Evolution of the SARS-CoV-2 genome and emergence of variants of concern.

The high transmission and mortality rates associated with SARS-CoV-2 have led to tragic consequences worldwide. Large-scale whole-genome sequencing of the SARS-CoV-2 genome since its identification in late 2019 has identified many sequence changes and the emergence of novel strains, each described by co-segregation of a particular set of sequence variations. Variants designated G, alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) are important lineages that emerged sequentially and are considered variants of concern. A notable feature of the last four, each of which ultimately evolved from clade G, is the large number (≥ 20) of co-segregating sequence variations associated with them. Several variations are in the spike gene, and some variations are shared among or between strains. Meanwhile, observation of recurrent infections with the same or different SARS-CoV-2 lineages has raised concerns about the duration of the immune responses induced by the initial infection or the vaccine that was administered. While the alpha strain is sensitive to immune responses induced by earlier strains, the beta, gamma, and delta strains can escape antibody neutralization. Apart from random replication errors, intra-host RNA editing, chronic infections, and recombination are processes that may promote the accumulation of sequence changes in the SARS-CoV-2 genome. The known contribution of recombination to coronavirus evolution and recent data pertaining to SARS-CoV-2 suggest that recombination may be particularly important. Continued surveillance of the SARS-CoV-2 genome is imperative.

Evolution of SARS-CoV-2 genome from December 2019 to late March 2020: Emerged haplotypes and informative Tag nucleotide variations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious disease in humans. First identified in November/December 2019 in China, it has rapidly spread worldwide. We analyzed 2790 SARS-CoV-2 genome sequences from 56 countries that were available on April 2, 2020, to assess the evolution of the virus during this early phase of its expansion. We aimed to assess sequence variations that had evolved in virus genomes, giving the greatest attention to the S gene. We also aimed to identify haplotypes that the variations may define and consider their geographic and chronologic distribution. Variations at 1930 positions that together cause 1203 amino acid changes were identified. The frequencies of changes normalized to the lengths of genes and encoded proteins were relatively high in ORF3a and relatively low in M. A variation that causes an Asp614Gly near the receptor-binding domain of S were found at a high frequency, and it was considered that this may contribute to the rapid spread of viruses with this variation. Our most important findings relate to haplotypes. Sixty-six haplotypes that constitute thirteen haplotype groups (H1-H13) were identified, and 84.6% of the 2790 sequences analyzed were associated with these haplotypes. The majority of the sequences (75.1%) were associated with haplotype groups H1-H3. The distribution pattern of the haplotype groups differed in various geographic regions. A few were country/territory specific. The location and time of emergence of some haplotypes are discussed. Importantly, nucleotide variations that define the various haplotypes and Tag/signature variations for most of the haplotypes are reported. The practical applications of these variations are discussed.

Study on SARS-CoV-2 strains in Iran reveals potential contribution of co-infection with and recombination between different strains to the emergence of new strains.

We aimed to describe SARS-CoV-2 strains in Iranians from nine distributed cities infected during two months expanding late 2020 and early 2021 by genotyping known informative single nucleotide in five PCR amplicons. Two variants associated with haplotype H1 (clade G) and nine additional variants associated with other haplotypes were genotyped, respectively, in RNA isolates of 244 and 85 individuals. The variants associated with the H1a (GR) and H1b (GH) haplotypes were most prevalent, indicating a significant change in infection pattern with passage of time. The most important findings were that recombinant genomes and co-infection, respectively, were surmised in 44.7% and 12.9% of the samples extensively genotyped. Partners of many of the recombinations were relatively common strains. Co-existing viruses were among those currently circulating in Iran. In addition to random mutations, co-infection with different existing strains and recombination between their genomes may significantly contribute to the emergence of new SARS-CoV-2 strains.

World-wide tracking of major SARS-CoV-2 genome haplotypes in sequences of June 1 to November 15, 2020 and discovery of rapid expansion of a new haplotype.

Earlier, 13 haplotype groups defined by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequence variations were identified in 2790 sequences available in March 2020. Also, 23403A>G that causes p. Asp614Gly in the spike protein and is one of the defining variations of the haplotype group H1, was becoming increasingly prevalent. As a follow-up, 74922 SARS-CoV-2 sequences retrieved from individuals infected in June 1 to November 15 were analyzed. Consistent with the reports on 23403A>G, H1 haplotype frequency increased world-wide; among August to November sequences, only 0.3% were associated with non-H1 haplotypes. This finding prompted assessment of H1 sub-haplotypes among the sequences of the later stage of the coronavirus disease 2019 pandemic. The distribution of the sub-haplotypes differed in different regions, but 98.4% of the sequences were associated with five H1 sub-haplotypes. One of these had not been previously observed and had emerged in Europe by June 2020. The most important finding of the present study is identification of this new sub-haplotype (H1r) and finding evidence that suggest it may have a high potential for expansion. Its frequency had reached 10%-90% in various countries/territories of Europe by the end of September. The new sub-haplotype is defined by seven sequence variations, one of which causes Ala222Val in the spike protein.