The evolution of SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths and substantial morbidity worldwide. Intense scientific effort to understand the biology of SARS-CoV-2 has resulted in daunting numbers of genomic sequences. We witnessed evolutionary events that could mostly be inferred indirectly before, such as the emergence of variants with distinct phenotypes, for example transmissibility, severity and immune evasion. This Review explores the mechanisms that generate genetic variation in SARS-CoV-2, underlying the within-host and population-level processes that underpin these events. We examine the selective forces that likely drove the evolution of higher transmissibility and, in some cases, higher severity during the first year of the pandemic and the role of antigenic evolution during the second and third years, together with the implications of immune escape and reinfections, and the increasing evidence for and potential relevance of recombination. In order to understand how major lineages, such as variants of concern (VOCs), are generated, we contrast the evidence for the chronic infection model underlying the emergence of VOCs with the possibility of an animal reservoir playing a role in SARS-CoV-2 evolution, and conclude that the Nature Reviews Microbiology Review articlevirus (HIV; ~10 -4 × 10 -6 mutations per nucleotide per replication cycle), which, unlike coronaviruses, lack a 3′ exonuclease proofreading mechanism in their replication machinery 8,[10][11][12] . Insertions and deletions result from replication errors and can also generate diversity, such as the deletion at position 69-70 of the spike gene responsible for the S-gene dropout that was instrumental in detecting the SARS-CoV-2 Alpha variant, and has been reported to be associated with increased infectivity 13 .In addition to RNA replication errors, host-mediated genome editing by innate cell defence mechanisms may introduce substantial numbers of directed mutations into the SARS-CoV-2 genome, and thus may influence its evolutionary rate. Cellular mutational drivers include members of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family [14][15][16] , including APOBEC1, APOBEC3A and APOBEC3G that demonstrate editing activity for numerous DNA and RNA virus and retroviral genomes 17,18 , including SARS- . APOBEC activity has been inferred bioinformatically through observations of a substantial excess of C → U transitions over all other mutations 18,20,21 . SARS-CoV-2 genomes may also be edited by different cellular antiviral proteins (adenosine deaminases that act on RNA 1 (ADAR1)), leading to A → G mutations (and U → C mutations in opposite genomic strands) 21,22 .The potential editing-associated C → U mutations in the SARS-CoV-2 genome sequences introduce complexities to SARS-CoV-2 evolutionary genomic analysis. C → U mutations account, in part, for the strikingly high ratio of non-synonymous changes in SARS-CoV-2 genomes compared with those at synonymous sites; the mean dN/dS ratio ...

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

“…SARS-CoV-2 continues to cause disproportionate morbidity and mortality in older adults (1). Although vaccines effectively reduce this burden, immunity wanes in the months following vaccination (2,3) and the virus continues to evolve to escape population immunity (4,5). As newer versions of vaccines are adapted to recent SARS-CoV-2 variants (i.e., bivalent vaccine) (6), we must continue to determine how effective these vaccines are over time and against emerging variants and especially in vulnerable populations.…”

Immunogenicity of coronavirus disease 2019 vaccines in children: A review with ChatGPT

“…VOCs poses a challenge to the protection conferred by the COVID‐19 vaccines that received early approval for use, as VOCs contain mutations that may cause immune escape (Figure 4). 38 Subsequently, mRNA vaccines were shown to elicit robust antibody responses against many SARS‐CoV‐2 VOCs in children and adolescents. A study that assessed the VOC‐specific humoral responses including binding titers of several immunoglobulin isotypes and FcγR‐binding after two doses of BNT162b2 found children and adolescents maintained binding IgA and IgG against all four pre‐Omicron VOCs tested (Alpha, Beta, Gamma, and Delta) 62 .…”

“…Immune responses against variants of concern (VOCs), some of which can be prone to vaccine escape, are described (Figure 4). 38 As almost all children have or soon will be infected with SARS‐CoV‐2, we present evidence available for hybrid immunity, which is the synergistic immune response between infection and vaccination 39 . The information from this review aims to be useful for public health policymaking, promoting safe school environment, and ensuring children's best future outcomes for living with COVID‐19 long term, 40,41 now that the WHO has declared COVID‐19 no longer a public health emergency of international concern 42…”

Traceability of SARS‐CoV‐2 transmission through quasispecies analysis

“…Analysis of quasispecies data already provided valuable information for managing molecular contact tracing for other RNA viruses as human immunodeficiency virus (HIV) and human hepatitis C virus (HCV) 14 which, unlike coronaviruses, lack a 3′ exonuclease proofreading mechanism in their replication machinery 15 . However, it is well documented how different mechanisms may introduce mutations into the SARS‐CoV‐2 genome 16 . In addition to RNA replication errors, the generation of genetic diversity may be the result of multiple, viral and host‐mediated events involving genome size, replication mechanisms, postreplicative repair, spontaneous amino acid variation, environmental changes, and host‐mediated genome editing 17 .…”

“…15 However, it is well documented how different mechanisms may introduce mutations into the SARS-CoV-2 genome. 16 In addition to RNA replication errors, the generation of genetic diversity may be the result of multiple, viral and hostmediated events involving genome size, replication mechanisms, postreplicative repair, spontaneous amino acid variation, environmental changes, and host-mediated genome editing. 17 Several studies have shown that intrahost genomic variation is a common trait of SARS-CoV-2 infection.…”