Recently world fights with the newly emerged coronavirus family member, SARS-CoV-2 and disease are COVID-19 [1, 2, 32]. In recent studies shown that actual therapy against the disease is limited. Antivirals, such as remdesivir and nirmatrelvir-ritonavir, have proved to be most useful earlier in illness and for less severe disease. Immunomodulatory therapies, such as dexamethasone and interleukin-6 or Janus kinase inhibitors, are most useful in severe disease or critical illness [33]. Thus, diagnosis of the disease was the main starting point. Up to now, sequence analysis has been utilized however which are time-consuming and require special instruments and specialized experts. Therefore, RT-PCR is preferred as a gold standard method to detect the diagnosis and follow-up of the COVID-19 disease [34].
Many different types of SARS-CoV-2 variants are described such as Alpha, Epsilon, Gamma, B.1.1.7 (U.K.), Brazil, Delta or even Kappa variants [35]. The genetic variability of SARS-CoV-2 determined the accumulation of mutations over time, influencing transmission, severity of disease, and vaccination efficacy [36, 37]. Since the beginning of the pandemic, clinical and demographic characteristics linked to sequence information were noted to better understand outbreak episodes and local dynamic evolution [38, 39]. The US CDC has been categorized variants of concerns as a variant with one or more mutations which is important to understand how the virus infects people easily and spreads from person to person. If the SARS-CoV-2 variant has a clear association with unusual events, it is called a VOC, and if the variant is still being investigated for its association with unusual events, it is called a VOI. B.1.1.7, also known as the British variant, contains an unusually high mutation rate. This feature provides this variant with high contagiousness [28, 29, 37]. It has been reported that this variant has little evasion effect from post-vaccine neutralizing antibodies for all vaccines [40].
The unaware of their COVID-19 status are actual problem for the virus transmission which is highly related with the mutations and variants of the SARS-CoV-2. SARS-CoV-2 has showed increased mutations rates encourage its spread that provide it to spread in the face of rising population immunity while maintaining their replication fitness. Sequence analysis reported most of the mutation is found in the spike protein of the virus [41].
Additionally, D614G; the RBD mutation N501Y; the RBD mutation E484K; other RBD mutations; NTD mutations; mutations proximal to the S1/S2 furin cleavage site; and non- spike mutations are demonstrated with several [35]. Thus, SARS-CoV-2 variants are classified according to their lineage and component mutations [1, 17, 42].
The variants of SARS-CoV-2 is classified by transmissibility, disease severity the response to vaccination by produced immunoglobulin IgG antibody, reduced effectiveness of treatments, or diagnostic detection failures, and termed as VOC or VOI [43,44,45].
In the early 2020, India, two actual variant was emerged sharing with common ancestor as Delta (B.1.617.2) and Kappa (B.1.617.1) [44]. In the United States, the Delta variant was first identified in March 2021 and after a while Delta plus is described [45]. These variants show mutations as L452R in RBD region, P681R in roximal furin cleavage site, and other various mutations within orf3, orf7a, and the nucleocapsid gene [46]. While B.1.617.1 included the RBD mutation (E484Q), the B.1.617.2 showed the RBD mutation (T478K) [35].
According to the US CDC data, signature Spike mutations in the aggregated Delta and Delta Plus variant include T19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, and D950N [47]. Especially, B.1.617.2 of SARS-CoV-2 shows the high transmission ability, and low vaccine coverage in which 54 countries are affected rapidly [48].
Recent studies reported that both vaccinated and unvaccinated infected people demonstrate similar Delta viral loads. Alpha, Beta, Gamma, Delta, Delta Plus, Epsilon, Eta, Theta, Iota, Kappa, and Lambda are listed in these variant class [49]. These questions recalled whether vaccination controls Delta spread as effectively.
By late November of 2020, the Epsilon (B.1.429/B.1.427) lineage raised in the US state of California. The sequence analyses are reported that the epsilon variant is defined with 4 additional amino acid mutations, including two spike protein mutations, S13I and W152C, located in the signal peptide and N-terminal domain, respectively [50]. Additionally, L452R and S13I/W152C mutations were found Epsilon variant [51]. On the other side, in 2021 March, new variant is described termed with lineage B.1.617.1 and then the Kappa variant of interest by the WHO. Generally, E484Q, L452R and P681R co-mutation in the Spike glycoprotein (S protein) is observed with this variant. Additionally, it is termed as co-mutation of L452R and P681R [52].
Kappa variant emerged ~ 35% of all sequenced cases in India. Although the multiple mutations are found in S protein of the virus to increase the viral fitness, variant has not dominantly spread globally. Kappa and Delta variants share the identical substitutional mutation (L452R) [53]. The mutations were observed at similar positions (484) in Kappa, Beta and Gamma, with differing amino acid changes [54]. Thus, the meaning of these mutations is very important to understand the transmission capacity of the COVID-19 disease, pandemic episode, and diagnosis of the virus with mutation types.
The Nucleocapsid (N) D3L mutation of B.1.1.7 is lineage specific and is used for detection of this variant. The E484K mutation significantly reduces antibody neutralization. This mutation significantly increased the transmission rate of SARS-CoV-2 in America and India. It has also been reported that this mutation has the effect of avoiding neutralizing antibodies formed after BNT162b2 vaccination. The basic reproduction number (R0), is intended to be an indicator of the contagiousness or transmissibility of infectious and parasitic agents. R0 number of B.1.617.2, which is the average number of people who will contract a contagious disease from one person with that disease, is between 5 and 8. These means that if R0 > 1, the epidemic will grow, and if R0 < 1, the epidemic will reverse [55]. Variants containing the E484K mutation (such as the Beta and Gamma variants), reduced neutralization of post-vaccine sera, whereas there was a minimal effect on the Alpha variant. Garcia-Beltran et al. utilized a lentiviral vector-based SARS-CoV-2 pseudovirus neutralization assay and compared the neutralizing capacity of BNT162b2 vaccine and mRNA-1273 vaccine post-vaccination sera against SARS-CoV-2 variants of interest or concern [56]. In conclusion, studies on post-vaccine sera showed that E484K alone, or combined with other mutations or variants containing E484K, reduced the neutralization titer, regardless of the vaccine platform used in different studies [57,58,59,60]. Due to the availability of L452R and E484Q mutations, the B.1.617.1 has showed high capability to evade humoral immunity than B.1.617.2 [59].
Additionally, it exhibits reduced susceptibility to “Casirivimab” and to “Bamlanivimab”. B.1.617.2 were lower in ChAdOx1 vaccines than in BNT162b2 vaccine while B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1 [60]. The UK has been exhibited a high vaccination ratio. However, although there was high vaccination coverage, the B.1.617.2 variant spread dominantly and rapidly. Spread ability of Delta variant has been higher than Alpha and Epsilon variant as 90%, globally [57]. Some medical experts supposed that the actual problem of high transmission ability of B.1.617.2 variant could be related to the country’s decision to delay second doses of vaccine.
Lopez Bernal et al. were explained that one dose of either the Pfizer-BioNTech BNT162b2 vaccine or the AstraZeneca-Oxford ChAdOx1 nCoV-19 vaccine is insufficient to conserve against symptomatic infection with the B.1.617.2 variant. On the other hand, two doses showed the effectivity to 88% and 67%, respectively with these two vaccines which are still lower protection against than Alpha variant offered by both vaccines [61].
The present version PCR assays, regularly desired with inside the initial detection of SARS-CoV-2 mutations, permit the prediction of lines that want to be showed via way of means of NGS [62]. Alpha (September 2020), Beta (May 2020), Gamma (November 2020), and Delta (October 2020) were previously circulating VOCs, while Omicron (November 2021) is the only VOCs in circulation on the World [30].
In Türkiye, the most common lineages were found as B.1.1.7, B.1.617.2, B.1.1.529, and B.1.1.529.1 by Sayan et al. [62] from April 2021 to February 2022. According to Sayan’s Study, In September 2021, B.1.617.2 lineage (n = 28, 100%) were the dominant in Turkiye. Other lineages were not detected among the sequenced strains. In Turkiye, Delta was circulating in December 2021 with a higher rate (n = 27, 84%) while a new strain named Omicron (n = 5, 16%) was reported for the first time in the same month [62].
In May 2021, the prevalent variant circulating in Turkiye was Alpha (B.1.1.7), followed by the Beta (B.1.351) and Gamma (P.1) VOCs and, by a low percentage, of the Epsilon (B.1.427 and B.1.429) VOI [24]. In June 2021, COVID-19 cases increased rapidly (around four million subjects infected) and over 40,000 deaths were observed [23]. The hallmark of the fourth wave was the appearance of the Delta (B.1.617.2) lineages [63]. In August 2021, more than 20,000 people were infected per day in Turkiye [26]. Delta variant dominated the epidemic worldwide until Omicron emerged in November 2021 [64].
In this study, during the investigation of variant types of SARS-CoV-2, the British variant is raised first, followed by the Delta, B.1.351 (South Afica/Brasil) variant between January 1 and November 30 2021 in Istanbul population.
In this study, The “E484K Variant” is considered a rare variant/mutation in the early period of the pandemic. The E484K mutation is no longer a rare and has been detected in several lineages and VOCs in the later period of pandemic. The frequencies are obtained as SARS-CoV-2 positive as 66.1% (115.899) and B.1.1.7 Variant as 23.2% (40.686), Delta Variant (L452R) as 9.8% (17.182), B.1.351 variant as 0.8% (1.370) and E484K as 0.1% (230) in our study.
To understand the transmission ability of the COVID-19 disease, variants are important starting point. Herein, we evaluate the four main type of the variant varieties. In April 2021, SARS-CoV-2 positive patients are dominantly observed and same time B.1.1.7 variant of the SARS-CoV-2. However, after the June 2021, B.1.1.7 variant has declined, and November 2021 ratios has been zero. Up to July 2021, Delta variant (L452R) has been not observed. It has been increasing since September-2021 and October 2021 is the higher point of the transmission of Delta Mutation Variant (L452R). B.1.351 variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. After the July 2021, the variant has been observed with a decline. On the other hand, E484K has not been observed up to July 2021 as L452R variant and September 2021 is the pick point. Up to end of the October 2021, there was a fluctuation for this variant type. When the gender type is compared within the variants, women were found to be more prevalent in all varieties. As of June 2021, detection of variants is insufficient.
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