**1. Introduction**

COVID-19 has been declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. For the short time period, the COVID-19 time has passed in a few

countries throughout the past 2 years of the pandemic, but there has been a new infection outbreak recorded in a few continents, and it has spread quickly globally, causing new waves in many countries. According to the WHO, as of today, June 22nd, a total of 6,544,553 new infections have been reported worldwide in just 24 hours. All viruses, including SARS-CoV-2, mutate over time, and high mutation rates have been linked to improved replication fitness and evolvability. These characteristics give RNA viruses a high level of adaptability. As a result, RNA viruses adapt quickly to changing environmental conditions [1, 2]. The genomes of RNA viruses, including coronavirus, are prone to mutation in three different ways. The first is due to the low fidelity and proof-reading activity of RNA polymerase, which results in the erroneous incorporation of mutations during replication. The second is due to a recombinational event between two viral lineages, and the third is due to the host RNA editing system. Mutations may be neutral, beneficial, or deleterious. Although the majority of circulating RNA virus mutations are neutral, some may affect viral replication and infectivity [3–5]. The COVID-19 pandemic's longevity could lead to the accumulation of immunologically important mutations in the viral genome that provide the virus an edge in its ability to replicate and survive [6, 7]. In most RNA viruses, RNA polymerase lacks proofreading activity [8, 9]. Mutations in the surface protein can significantly alter viral function and/or interactions with neutralising antibodies. Spike protein receptor-binding domain (RBD) mutations in the SARS-CoV-2 genome are being studied for their potential impact on infectivity and antibody resistance caused by this new variant. This is because the RBD on the S protein of SARS-COV-2 facilitates binding between the S protein and the host angiotensin-converting enzyme 2 (ACE2). S-ACE2 binding allows SARS-CoV-2 to enter the host cell and begin the viral infection process [10, 11]. SARS-CoV-2 infection is only detected in humans, and there have been numerous reports of mutations in the gene that codes for the Spike (S) protein [5, 7, 12, 13]. Since the COVID-19 pandemic disease outbreak, mutations have been reported in 96.5 percent of the SARS-CoV-2 spike protein's amino acid residues [14]. The use of vaccines is the only method for treating the viral pandemic, and several COVID-19 vaccines have been rolled out globally to stop the spread of sickness. However, like other vaccines, these ones are also not 100% effective, and as a result of the SARS-CoV-2 breakthrough infection, vaccine recipients are now being diagnosed with COVID-19. However, despite breakthrough infection, vaccines are still effective in treating serious illnesses linked with COVID-19 [15–17]. A number of variants of SARS-CoV-2 have been reported worldwide since the first reports of pandemics. The World Health Organisation classified some of them as variants of concern because they are extremely contagious and frequently lead to breakthrough infections. VOCs have the ability to neutralise the effects of numerous vaccinations. These are the causes of recent waves and breakthrough infections in various countries. Variants of Concern (VOCs) are an emerging topic of research since they can alter the transmissibility, clinical presentation, and severity of the disease, as well as have an effect on treatment options such as medicines and vaccines.

### **2. Emergence of variants of concern (VOCs) of SARS-CoV-2**

Several variations in the SARS-CoV-2 genome have been reported in the last 2 years of the pandemic. Spike proteins, an outward projection of the SARS-surface, CoV-2's interacted with ACE-2 receptors on host cells, resulting in viral pathogenesis. Since the beginning of the pandemic, the amino acids of spike protein have been mutated, and a large number of variations have emerged. A few variations have been linked to viral replication fitness and survival advantages, which ultimately

*Perspective Chapter: Emerging SARS-CoV-2 Variants of Concern (VOCs) and Their Impact… DOI: http://dx.doi.org/10.5772/intechopen.107844*

#### **Figure 1.**

*Schematic representation of emergence of VOCs of SARS-CoV-2 during last 2 years of pandemic and their impact on COVID-19 risk.*

increases the risk of disease transmission and severity in the human population (**Figure 1**). Furthermore, a few variants are highly transmissible and less susceptible to vaccine-induced and infection-induced immune responses, causing breakthrough infections. Based on this, the World Health Organisation classified a few SARS-CoV-2 virus variants as Variants of Concern (**Table 1**). This chapter discussed how VOCs have posed health risks to the human population in the last 2 years.

## **2.1 Impact of the alpha variant (B.1.1.7 & Q lineages) on the severity and spread of the disease**

The alpha variant was the first variant of concern for SARS-CoV-2 after the induction of the pandemic in March 2020. The first case of the alpha variant was detected in October 2020 in the United Kingdom and subsequently spread to many countries, causing an outbreak. The WHO labelled the variant as an alpha and in lineage B.1.1.7. The alpha spike protein contains non-synonymous mutations and deletions, including deletions 69–70, 144, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H, and each mutation has its own biological significance, which increases overall infectivity [29]. The alpha variant spread rapidly in the UK in Oct-Dec 2020 and the most frequently observed mutation was the N501Y mutation in spike protein. The substitution



#### **Table 1.**

*Variant of concerns, notable mutations in SARS-CoV-2 spike and their impact on viral replication fitness and survival advantages over original SARS-CoV-2 virus.*

of tyrosine for asparagine at position 501 of spike protein increases its affinity for ACE-2 receptors on host cells. [30], as results increase in transmission rate, which derived the first wave of COVID-19 in many countries. A strain carrying D614G in RBD domains is more infective and resistant to some neutralising antibodies, which has obvious implications for COVID-19 patient recovery [31]. According to studies, the G614 variant has a greater number of functional spikes on its surface than the D614 variant. Furthermore, it has been shown that the D614G mutation stabilises the interaction between the S1 and S2 domains and limits S1 shedding, resulting in increased overall infectivity [32].

#### *2.1.1 Transmission and hospitalisation*

It originated in the UK, but the variant was present on all continents within 2 months of its emergence. As of December 2020 [33], B.1.1.7 was the cause of two-thirds *Perspective Chapter: Emerging SARS-CoV-2 Variants of Concern (VOCs) and Their Impact… DOI: http://dx.doi.org/10.5772/intechopen.107844*

of COVID-19 infections in the UK and one-quarter of all cases worldwide as of December 2020 [34]. The emergence of alpha variants resulted in an increase in the transmission rate and hospitalisation of COVID-19 cases, as few studies estimated the infection rate and it was 45–71% higher in the alpha variants than in the original virus [19, 34, 35]. SARS-CoV-2 lineage B.1.1.7 infection was linked to an increased risk of hospitalisation. Bager et al. discovered in 2021 that the hospitalisation rate in alpha variants rises over time. They enrolled 50,958 COVID-19 patients, of whom 30,572 had their SARS-CoV-2 genome sequenced, and followed up with 14 days of hospitalisation data. The Alpha variant infected 34.5 percent of all patients and hospitalised 6.4 percent. 29.4 percent of the hospitalised patients were infected with Alpha, while 70.6 percent were infected with other strains. During the study period, the number of COVID-19 hospitalizations decreased, but the proportion of patients with the Alpha variant increased dramatically, from 3.5 percent in week 1 to 92.1 percent in week 10 [36]. Veneti et al. included 27,753 COVID-19 patients in their study, of whom 23,169 are cases of alpha variant. Study showed that the B.1.1.7 was linked with a 1.9-fold increased risk of hospitalisation and a 1.8-fold increased risk of ICU admission, in comparison to non-alpha strain [37]. Several studies showed that the emergence of the alpha variant was linked to an increase in transmission risk and hospitalisation rate [19, 38].

#### *2.1.2 Vaccine response*

According to studies, vaccinated people are less likely to be hospitalised than unvaccinated people. According to Eyre et al., vaccinated individuals infected with alpha variants had a lower transmission and hospitalisation rate [39]. Study of Lopez et al. in UK population infected with alpha variant showed that the one dose of BNT162b2 and ChAdOx1 nCoV-19 (AstraZeneca) vaccine was found to be effective against 48.7% (95% CI, 45.5–51.7) symptomatic alpha variant infection, whereas effectiveness increased to 93.7% (95% CI, 91.6–95.3) and 74.5% (95% CI, 68.4–79.4), respectively, after second dose of administration BNT162b2 and ChAdOx1 nCoV-19 (AstraZeneca) vaccine [40]. A similar study conducted by Chemaitelly et al. showed that the mRNA-1273 vaccines were effective 88.1% (95% CI, 83.7–91.5) after the first dose, whereas it was found to be 100% (95% CI, 91.8–100) after the second dose of administration [41]. Mahase et al. also evaluated the effectiveness of the Novavax vaccine, and it was found to be 85.6% effective against symptomatic COVID-19 with the alpha variant [42].

#### **2.2 Impact of the beta variant (B.1.351) on the severity and spread of the disease**

The beta form was first discovered in South Africa, and primarily infected young people with no disease severity risk. This variant was responsible for more than 90% of all cases and the 2nd wave of COVID-19 in South Africa in the last month of 2020 [43], and spread to other African countries, Asia, Australia, and North and Central America [44]. Among several structural and non-structural mutations in beta spike, K417N, E484K, and N501Y are the three critical changes that could give SARS-CoV-2 viral fitness and survival advantages over the circulating strains in the same region where it was common [44].

#### *2.2.1 Transmission and hospitalisation*

Studies showed that the beta variant is comparatively highly transmissible than that of earlier circulating strain of SARS-CoV-2. In 2021, Pearson et al. demonstrated that prior exposure only partially protects against beta variant infection, and it has been

accounted for about 40% of new SARS-CoV-2 infections compared to only 20% for Alpha variants in the prevalent area. As estimated 501Y.V2 is 1.50 times as transmissible as previously circulating variants [45]. Studies showed that the person infected with beta variant has higher risk for disease severity than the alpha variant. The study of Veneti et al. showed that the B.1.351 was associated with a 2.4-fold increased risk of hospitalisation and a 2.7-fold increased risk of ICU admission compared to non-VOC [20].

#### *2.2.2 Vaccine response and breakthrough infections*

Studies showed that the efficacy of vaccines is greatly reduced when dealing with the beta variants. In a study conducted by Garcia-Beltran et al. in 2021, the B.1.351 variant significantly reduced neutralisation even in fully vaccinated individuals with BNT162b2 and mRNA-1273 vaccines, whereas protection for other circulatory strains remained constant during the same period [21]. Wu et al. showed that the B.1.351 reduced the neutralisation efficiency of the mRNA-1273 vaccine but that it was still effective to neutralise the B.1.351 virus in fully vaccinated individuals [46]. Mahase, stated that the Novavax was 60% effective against the B.1.351 variants and 95.6% effective against the original SARS-CoV-2 virus [42].
