Deprivation Binge

Application of omics technology to combat the COVID‐19 pandemic

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As the COVID-19 pandemic spread, more and more mutations were detected in newly isolated SARS-CoV-2 strains, indicating adaptive viral evolution.18 Further, currently licensed vaccines are mainly designed for the original version of S protein; however, if they can still be protective against newly emerging SARS-CoV-2 mutant S protein is still dubious.19 On this basis, the disclosure of enough SARA-CoV-2 genomes for genomic surveillance is of great importance to track the mutations, evolution, and adaptation of SARS-CoV-2,6, 20, 21 and series of efforts were made to realize real-time genomic surveillance.22, 23

2.1 Genomic surveillance of SARS-CoV-2

The ongoing evolution of SARS-CoV-2 has been the topic of considerable interest as the pandemic spreading globally.24 Once a new prevalent variant arises in one country, it will quickly become a threat to neighbors.25 Evidence is growing that SARS-CoV-2 variants could evade immune responses under the selective pressure triggered by vaccines and previous infections, and new variants are being detected more frequently.6 Therefore, the strength and duration of both natural and vaccinal SARS-CoV-2 immunity remains will play a central role in shaping the future dynamics of COVID-19 cases and drowned a global rush to increase genomic surveillance.9

As the progression of COVID-19 pandemic, genomic surveillance has contributed significantly in tracking variants. Series of newly emerging variants are identified for further study, including B.1.1.7 (also called Alpha variant), B.1.351 (also called Beta variant), P.1 (B.1.1.28.1, also called Gamma variant), B.1.167.2 (also called Delta variant), B.1.427/B.1.429 (CAL.20C, also called Epsilon variant), P.2 (B.1.1.28.2, also called Zeta variant), B.1.525 (also called Eta variant), P.3 (B.1.1.28.3, also called Theta variant), B.1.526 (also called Lota variant), B.1.167.1 (also called Kappa variant), C.37 (also called Lambda variant), and some other variants spread in different regions.2631 Among them, B.1.1.7 variant, B.1.351 variant, P.1 variant, and B.1.617.2 were designated as variants of concern (VOCs).32

The SARS-CoV-2 B.1.1.7 variant originated in the UK from late Summer to early Autumn 2020. Recently, it has rapidly spread from southeast England to the whole world (at least 185 countries, territories, and areas), indicating a substantial selective advantage over other currently circulating lineages.33, 34 Increased transmissibility, risk of hospitalization, and reinfection add urgency to intensive monitoring of B.1.1.7 variant.19, 35, 36 The signature mutation N501Y may be partially responsible for the phenomenon.3739

B.1.351, the main lineage circulating widely in South Africa during the second wave of infections, is characterized by eight lineage-defining mutations in S protein of SARS-CoV-2, including K417N, E484K, and N501Y on the RBD, L18F, D80A, D215G, ∆ 242–244 on the NTD and A701V located in S2 region.6, 38 Since its appearance, the B.1.351 lineage almost completely displaced other lineages. They could be 50% more transmissible than the other circulating variants.40 Additionally, the researchers found that B.1.351 was more resistant to convalescent serum and vaccine-induced sera than other circulating variants in the pandemic.4143

The emergence of SARS-CoV-2 P.1 variant (B.1.1.28.1) was observed in a surge in severe COVID-19 case hospitalizations in Brazil in February, 2021. Through whole-genome sequencing, the P.1 lineage was revealed to be associated with rapid increase of confirmed cases and hospitalization rates.44, 45 This new P.1 lineage bearing 17 mutations, including 11 mutations on the S protein. These mutations resulted in increased binding to the human angiotensin-converting enzyme 2 (ACE2) receptor and immunity evasion against multiple neutralizing monoclonal antibodies, convalescent plasma, and vaccinee sera, which will threaten current antibody therapies and lead to increased reinfection rates.46, 47 P.2 variant (B.1.1.28.2) is a sub-lineage of B.1.1.28, which distinguished from P.1 for the single mutation E484K on the RBD of S protein. This variant was first reported in Rio de Janeiro, and then spread to the others states of Brazil.48, 49 P.3 variant (B.1.1.28.3), which carried N501Y and E484K on the RBD of S protein, is another sub-lineage prevalent in Philippines.50, 51

The recently emerging variants almost all carried the L452R mutation, including B.1.427/B.1.429 variant, B.1.526 variant, and B.1.167 variant. B.1.427/B.1.429 variant (also CAL.20C), first identified variant bearing a L452R mutation, is the prevalent lineage spread in California, USA, which possesses increased infectivity and resistance of neutralization due to the cooccurrence of L452R, S13I, and W152C mutation.30, 52, 53 B.1.526 variant was identified in New York City in November 2020, accompanied by controversial breakthrough infection.5456 SARS-CoV-2 B.1.167.1 is one of the circulating variants of India, which had spread worldwide.57 B.1.167.2, also known as Delta variant, is first detected in the United Kingdom in April, 2021, and subsequently, the emergence of this variant was traced back to October, 2020 in India. As of August 10, 2021, it has been reported by over 140 countries, territories, and areas around the world.58 B.1.167.2 carries T19R, ∆157-158, L452R, T478K, D614G, P681R, and D950N mutations on the S protein, indicating high transmissibility and breakthrough infection of vaccinated people, as well as increased hospitalized patients.28, 57, 59

Apart from VOCs, series of emerging variants have been monitored for further alerts. A.23.1 is a sub-lineage of A.23 defined by F157L, V367F, Q613H, and P681R mutations, possessing increased fusion activity and immune evasion ability. In January, 2021, A.23.1 overtook the former circulating variants in Uganda, and spread rapidly to more than 23 countries.31 R.1 variants is a lineage first detected in USA and Europe, which rapidly prevailed in Tokyo in March, 2021.60 And B.1.525 (also called Eta variant), which charactered by the carrying of signature mutations of VOCs, is first identified in Nigeria and poses incredible risk on unvaccinated population in Africa. Also, the possible resistance to vaccine-induced immunity will facilitate its worldwide spreading.61, 62 Lambda variants (C.37), carrying L452Q and T859N, are circulating in Peru during January to April, 2021 and could be responsible for the steep increase of confirmed cases in South America. As reported, L452Q and D614G are considered to increase the transmissibility, and T859N could be responsible for a reduced neutralization by monoclonal antibodies and by convalescent and postvaccination sera (Table 1).29

TABLE 1.
Mutations on the S protein of circulating SARS-CoV-2 variants

Variants Mutations on S protein Signature mutations References
Alphaa

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