**2.3 Impact of the gamma (P.1 and descendent lineages) on the severity and spread of the disease**

The first case of the gamma variant was detected in Tokyo, Japan in Jan-2021 and patients were relocated from the Brazilian Amazon state. The WHO has classified the variant as a gamma and assigned it to lineage P.1. Ten of the non-synonymous defining mutations in the S gene are present in the gamma lineage, which evolved following a period of rapid genetic diversification. Of these changes, three (N501Y, E484K, and K417T) increased favourable stable interaction with the human ACE-2 receptor. This mutation caused an outbreak in the Manaus region of Brazil in December 2020, with gamma variant cases accounting for 42% of all cases [22].

#### *2.3.1 Transmission and hospitalisation*

In a study done in Brazil in the year 2021 by Chen and Lu, it was demonstrated that patients with gamma variations have high viral loads that are 10 times higher than those of patients with other lineages. Transmissibility and infectivity were twice higher than the other circulating strains in all age groups. Studies showed that the gamma variant can overcome the immunity developed from earlier infections, increasing the risk of a breakthrough infection. Additionally, the death rate was 10–80% greater in the group infected with the gamma variant [22]. A study by Funk et al. showed that gamma variant patients had significantly higher adjusted odds ratios for hospitalisation (2.6, 95% CI, 1.4–4.8) and ICU admission (2.2, 95% CI, 1.8–2.9) [47].

#### *2.3.2 Vaccine response and breakthroughs infection*

Studies revealed that the Gamma variant also had a decrease in anti-RBD antibody neutralisation, and it has been connected to reinfections and breakthrough infections in those who have received vaccinations [48–51]. The Gamma variant was found to reduce the antibody neutralising activity of Pfizer or Moderna vaccines, as the report showed the prevalence of breakthrough infections in fully vaccinated recipients. In

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

a 2021 study on fully vaccinated Gold Miners recipients in French Guiana, Vignier et al. showed that 60% of BNT162b2 vaccine recipients experienced breakthrough infection [52]. Wang et al. also demonstrated that gamma variants had a neutralising effect on multiple monoclonal antibodies and were more resistant to neutralisation by convalescent plasma and vaccinee sera. The gamma variant was estimated to be 3.8–4.8 times more resistant to BNT162b2 or mRNA-1273 vaccine recipients [23, 53].

### **2.4 Impact of the delta and delta+ (B.1.617) variants on the severity and spread of the disease**

The first instance of delta variations was discovered in India, and it was one of the most common SARS-CoV-2 variants that affected the majority of the world. Lineage B.1.617 was assigned to these variations. The L452R, T478K, D614G, and P681R are four of the 17 variations in the Delta variation that are of particular concern, due to their involvement in infectivity and transmission. In comparison to alpha, the infection and transmissibility rates were extremely high. Despite immunisation, this variation resulted in a large number of human deaths. L452R and E484Q is not found in the B.1.617.2 lineage [54, 55]. The B.1.617.2 lineage was first associated with infection in India, and the dominant variant in infection in the UK in 2021. It was highly infectious and spread more rapidly than the original version of the virus. A study conducted by Deng et al. showed that the mutation L425R in the California population resulted in an increase in the binding affinity of the spike protein of SARS-CoV-2 with ACE-2 host receptors, which increased the viral load and 20% transmission rate [56]. Few studies have shown that L452 is not directly linked with the host ACE-2 receptor. This mutation located in the RBD's hydrophobic plaques generates structural alterations that promote binding of spike protein with the ACE-2 receptor [57, 58]. In addition to this, there was 3–6 folds reduction in neutralisation capacity of vaccine elicited sera in experiments with pseudotyped virus (PV) particles [58]. Few studies demonstrated that the D614G mutation in the spike protein promotes viral multiplication in the upper respiratory tract and enhanced transmission rate [59, 60]. The P681R, which is a substitution at position 681, may increase the variant's celllevel infectivity [61, 62]. During outbreak of delta variants worldwide, a new variant was emerged in United Kingdom that carries a novel point mutation' K417N' in delta variant and designated as a delta plus. Lineage AY.1 or B.1.617.2.1 was assigned to this variant. The three most prominent mutation K417N, V70F, and W258L in spike were exclusively present in the Delta Plus variant [63]. Besides this, few other delta variants emerged, Delta-AY.2 in the USA and Delta-∆144 in Vietnam [64].

#### *2.4.1 Transmission and hospitalisation*

During the second wave of the pandemic, COVID-19 patients required more ICU time, oxygen, and non-invasive and invasive ventilatory support. According to estimates, hospital mortality in the second wave was double that of the first [65]. Ong et al. calculated the risk linked with the delta variant by observing the need for oxygen, ICU admission time, and death and found that delta was associated with increased disease severity when compared to non-VOCs [66]. Several studies revealed that a large percentage of vaccine recipients reported breakthrough infection during the delta variant wave [67–71]. Initial studies demonstrated that the delta variant increased the hospitalisation risk in the population, despite the first dosage of vaccination [24, 72, 73]. Non-vaccinated people and those who contacted viruses

within 14 days of vaccination were more prone to hospitalisation [74]. A similar study conducted by Twohig et al. showed delta variant infections linked to an increased hospitalisation rate (hazard ratio 226 [95% CI 132–389]) in comparison to alpha variant infections. All age categories experienced an increase in mortality during the Delta wave, with patients under 45 experiencing the most increase in infection (10.5 percent vs. 7.2 percent, p 0.001), compared to pre-Delta wave [24].
