Have any mutations been discovered for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19)?

Updated: Jun 25, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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The full genome of SARS-CoV-2 was first posted by Chinese health authorities soon after the initial detection, facilitating viral characterization and diagnosis. The CDC analyzed the genome from the first US patient who developed the infection on January 24, 2020, concluding that the sequence is nearly identical to the sequences reported by China. [1]  SARS-CoV-2 is a group 2b beta-coronavirus that has at least 70% similarity in genetic sequence to SARS-CoV. [30] Like MERS-CoV and SARS-CoV, SARS-CoV-2 originated in bats. [1]  

A new virus variant emerges when the virus develops 1 or more mutations that differentiate it from the predominant virus variants circulating in a population. The CDC surveillance of SARS-CoV-2 variants includes US COVID-19 cases caused by variants. The site also includes which mutations are associated with particular variants. The CDC has launched a genomic surveillance dashboard and a website tracking US COVID-19 case trends caused by variants. Researchers are studying how variants may or may not alter the extent of protection by available vaccines. 

Mutations

Viral mutations may naturally occur anywhere in the SARS-CoV-2 genome. Unlike the human DNA genome, which is slow to mutate, RNA viruses can readily, and quickly, mutate. A mutation may alter the viral function (eg, enhance receptor binding), or may have no discernable function. 

Mutations have been identified for the receptor-binding domain (RBD) on the spike protein of SARS-CoV-2. Several of these mutations display higher binding affinity to human ACE2, likely owing to enhanced structural stabilization of the RBD. Whether a mutation enhances viral transmission is a question to explore. Possible mechanisms of increased transmissibility include increased viral shedding, longer contagious interval, increased infectivity, or increased environmental stability. 

Table 1. Examples of mutations and resulting actions (Open Table in a new window)

Mutation

Actions

Variants with Mutation

N501Y

Increased viral load

Alpha UK (B.1.117)

Del69-70

Increased ACE binding

Alpha UK (B.1.117)

E484K

Increased transmission and virulence; decreased neutralization by vaccines and monoclonal antibodies

When combined with other mutations, may result in an escape mutation

Beta South Africa (B.1.351), Gamma Brazil (P1), and Iota NYC (B.1.526 and B.1.526.1)

L452R

Monoclonal antibodies may be less effective

B.1.526.1, Epsilon California (B.1.427 and B.1.429), and Delta India (B.1.617 linages and sub-lineages)

D614G

Increased transmission

One of the first documented mutations in the United States after initially circulating in Europe. Included in nearly all variants of interest and variants of concern.

Variants of Concern in the United States

As mentioned, viruses such as SARS-CoV-2 change. Among the hundreds of variants detected in the first year of the pandemic, the ones that are most concerning are the so-called variants of concern (VOCs). Variants can affect efficacy of vaccines and antibody directed therapies. Researchers are studying how variants may or may not alter the extent of protection by available vaccines and antibody-directed therapies

United Kingdom VOC 

The CDC tracks variant proportions circulating in United States and estimates the B.1.1.7 variant (Alpha) which was first detected in the United Kingdom accounted for over 44% of cases from January 2 to March 27, 2021. On April 7, 2021, the CDC announced B.1.1.7 is the dominant strain circulating in the United States. In mid-June 2021, it remains the dominant strain with approximately 70% of new cases. 

A novel spike mutation with deletions of (delta)69/delta(70) has been shown to occur de novo on multiple occasions and be maintained through sustained transmission in association with other mutations. [79]  This is the source of intense scrutiny in Europe, especially in the United Kingdom. A recent VOC – 202012/01 (201/501Y.V1) contains the deletion 69-70 as well as several other mutations including: N501Y, A570D, D614G, P681H, T716I, S982A, D1118H. The variant is being investigated as a cause of rapid increase in case numbers possibly due to increased viral loads and transmissibility. The N501Y mutation seems to increase viral loads 0.5 log. [80]   

Additionally, VOC-202012/01 has mutations that appear to account for its enhanced transmission. The N501Y replacement on the spike protein has been shown to increase ACE2 binding and cell infectivity in animal models. The deletion at positions 69 and 70 of the spike protein (delta69-70) has been associated with diagnostic test failure for the ThermoFisher TaqPath probe targeting the spike protein. Therefore, British labs are using this test failure to identify the variant. [81]    

Surveillance data from the UK national community testing (“Pillar 2”) showed a rapid increase in S-gene target failures (SGTF) in PCR testing for SARS-CoV-2 in November and December 2020. The R0 of this variant seems higher. At the same time that the transmission of the wild type virus was dropping, the variant increased, suggesting that the same recommendations (eg, masks, social distancing) may not be enough. The UK variant is also infecting more children (aged 19 years and younger) than the wild type indicating that it may be more transmissible in children. This has raised concerns because a relative sparing of children has been observed to date. This variant is hypothesized to have a stronger ACE binding than the original variant, which was felt to have trouble infecting younger individuals as they express ACE to a lesser degree. [81]   

South African VOC (B.1.351 [Beta])

The E484K mutation was found initially in the South Africa and Brazil variants in late 2020, and was observed in the UK variant in early February 2021.

Position 484 and 501 mutations that are both present in the South African variant, and the combination is a concern that immune escape may occur. These mutations, among others, have combined to create the VOC B.1.351. The mutation at the 501 position changes the shape of the RBD by rotating it by 20 degrees to allow deeper binding. The mutation at the 484 position changes the RBD to a positive charge, and allows a higher affinity to the ACE2 receptor. [82]   

Brazilian VOCs (P.1 [Gamma])

Sabino et al describe resurgence of COVID-19 in Manaus, Brazil in January 2021, despite a high seroprevalence. A study of blood donors indicated that 76% of the population had been infected with SARS-CoV-2 by October 2020. Hospitalizations for COVID-19 in Manaus numbered 3,431 in January 1-19, 2021 compared with 552 for December 1-19, 2020. Hospitalizations had remained stable and low for 7 months prior to December. Several postulated variables regarding this resurgence include waning titers to the original viral lineage and the high prevalence of the P.1 variant, which was first discovered in Manaus. [83]  In addition, researchers are monitoring emergence of a second variant in Brazil, P.2, identified in Rio de Janeiro. As of April 15, the CDC lists P.2 as a variant of interest. 

California VOCs 

VOCs B.1.427 (Epsilon) and B.1.429 (Epsilon) emerged in California. These variants accounted for 2.9% and 6.9% of variants circulating in the United States between January 2 to March 27, 2021. An approximate 20% increase of transmission has been observed with this variant.

India VOC

The Delta variant (B.1.617.2) has shown a rapid increase of cases in India since early 2021. This variant increases ACE binding and transmissibility. An approximate 6.8-fold decreased neutralization for mRNA vaccines and convalescent plasma has also been observed with the Delta variant. [84, 85] As of mid-June 2021, the CDC estimates the Delta variant accounts for 10% of new cases in the United States. 

Variants of Interest in the United States

As variants emerge worldwide, the concern for vaccine efficacy remains a major focus. Owing to the rapid development of mutations and variants, the CDC is also tracking variants of interest that are not yet widely circulating in the United States.

Possible attributes include:

  • Specific genetic markers that are predicted to affect transmission, diagnostics, therapeutics, or immune escape
  • Evidence that it is the cause of an increased proportion of cases or unique outbreak clusters
  • Limited prevalence or expansion in the US or in other countries

Table 2. Examples of variants of interest in the United States (Open Table in a new window)

Variant of Interest

First Detected

B.1.525 (Eta)

United Kingdom/Nigeria - December 2020

B.1.526 (Iota)

United States (New York) - November 2020

B.1.526.1

United States (New York) - October 2020

B.1.617

India - February 2021

B.1.617.1 (Kappa)

India - December 2020

B.1.617.3

India - October 2020

P.2 (Zeta)

Brazil - April 2020

 


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