COVID-19: How, What, When, and WherePage 12 of 14

10. COVID-19 Variants

More than a year after the coronavirus pandemic began its assault on the world, we fear not only the spread of COVID-19, but also its new forms, or variants. Viruses are constantly changing, and this includes SARS-CoV-2, the virus that causes COVID-19. These genetic mutations occur over time and can lead to the emergence of new variants that may have different characteristics than the original virus.

A drawing of trees illustrating how one tree can incorporate characteristics from a nearby tree (variants). CDC. If you think about a virus like a tree growing and branching out; each branch on the tree is slightly different than the others. By comparing the branches, scientists can label them according to the differences. These small differences, or variants, have been studied and identified since the beginning of the pandemic.

Multiple variants of the virus that causes COVID-19 have been documented in the United States and globally during this pandemic. Sometimes new variants emerge and disappear. Other times, variants emerge and persist (CDCx, 2021a).

Although most mutations have little to no effect on the virus, in a large population of infected people—as in the current pandemic— “the odds are that some mutations will end up giving the virus an evolutionary edge, one that benefits SARS-COV-2 at great cost to us” (Forbes, 2021a).

A highly infectious variant has recently emerged. Called the Delta variant, it is currently the predominant strain of the virus in the United States. The Delta variant causes more infections and spreads faster than early forms of SARS-CoV-2. It nearly twice as contagious than earlier strains and may cause more severe illness than previous strains in unvaccinated persons. Fully vaccinated people with Delta variant breakthrough infections can spread the virus to others. However, vaccinated people appear to be infectious for a shorter period.

A graphic showing that the Delta variant is more contagious than the original COVID-19 strain. CDC.

Test Your Knowledge

Mutations in the COVID-19 virus:

  1. Rarely occur.
  2. Have only been seen in Britain.
  3. Occur over time and can lead to the emergence of new variants.
  4. Have not yet been seen in the United States.

Answer: C

If a viral mutation makes it more difficult for a virus to spread, it will eventually die out. If a mutation makes it easier for the virus to spread, it will have an advantage over existing strains and will likely become the dominant one (Kaplan, 2021).

Mutations, Variants and Strains

Mutations are changes in the genetic code of a virus that naturally occur over time when a virus makes copies of itself in an infected animal or person. These changes continue to occur as long as the virus spreads through populations. “What we are going to see is a cat-and-mouse game between the virus changing and the vaccine manufacturers having to quickly change their vaccines,” said Devi Sridhar, professor of global public health at the University of Edinburgh (NBC News, 2021).

The terms variant and strain are often used interchangeably, but they have different meanings. If a coronavirus specimen contains one or more mutations that another specimen lacks, but there is no detectable functional difference, it is called a variant. Many mutations do not affect the virus’s ability to spread or cause disease because they do not alter the major proteins involved in infection. However, eventually these are outmatched by variants with mutations that are more beneficial for the virus (CDCx, 2021b). If the mutations in a particular variant make the virus “demonstrably different”—more lethal, more able to evade a vaccine or easier to transmit—then it is a distinct strain (Kaplan, 2021).

Test Your Knowledge

A strain is:

  1. The same thing as a variant.
  2. The same as a mutation.
  3. A virus that has mutations but no functional difference from the original virus.
  4. A variant that has developed mutations than that make it “demonstrably different” from the original virus.

Answer: D

Genetic Sequencing

Genes in the SARS-CoV-2 genome that contain instructions to build parts of the virus are shown in different colors. For example, the brown section in the picture has genetic instructions to build the Spike protein, which then allows the virus to attach to human cells during infection. This section of the genome serves as a key region for monitoring mutations (CDCx, 2021b).

Illustration: SARS-CoV2 Genome

Genes in the SARS-CoV-2 genome that contain instructions to build parts of the virus are shown in different colors. For example, the brown section in the picture has genetic instructions to build the Spike protein, which then allows the virus to attach to human cells during infection. This section of the genome serves as a key region for monitoring mutations (CDCx, 2021b).

The SARS-CoV-2 genome encodes instructions organized into sections, called genes, to build the virus. A process called genomic sequencing is used to decode the genes and learn more about the virus. Genomic sequencing allows scientists to identify SARS-CoV-2 and monitor how it changes over time into new variants, understand how these changes affect the characteristics of the virus, and use this information to predict how it might impact health (CDCx, 2021b).

Potential Consequences of Emerging Variants

Some potential consequences of emerging variants are the following (CDCx,2021c):

  • Ability to spread more quickly in people. There is already evidence that some of the variants spread faster than the original COVID-19 virus.
  • Ability to cause either milder or more severe disease in people. In January 2021, experts in the UK reported that the B.1.1.7 variant may be associated with an increased risk of death compared to other variants. More studies are needed to confirm this finding.
  • Ability to evade detection by specific viral diagnostic tests. Most commercial reverse-transcription polymerase chain reaction (RT-PCR)–based tests have multiple targets to detect the virus, so that even if a mutation impacts one of the targets, the other RT-PCR targets will still work.
  • Decreased susceptibility to therapeutic agents such as monoclonal antibodies.
  • Ability to evade natural or vaccine-induced immunity. Both vaccination against and natural infection with SARS-CoV-2 produce a polyclonal response that targets several parts of the spike protein. The virus would likely need to accumulate multiple mutations in the spike protein to evade immunity induced by vaccines or by natural infection.

Among these possibilities, the last—the ability to evade vaccine-induced immunity—is the most concerning. Once a large proportion of the population is vaccinated, there will be immune pressure to favor and accelerate emergence of “escape mutants” with the ability to avoid vaccine antibodies. There is no evidence that this is occurring, and most experts believe escape mutants are unlikely to emerge because of the nature of the virus (CDCx, 2021c).

Test Your Knowledge

The most concerning consequence of emerging variants is:

  1. The ability to evade vaccine-induced immunity.
  2. Decreased susceptibility to therapeutic agents.
  3. Ability to evade detection by viral diagnostic tests.
  4. The ability to spread more quickly in people.

Answer: A

COVID-19 Variants

Coronaviruses are named for the crown-like spikes on their surfaces. Changes in the virus, including changes to its spikes, can affect how it spreads and what happens to people who are infected with it (CDCx, 2021a).

Multiple variants of the virus that causes COVID-19 are circulating globally. Currently, The B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and P.1 (Gamma) variants circulating in the United States are classified as variants of concern.

Coronavirus Genome

Illustration: Coronavirus Envelope Showing Spike Proteins

The virus genome is packed inside an envelope that contains proteins, including the Spike protein. Source: CDCx.

  1. The United Kingdom (UK) identified a variant called B.1.1.7, (now called the Alpha variant) with a large number of mutations, in the fall of 2020. This variant spread more easily and quickly than other variants and within 3 months, it was the dominant strain in Britain. It is up to 75% more contagious and has a higher viral load than previous strains. Today, its prevalence in Britain is estimated to be above 90% (Forbes, 2021b).

    In January 2021, experts in the UK reported that the Alpha variant may be associated with an increased risk of death compared to other variant viruses, but more studies are needed to confirm this finding. The UK variant has since been detected in many countries around the world and was first detected in the United States at the end of December 2020 (CDCx, 2021a).

    Scientists say this variant will become the dominant one in the United States by the end of March 2021 (NY Times, 2021).

Illustration: Transformation of SARS-CoV-2 Into New Variant of Concern

New Variant of Concern 202012/01 of novel SARS-COV-2 have emerged as a new mutation, with high transmissibility raising greater concern in the existing pandemic. Image Credit: Created with BioRender.com. CC-BY-SA-4.0.

  1. In South Africa, another variant called B.1.351 (now called the Beta variant) emerged independently of B.1.1.7 (Alpha variant). Originally detected in early October 2020, Beta variant shares some mutations with the Alpha variant. Cases caused by this variant have been reported in the United States since the end of January 2021 (CDCx, 2021a).

    This variant has a mutation that seems to make it more contagious: N501Y. Another mutation called E484K may help the virus get past a person’s immune system. Spike proteins on coronaviruses allow them to gain entry into human cells, and some of the mutations seen in the South African variant are on the spike proteins where existing vaccines are designed to work. There are concerns that this variant can gain easier access to host cells and vaccines may not work as well against it (BBC News, 2021).
  1. In Brazil, a variant called P.1 (now called the Gamma variant) emerged that was first identified in travelers from Brazil, who were tested during routine screening at an airport in Japan in early January. This variant has 17 unique mutations, including 3 in the receptor binding domain of the spike protein that may affect its ability to be recognized by antibodies. It was first detected in the United States at the end of January 2021 (CDCx, 2021a).

One specific mutation, called D614G, is shared by these three variants. It gives the variants the ability to spread more quickly than the predominant viruses. There also is epidemiologic evidence that variants with this specific mutation spread more quickly than viruses without the mutation (CDCx, 2021d).

Variants of Interest

California Variant

The California variant, referred to as B.1.427/B.1.429, is thought to have caused the surge of COVID-19 cases seen in Southern California in early 2021. This variant was not found in any samples taken in September 2020 by researchers at the University of California, San Francisco, but by the end of January it was in more than half their samples (US News and World Reports, 2021).

“This variant is concerning because our data shows that it is more contagious, more likely to be associated with severe illness, and at least partially resistant to neutralizing antibodies,” said study author Charles Chiu, an infectious diseases physician and sequencing expert at UCSF (US News and World Reports, 2021).

New York Variant

The New York variant appeared in New York in late November 2020. Caltech researchers discovered the variant in about a quarter of 1200 viral samples studied in New York in February 2021. Columbia University researchers found the variant in 12% of their samples from the second week of February 2021. They found that those infected with the New York variant were more likely to be older and to have been hospitalized than patients infected with the original virus (AP, 2021).

Both Caltech and Columbia researchers found that this variant has the same mutation seen in other variants of concern that could potentially lessen the effectiveness of existing vaccines (AP, 2021).

Variants Can Be Minimized

“Viruses are constantly mutating—or making “typos” in their genetic code—as they spread and make copies of themselves” (AP, 2021). Most of the mutations are not concerning and some may even weaken a virus; however, some mutations make a virus more contagious, deadlier, and/or able to get around vaccine antibodies. Genetic sequencing is used to identify the worrisome variants that may need new treatments and vaccines.

As long as this virus continues to spread, there will be mutations, new variants and strains. Limiting the spread of COVID-19 through measures such as social distancing, mask wearing, and vaccinations gives it less opportunity to mutate and gives us time to get ahead of the virus.