan, Alina Sirunyan, Rubina Arakelyan, Zorayr Manukyan, Levon Yepiskoposyan, Karine R. Mayilyan, Frieda Jordan

Date Published: 3rd Feb 2022

Publication Type: Journal

The Evolving Faces of the SARS-CoV-2 Genome

Abstract (Expand)

Surveillance of the evolving SARS-CoV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and … space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for ‘bioinformatics surveillance’ of the pandemic, with strong odds regarding visualization, intuitive perception and ‘personalization’ of the mutational patterns of the virus genomes.

Authors: Maria Schmidt, Mamoona Arshad, Stephan H. Bernhart, Siras Hakobyan, Arsen Arakelyan, Henry Loeffler-Wirth, Hans Binder

Date Published: 3rd Sep 2021

Publication Type: Journal

SARS-CoV-2 detection by extraction-free qRT-PCR for massive and rapid COVID-19 diagnosis during a pandemic in Armenia

Abstract (Expand)

COVID-19 pandemic severely impacted the healthcare and economy on a global scale. It is widely recognized that mass testing is an efficient way to contain the spread of SARS-CoV-2 infection as well as … aid in the development of informed policies for disease management. However, the current COVID-19 worldwide infection rates increased the demand for rapid and reliable screening of infection. We compared the performance of qRT-PCR in direct heat-inactivated (H), heat-inactivated and pelleted (HC) samples against RNA in a group of 74 subjects (44 positive and 30 negative). Then we compared the sensitivity of HC in a larger group of 196 COVID-19 positive samples. Our study suggests that HC samples show higher accuracy for SARS-CoV-2 detection PCR assay compared to direct H (89 % vs 83 % of the detection in RNA). The sensitivity of detection using direct samples varied depending on the sample transport and storage media as well as the viral loads (as measured by qRT-PCR Ct levels). Altogether, all the data suggest that purified RNA provides more accurate results, however, direct sample testing with qRT-PCR may help to significantly increase testing capacity. Switching to the direct sample testing is justified if the number of tests is doubled at least.

Authors: Diana Avetyan, Andranik Chavushyan, Hovsep Ghazaryan, Ani Melkonyan, Ani Stepanyan, Roksana Zakharyan, Varduhi Hayrapetyan, Sofi Atshemyan, Gisane Khachatryan, Tamara Sirunyan, Suren Davitavyan, Gevorg Martirosyan, Gayane Melik-Andreasyan, Shushan Sargsyan, Armine Ghazazyan, Naira Aleksanyan, Xiushan Yin, Arsen Arakelyan

Date Published: No date defined

Publication Type: Journal

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