Variant evolution_old
Since COVID-19 first spread around the world in 2020, several variants have evolved. Most of these variants were common for a relatively short period of time and have since become extinct due to being outcompeted by other variants. In this section, we will discuss the evolution of Delta and Omicron, two of the most dominant variants we have observed throughout the pandemic.
Delta variant
The Delta variant was first reported in late 2020 and became widespread by spring 2021. This variant differed from previous variants in its ability to spread through the population quickly, infecting people who had been previously infected by other strains or had been fully vaccinated, and inflicting some of the most serious symptoms. Mutations on the gene coding for the spike protein allowed this variant to go undetected by many of the antibodies a host may have produced from a previous infection or vaccine. The rise of this variant is an example of a host-pathogen arms race, where the pathogen evolves in response to the defense mechanisms of the host.
Host-pathogen arms race
As hosts in human populations are exposed to a particular pathogen, the adaptive immune system begins to produce antibodies that provide long-term immunity to that particular virus. As a result, viruses that harbor mutations that give them a slight edge against the host’s adaptive immunity replicate in greater numbers compared to viruses that don’t have these mutations, ultimately leading to the emergence of new variants (i.e. natural selection!). As these new variants emerge, hosts in the population gain immunity to these new variants, and process repeats itself – sometimes indefinitely (hence, the name “arms race”). This process is why the general consensus is that SARS-CoV-2 is here to stay, and also why vaccines for other viruses such as influenza are updated every year.
In the case of the Delta variant, the 10 mutations on the spike gene represent 10 portions of the genome that differs from the original strain of SARS-CoV-2. Of these 10 mutations, many of them have been implicated in helping the virus evade immunity acquired via both previous natural infection and vaccination. One specific mutation that is well understood is the L452R mutation. This means that the 452nd amino acid in the spike protein has been changed from a arginine (R) from a leucine (L). A closer analysis reveals that this is the result of a single nucleotide substitution of a uracil to a guanine. Researchers have uncovered that this single change slightly changes the shape of the receptor binding domain on the spike protein – the portion of the spike protein that binds to the ACE2 receptor on the surface of human cells. Not only does this mutation appear increase the binding affinity to the ACE2 receptor, but it also allows viruses with this mutation to evade antibodies that were designed to target the receptor binding domain of previous strains of the virus. Such an advantage can contribute to explain the rapid spread of Delta throughout 2021.
Omicron variant
The Omicron variant was first reported in November 2021, near the peak of Delta variant infections. Omicron was quickly identified as a variant of concern by the World Health Organization due to 37 novel mutations in the gene coding for the spike protein. These mutations resulted in increased transmissibility and have allowed the virus to evade adaptive immune responses. As a result, people who had been previously infected with another variant or had been fully vaccinated were infected by Omicron at higher rates than previous variants.
Evolutionary trade-offs
Airborne respiratory viruses with fast reproduction rates sometimes evolve traits that simultaneously increases their transmissibility, but decreases their virulence (i.e. a trade-off). However, these trade-offs can be maintained when the reproductive benefit of being more transmissible outweighs the cost of being less virulent. In the case of Omicron, the tendency to infect upper airway tissues instead of the lungs is a clear example of a transmissibility-virulence trade-off. The virulence of this variant is lower because it is no longer infecting vital organ tissues in the same way, but its transmisibility is higher because more replication occurs in the upper airways where it can readily spread. There are a couple of mechanisms that underlie this trade-off: The way the virus enters the cell, and the way it interacts with the immune system.
One of the main differences between Omicron and Delta variants is the way in which they enter the cell. The delta variant, along with the original variant of SARS-CoV-2, enters the cell via viral fusion. This process requires the help of the transmembrane enzyme TMPRSS2. On the other hand, Omicron enters the cell via endocytosis, a process that can occur in the absence of TMPRSS2 enzymes. TMPRSS2 enzymes are much more abundant in lung tissue. This means that the Delta variant dove deep into the respiratory tract in order to successfully replicate, while the Omicron variant can successfully replicate in upper airway tissues, even in the absence of TMPRSS2.
Another difference between the Omicron and Delta variants are the ways in which our immune system responds to infection. The Delta variant is effective in evading interferons, proteins that alert white blood cells of potential threats. As a result, these viruses replicate for a relatively long period of time before the host’s adaptive immune response is activated. This extra time allows for several rounds of viral replication before a strong immune response, and therefore a higher viral load. Higher levels of the virus make the host more likely to suffer from severe disease, making Delta more virulent than previous strains.
Conversely, the Omicron variant triggers interferons quickly, resulting in a swift immune response. As a result, Omicron does not infect the lungs as effectively as Delta, since interferon expression is especially high in vital organ tissues. Due to the rapid response, the host sneezes more relative to people infected with Delta. This sneezing effectively increases the transmissibility of the virus, even though the viral load is typically much lower than hosts with Delta or other variants. Additionally, since the adaptive immune response is quickly activated, symptoms are typically more similar to the common cold and less similar to other variants. As a result, people often are unaware that they are infected and will not take the same distancing precautions they would if they were experiencing more severe symptoms. These evolutionary tradeoffs have resulted in Omicron being more transmissible than any other strain, while symptoms are generally less severe than other strains.