One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages

Abstract

The COVID-19 pandemic was officially declared on March 11^th, 2020. Since the very beginning, the spread of the virus has been tracked nearly in real-time by worldwide genome sequencing efforts. As of March 2021, more than 830,000 SARS-CoV-2 genomes have been uploaded in GISAID and this wealth of data allowed researchers to study the evolution of SARS-CoV-2 during this first pandemic year. In parallel, nomenclatures systems, often with poor consistency among each other, have been developed to designate emerging viral lineages. Despite general fears that the virus might mutate to become more virulent or transmissible, SARS-CoV-2 genetic diversity has remained relatively low during the first ~ 8 months of sustained human-to-human transmission. At the end of 2020/beginning of 2021, though, some alarming events started to raise concerns of possible changes in the evolutionary trajectory of the virus. Specifically, three new viral variants associated with extensive transmission have been described as variants of concern (VOC). These variants were first reported in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Their designation as VOCs was determined by an increase of local cases and by the high number of amino acid substitutions harboured by these lineages. This latter feature is reminiscent of viral sequences isolated from immunocompromised patients with long-term infection, suggesting a possible causal link. Here we review the events that led to the identification of these lineages, as well as emerging data concerning their possible implications for viral phenotypes, reinfection risk, vaccine efficiency and epidemic potential. Most of the available evidence is, to date, provisional, but still represents a starting point to uncover the potential threat posed by the VOCs. We also stress that genomic surveillance must be strengthened, especially in the wake of the vaccination campaigns.

Keywords: COVID-19; Diagnostic tests; Lineages; SARS-CoV-2; VACCINES; Variants.

Fig. 1

Mutations observed in emerging SARS-CoV-2 lineages, in mink clusters, and in immunocompromised patients with long-term infection. (A) Schematic representation of the coding regions of the SARS-CoV-2 genome. The furin cleavage site in the S protein is represented with an elongated red triangle. Mutations are represented with colored triangles, as per legend. Variants possibly associated with increased mortality were derived from a previous work (Hahn et al., 2020). Subjects with long-term infection were described in the following works: immunosuppressed individual treated with CP (Kemp et al., 2020), Immunocompromised individual with cancer and treated with CP (Avanzato et al., 2020), Immunocompromised individual treated with Regeneron (Choi et al., 2020), lymphoma patient (Bazykin et al., 2021). (B) Mutations found in lineages B.1.1.7 (orange), B.1.351 (blue), and P.1 (green) are mapped onto the three dimensional structure of the spike protein. Mutations shared by two lineages are in chocolate, those shared by three lineages in dark red. The 3D structure corresponds to Swissmodel P0DTC2, which includes amino acids that are disordered in the spike crystallographic structures. For clarity, mutations are mapped on one monomer only.

Fig. 2

Maximum likelihood phylogeny of 457 SARS-CoV-2 genomes. Twenty sequences belonging to lineages B.1.1.7, B.1.351, P.1, P.2, B.1.1.28, B.1.375, and B.1.429 were downloaded from GSAID. The complete genomes of 16 cluster V viruses were also obtained, together with 300 randomly selected SARS-CoV-2 genomes collected from January 2020 to March 2021 (Supplementary Acknowledgement Table). In particular, 20 sequences/month were included. Sequence alignments were generated using MAFFT (v7.427) (Katoh et al., 2019; Polack et al., 2020; Walsh et al., 2020) The phylogenetic tree was constructed using RAxMLversion 8.2.12 (Stamatakis, 2014) and visualized with FigTree (http://tree.bio.ed.ac.uk/).

Fig. 3

Number of complete SARS-CoV-2 genomes sequenced in different countries. Data on 836,000 high-quality, complete genomes were retrieved from GISAID (https://www.gisaid.org/). Countries are colored according to the number of sequenced genomes, as per legend.

Fig. 4

Relationships between amino acid substitutions and conformational epitopes in the SARS-CoV-2 spike proteins. Conformational epitope may induce the neutralizing antibody against various viruses (Aso et al., 2019). Therefore, to estimate the vaccine's efficacy, the relationships between conformational epitopes and amino acid substitutions of the S protein in the B.1.1.7 and B.1.351 lineages were examined. Detailed procedures of these examinations were made as previously described (Aso et al., 2019). The changes detected in the two lineages (red) affected partially overlapping epitopes (blue). Particularly, amino acid substitutions (E484K and N501Y) in conformational epitopes were found in the RBD of the S protein (yellow). Reports suggested that amino acid substitutions of the conformational epitopes lead to viral reinfection and changes of vaccine efficacy (Russi et al., 2018). Thus, our in silico study suggests that the mRNA vaccine efficacy partially changes against the variants (Russi et al., 2018; Sahin et al., 2020), although this should also be examined in vitro and in vivo.