- Virology
- Genomic Epidemiology of SARS-CoV-2
- Nextstrain August 2020 Update of COVID-19 Genomic Epidemiology
- SARS-CoV-2 Lineages
- GISAID hCoV-19 Spike Glycoprotein Mutation Surveillance Dashboard
- Genomic Epidemiology of Superspreading Events in Austria
- WHO Guide to the Genomic Sequencing of SARS-CoV-2
- See Clinically Relevant Mutations Below.
- Molecular Virology
- Video Lecture: Molecular Virology of Coronaviruses
- Lu M, et al. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles. Cell Host Microbe. Dec 2020. (Accompanying Commentary)
- Greaney AJ, et al. Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host Microbe. Nov 2020.
- Turoňová B, et al. In Situ Structural Analysis of SARS-CoV-2 Spike Reveals Flexibility Mediated by Three Hinges. Science. Oct 2020.
- Finkel Y, et al. The Coding Capacity of SARS-CoV-2. Nature. Sep 2020.
- Ke Z, et al. Structures and Distributions of SARS-CoV-2 Spike Proteins on Intact Virions. Nature. Aug 2020.
- Starr TN, et al. Prospective Mapping of Viral Mutations That Escape Antibodies Used to Treat COVID-19. Dec 2020. (Not Peer Reviewed)
- Clinically Relevant Mutations in the SARS-CoV-2 Genome
- Notable SARS-CoV-2 Mutations and Variants (Table Summary / Spike Mutations Diagram)
- Summary: Lauring AS, et al. Genetic Variants of SARS-CoV-2—What Do They Mean? JAMA. Jan 2021.
- Yang H-C, et al. Analysis of Genomic Distributions of SARS-CoV-2 Reveals a Dominant Strain Type with Strong Allelic Associations. Proc Natl Acad Sci USA. Nov 2020.
- Greaney AJ, et al. Comprehensive Mapping of Mutations to the SARS-CoV-2 Receptor-Binding Domain That Affect Recognition by Polyclonal Human Serum Antibodies. Jan 2021. (Author Summary / Not Peer Reviewed)
- G614 Dominant Strain: Korber B, et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell. July 2020.
- ORFΔ3b Mutation: Lam et al. Loss of ORF3b in the Circulating SARS-CoV-2 Strains. Emerg Microbes Infect. Nov 2020.
- Globally circulating mutation that lack a full-length form of orf3b (known as orfΔ3b). Approximately 24% of circulating sequences carry orfΔ3b. Emergence of this variants coincides with the emergence of the G614 variant. SARS-CoV-2 orfΔ3b does not block interferon production, unlike full-length orf3b. Thus, these Δ3b variants have lost the ability to block the antiviral activity of interferons, but the effect of this on virulence has yet to be determined.
- 501Y.V1, 501Y.V2, and 501Y.V3 Circulating Variants: Tegally et al. Emergence and Rapid Spread of a New Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Lineage with Multiple Spike Mutations in South Africa. Dec 2020. (Not Peer Reviewed)
- E484K Mutation: Comprehensive Mapping of Mutations to the SARS-CoV-2 Receptor-Binding Domain That Affect Recognition by Polyclonal Human Serum Antibodies. Jan 2021. (Not Peer Reviewed)
- L452R Circulating Variant:
- This variant is characterized by the L452R mutation (leucine [L] to arginine [R] at position 452 of the spike protein receptor binding domain) and accounts for a rapidly increasing proportion of infections in California. From late November to early January, the L452R circulating variant increased in prevalence from 3.8% to 25.2% of sequenced samples. This variant has been found in several high attack rate outbreaks in Santa Clara County, however a causal relationship between this mutation and any phenotypic changes, including increased transmissibility, has yet to be established (see California DPH release). Given that this clade was found at low frequency from September through October before rapidly expanding in November, it is highly possible that its observed prevalence is due it being spread by the current surge in cases rather than causing it. The L452R mutation, along with accompanying S13I and W152C mutations, was initially detected in Alameda County, California in early May, but was first identified in mid-March in Denmark. This mutation has been occasionally observed worldwide but is now predominantly found in California.
- N439K Circulating Variant: Thomson et al. The Circulating SARS-CoV-2 Spike Variant N439K Maintains Fitness While Evading Antibody-Mediated Immunity. Nov 2020. (Not Peer Reviewed)
- Δ382 Extinct Variant:Young et al. Effects of a Major Deletion in the SARS-CoV-2 Genome on the Severity of Infection and the Inflammatory Response: An Observational Cohort Study. Lancet. Aug 2020. (Well Written Explanation)
- Less severe, now extinct, “Δ382” variant that began spreading in East Asia in Jan-Feb 2020. This variant has a 382-nucleotide deletion in gene regions that in-part code for proteins ORF7B and ORF8 (which helps protect the virus from T cells), thus the “∆382” variant.
- Additional Variants and Mutations of Interest: CoVariants: SARS-CoV-2 Mutations and Variants of Interest (Table Summary – Dec 2020)
- For more information on the emergence and spread of SARS-CoV-2 in the U.S. and Europe, see Worobey et al. and Bedford et al.
- Antigenic Drift
- More virulent (see Hou et al.), now globally dominant, “G614” strain that began spreading in Europe and the U.S. East Coast in February-March 2020 (see Korber et al.). This mutation is a change of the amino acid at position 614, from aspartic acid (D) to glycine (G), thus the “D614G” mutation. The D614G mutation marks the evolution of the initial “D614” (Wuhan) strain to the more prevalent “G614” or “614G” strain. Human neutralizing antibodies cross-react to both strains (see Klumpp-Thomas et al.). For more background on the G614 strain, see Baric. For more evidence on the phenotypic traits and fitness of the G614 strain see van Dorp et al., Volz et al., Zhou et al. (not peer reviewed), and Plante et al. For discussion of its role in second wave infections see Long et al. For a summary of some of these papers and others on the G614 strain, see Nature News as well as this well written explanation.
- In late 2020 and early 2021, three new prevalent circulating variants with 614G backgrounds were identified, N501Y.1 (lineage B.1.1.7) in the UK and Europe, 501Y.V2 (lineage B.1.351) in South Africa, and 501Y.V3 (lineage P.1) in Brazil and Japan (see O’Toole et al.). All variants share the same mutation, N501Y (asparagine [N] to tyrosine [Y] at position 501), of the spike protein receptor binding domain. However, these variants arose independently and are genetically distinct. The N501Y mutation appears to increase transmissibility via increasing ACE2 receptor binding affinity (See Starr et al. and Gu et al.). The N501Y mutation alone is not believed to result in vaccine (see Xie et al. [not peer reviewed] and Gu et al.) or neutralizing antibody (see Haynes et al.) resistance, however the multiple mutations within each of these variants do appear to cause a modest reduction in mRNA vaccine efficacy—see each variant below for more info.
[Note on Lineages: B is the original Chinese lineage, B.1 is the lineage that seeded the Italian outbreak, B.1.1 a European lineage derived from that, and B.1.1.7 is the rapidly expanding UK lineage including the 501Y.V1 variant. Due to phenotypic changes associated with these 501Y variants, they may soon be considered strains.]
501Y.V1 variant (B.1.1.7 lineage) accounts for a rapidly increasing proportion of infections in the UK, Europe, and parts of the U.S. and has an unusually large number of genetic changes, particularly in the spike protein (see Rambaut et al. [not peer reviewed]). This variant is estimated to have emerged in September 2020 and has quickly become the dominant circulating variant in England (see Public Health England Reports). Preliminary analysis in the UK suggests that this variant is significantly more transmissible than previously circulating variants, with an estimated potential to increase the reproductive number (R) by 0.4 or greater with an estimated increased transmissibility of ~56% (see Davies et al., Volz et al., and Vöhringer et al. [not peer reviewed]), with no observed increase in virulence (see the MRC GIDA Report, ECDC Threat Assessment, and CDC FAQ), and a possible substantial increase in viral load (see Golubchik et al. and Kidd et al.). Antibody immunoevasion has not been observed with 501Y.V1 (see Haynes et al.), however preliminary data from 15 subjects suggests that the mutations in the 501Y.V1 variant result in a modest reduction (fold change > 3) in efficacy of the Pfizer (tozinameran) vaccine (Max Reduction: 6x; Median Reduction: 3.85x). 501Y.V1 has likely been circulating in the U.S. since mid-November (see Larsen et al.) and is expected to become the predominant variant in the U.S. in March (see Galloway et al.). For known 501Y.V1 cases in the U.S. see CDC: US Cases Caused by Variants.
501Y.V2 variant (B.1.351 lineage) has mainly thus far been observed in South Africa and Brazil and has a distinct set of genetic changes characterized by N501Y, E484K (see below), and K417N mutations in the spike protein (see KRISP Briefing). The combination of significantly increased transmissibility from the N501Y mutation and the immunoevasive effects of the E484K mutation, make this a particularly concerning variant (see Pearson et al. [not peer reviewed]). Preliminary data from South Africa’s NICD showed that in convalescent sera from 44 subjects infected during the first wave, >90% showed showed reduced immunity and 48% had complete immune escape to 501Y.V2.
501Y.V3 variant (P.1 lineage, a descendent of the B.1.1.28 lineage) has mainly been found circulating in Manaus, north Brazil, and is characterized by N501Y, E484K (see below), and K417T mutations in the spike protein (see Faria et al. [not peer reviewed]). As with 501Y.V2, the combination of the N501Y mutation and immunoevasive E484K mutation, make this a particularly concerning variant.
- Immunoevasive E484K mutation (glutamic acid [E] to lysine [K] at position 484) of the spike protein receptor binding domain. This mutation impacts binding and neutralization by polyclonal serum antibodies targeting the receptor binding domain causing neutralization by some sera to be reduced by greater than 10-fold (see Weisblum et al.; Greaney et al., Andreano et al., Liu et al., and Naveca et al. [latter not peer reviewed]). This mutation has been found in viral lineages in South Africa, Brazil, and Japan, namely B.1.351 (501Y.V2), P.1 (501Y.V3), and B.1.1.248 (a descendent of B.1.1.28) (see Nonka et al., Voloch et al., and Faria et al. [all not peer reviewed]).
For information on the associated ΔH69/V70 mutation, which is also found in the below N439K variant and throughout the U.S. and may play a role in increased transmissibility, see Kemp et al., Kemp et al., and Larsen et al. (not peer reviewed)]. For context on the potential significance of the associated P681H mutation—located immediately adjacent to the furin cleavage site, a known location of biological significance—see Hoffmann et al.
- Immunoevasive N439K mutation (asparagine [N] to lysine [K] at position 439) of the spike protein receptor binding domain, which is a key target of antibodies against the virus. This variant has been observed to escape the activity of neutralizing antibodies, including those from convalescent sera and manufactured monoclonal antibodies in clinical trials. The N439K variant has emerged independently at least twice and now appears to be present in ~5% of infections in Europe. For more information on this and other immunoevasive variants (i.e. Zoonotic Y453F), see Greaney et al. and Starr et al. not peer reviewed).
- Note: Despite widespread incorrect media reports on the findings of Basavaraju et al., there remains virtually no evidence of SARS-CoV-2 widely circulating in the U.S. prior to January 19, 2020. Rather, these findings likely represent cross-reactivity with other endemic human coronaviruses. For more, see this explanation by Virologist Trevor Bedford.
- Zoonosis
- Minks
- Zhou P, et al. SARS-CoV-2 Spillover Events. Science. Jan 2021.
- Oude Munnink BB, et al. Transmission of SARS-CoV-2 on Mink Farms between Humans and Mink and Back to Humans. Science. Nov 2020.
- Hammer AS, et al. SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark. Emerg Infect Dis. Nov 2020.
- van Dorp L, et al. Recurrent Mutations in SARS-CoV-2 Genomes Isolated from Mink Point to Rapid Host-Adaptation. Nov 2020. (Not Peer Reviewed)
- Domesticated Pets
- Bosco-Lauth AM, et al. Experimental Infection of Domestic Dogs and Cats with SARS-CoV-2: Pathogenesis, Transmission, and Response to Reexposure in Cats. Proc Natl Acad Sci U S A. Oct 2020.
- Patterson EI, et al. Evidence of Exposure to SARS-CoV-2 in Cats and Dogs from Households in Italy. Nat Commun. Dec 2020.
- Origins of SARS-CoV-2
- SARS-CoV-2 is Not a Purposefully Manipulated Virus and it’s Lineage has been Circulating in Bats for Decades
Virology
Last Updated on 01/19/2021 @ 3:06 PM EST
