Molecular Epidemiology of SARS-CoV-2 Omicron Sub-Lineages Isolated from Turkish Patients Infected with COVID-19

Abstract

Early detection and characterization of new variants and their impacts enable improved genomic surveillance. This study aims to evaluate the subvariant distribution of Omicron strains isolated from Turkish cases to determine the rate of antiviral resistance of RdRp and 3CLpro inhibitors. The Stanford University Coronavirus Antiviral & Resistance Database online tool was used for variant analyses of the strains uploaded to GISAID as Omicron (n = 20.959) between January 2021 and February,2023. Out of 288 different Omicron subvariants, B.1, BA.1, BA.2, BA.4, BE.1, BF.1, BM.1, BN.1, BQ.1, CK.1, CL.1, and XBB.1 were the main determined subvariants, and BA.1 (34.7%), BA.2 (30.8%), and BA.5 (23.6%) were reported most frequently. RdRp and 3CLPro-related resistance mutations were determined in n = 150, 0.72% sequences, while the rates of resistance against RdRp and 3CLpro inhibitors were reported at 0.1% and 0.6%, respectively. Mutations that were previously associated with a reduced susceptibility to remdesivir, nirmatrelvir/r, and ensitrelvir were most frequently detected in BA.2 (51.3%). The mutations detected at the highest rate were A449A/D/G/V (10.5%), T21I (10%), and L50L/F/I/V (6%). Our findings suggest that continuous monitoring of variants, due to the diversity of Omicron lineages, is necessary for global risk assessment. Although drug-resistant mutations do not pose a threat, the tracking of drug mutations will be necessary due to variant heterogenicity.

Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019

“…The T21I mutation on the BF.11.1 virus increased the IC 50 values 3.8 fold, consistent with the degree of nirmatrelvir resistance when other SARS-CoV-2 lineages acquired the T21I mutation in vitro [11,12]. Based on GISAID data, the probability of having at least one or more mutations in the 3CL protease is 0.5-0.6% during the Omicron strain epidemic, of which T21I is one of the most frequent genetic mutations [17,18]. Additionally, the frequency of this mutation has been reported to show no apparent increasing trend as of 1 year after the launch of nirmatrelvir [17].…”

Molecular epidemiology of SARS‐CoV‐2 variants in circulation in the state of Maranhão, Brazil

“…Omicron's BA.1 lineage and its sub‐lineages corresponded to 42.8% of the sequenced genomes (145 genomes) in the present study (with emphasis on BA.1.14 and BA.1.14.1 sub‐lineages). The sub‐lineage BA.1.14 was widely reported in different parts of the world in the first half of 2021, being evidenced in about 82 countries with varied prevalence 26–28 . In Brazil, the distribution of these sub‐lineages remained constant throughout the first half of 2021, with the same trend in the number of sequenced genomes in the different geographic regions of the country 29,30 .…”

“…The new variant of SARS-CoV-2 quickly crossed international borders and by December 9, 2021, it had already been reported in 57 countries. 19,20 In Brazil, the Omicron variant was introduced in mid-December 2021, and by the end of [26][27][28] In Brazil, the distribution of these sublineages remained constant throughout the first half of 2021, with the same trend in the number of sequenced genomes in the different geographic regions of the country. 29,30 Study carried out between October 2021 and April 2022 with genomes from all over Brazil, showed the BA.1, BA.1.1 and BA.1.14.1 sub-lineages as the most prevalent and pointed out that Omicron was imported mainly by the state of São Paulo, which in turn dispersed the lineages to other states and regions of the country.…”