Covid-19 Mutations and Variants

• Mutations are genetic variations in viruses that occur naturally over time.
• As the number of infected hosts grows, the likelihood that a virus will experience a mutation increases.
  • Not all mutations benefit the virus, but some mutations can significantly change the way the virus interacts with a host.
• Over time, enough mutations in key regions of the virus’s genetic code can cause an altered version of the original virus to spread. These different variations of the original virus are called variants.
• Over the course of the Covid-19 pandemic, multiple variants of the virus that causes Covid-19 have been documented.
  • These variants must be monitored closely to determine how sick people can become if infected, and how the changes to the virus could affect the way it spreads.
    • Some variations could make the virus more infectious or more resistant to vaccines.
  • Of the four main variations of SARS-CoV-2 that circulate the United States, the current dominant form is called the Delta
    • The Delta variant makes up approximately 92% of all positive Covid-19 cases that come through our lab. The Delta variant is here.
    • The Delta variant has kept some of the mutations found in other strains, while also developing new mutations that enable it to replicate and spread faster.

 

Delta Variant Differences

• Delta is reported to be almost twice as transmissible as the original strain. Significantly more viral particles exist in the respiratory tract of individuals infected with the Delta strain as compared to the reference virus.
  • Delta variant viral loads are reported to be ~1000 times higher than other SARS-CoV-2 variant infections, which means that individuals infected with Delta are more likely to spread the virus when they speak, cough, or sneeze.
  • The World Health Organization has named the Delta variant “the fastest and fittest” variant seen to date.
• The time after exposure until viral load reaches detectable levels is much shorter in the Delta variant. Incubation time was reported to be around 4 days long, compared to SARS-CoV-2’s ~8 days. This means that those infected with the Delta strain can spread the disease faster than usual.
• The symptoms associated with the Delta variant are different compared to the reference strain.
  • Fever, headache, runny nose, and sore throat are common, but cough and loss of smell are not associated with Delta.
  • Hearing impairment, gastrointestinal distress and blood clots can also occur.
• There is not enough data to draw conclusions regarding whether the Delta variant is linked to either higher rates of hospitalization or death compared to the reference virus.
  • Early studies have reported that hospitalization is twice as likely in unvaccinated individuals with the Delta variant than in unvaccinated individuals with the Alpha variant.
  • It is unknown whether Delta is making people sicker compared to the reference virus or if the surge of Delta in unprotected populations is to blame for the spike in hospitalizations.
    • Overall Covid-19 cases are again on the rise, hitting populations with lower vaccination rates especially hard. It is possible that where case numbers are high and vaccination percentages are low, hospital systems may be impacted by the increased workload, and case outcomes could be influenced as a result.
  • Although perhaps not more likely to cause death than the reference virus, the Delta variant can infect many more people, which means it has the potential to cause more death compared to the reference virus. This is a significant cause of concern.

 

Sites of Mutation

• Delta contains multiple mutations. Among others, there are three different mutations at the receptor-binding domain (RBD) of the spike protein, a mutation near the furin cleavage site, and several mutations located in an antigenic supersite at the spike protein N-terminal.
  • Substitution mutations at positions 417, 452 and 478 at the RBD are associated with conformational spike protein changes, increased binding affinity for ACE2 receptors, and increased electrostatic potential and steric hindrance, respectively.
  • A substitution mutation at position 681 near the furin cleavage site is associated with more efficient furin cleavage, meaning that more spike proteins are primed to invade host cells.
  • A part of the spike protein, located at the N-terminal, is known to be particularly susceptible to recognition and attack by antibodies. This is called an NTD-antigenic supersite. Multiple substitution and deletion mutations in an NTD-antigenic supersite have been reported to increase SARS-CoV-2 Delta’s ability to evade immune response.

 

 

• The SARS-CoV-2 spike protein is the focus of most commercially available vaccines. If mutations occur that alter how antibodies recognize or interact with the spike protein, it’s possible that vaccinations against the reference virus may be less effective against Delta. More data is needed to draw concrete conclusions.

 

Delta & Vulnerable Populations

• In the United States, most hospitalizations and deaths associated with Covid-19 are occurring in unvaccinated people.
  • CDC director Rochelle Walensky has stated that the pandemic is “becoming a pandemic of the unvaccinated”
• While there is little evidence to suggest that Delta targets children more than the reference virus, pediatric hospitals and ICUs are seeing an increase in cases, especially in less vaccinated areas.
  • Children under 12 years old are currently unable to get the Covid-19 vaccine, so they must instead rely on those around them becoming vaccinated for protection. In areas where vaccination rates are low, this already susceptible demographic becomes even more vulnerable.
• Although current vaccine efficiency against Delta is still being studied, as it stands, it’s reported to be “mostly effective” against the Delta variant. Booster doses are being considered to account for the arrival of new strains like the Delta variant.
• Each person that gets infected is another chance for SARS-CoV-2 to undergo mutations. The key to limiting the creation of new (potentially more dangerous) variants is to curb and control the rise of new Covid-19 cases.

 

Author: Elijah Bouldin