The Evolution of SARS-CoV-2
As the youngest of the coronavirus family, SARS-CoV-2 did his parents proud. Here's the evolution of the coronavirus that shook the world silly.
The Coronavirus Family
There are seven coronavirus species known to infect humans. These include countless variants (major mutations) and strains (minor mutations). They all share the same fundamental features:
Anatomy of the SARS-CoV-2 virus. The coronavirus is essentially a string of single-stranded RNA inside a capsid (protein shell). The capsid is surrounded by a lipid envelope studded with spikes.
Viruses are not cells. They're not even technically alive, since they lack critical functions like growth and metabolism. But they do replicate, mutate, and evolve by deviously hijacking our own biological equipment.
Most of us grew up with just three species of coronavirus—known as NL63, 229E, and OC43—which cause common colds, and occasionally a spot of pneumonia.
But since 2003, four new species have evolved. This gave us HKU1, MERS, SARS, and COVID-19. As we've seen in the news far too often, they cause mild to severe symptoms ranging from a head cold to respiratory failure.
Let's now place them in their family tree. Genetic analysis and molecular clock dating give us the estimated date of origin of all seven coronaviruses today.
The seven human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2) share common ancestors in bats, mice, and domestic animals.
We're all exposed to endemic coronaviruses in the first few years of life. Fortunately, our young immune system is amped to tackle these onslaughts, rapidly destroying viral invaders and tucking their profiles away into long term memory—aka the adaptive immune system.
But as we age, our immune system becomes less responsive. Viral infections take an increasing toll on the body, and some can remain hidden in our tissues for years.
"RNA [of 229E] is detected in about 44% (40 of 90) of human brains tested." - Human Coronavirus (2021)
So when a novel virus hits humanity, the elderly tend to take a double hit. Not only is the immune system degraded, but it has zero experience of the new pathogen.
How Does COVID Compare to Other Diseases?
The latest Omicron variant is almost as infectious as measles, while being deadlier than seasonal flu and swine flu.
The fatality and infection rates of COVID variant compared to other infectious diseases.
Due to such widespread infection, SARS-CoV-2 continues to evolve rapidly, which gives COVID an evolving disease profile.
When the pandemic began, the average infected person spread the disease to 2.7 other people. This is known as the Reproductive Number (R0). It has increased by 334% in two years.
- Wuhan variant R0 = 2.7
- Delta variant R0 = 5.1 (+89%)
- Omicron variant R0 = 12 (+135%)
At the same time, the Case Fatality Rate (CFR) has fallen, despite 40% of the global population remaining unvaccinated. It means COVID has evolved to become a milder disease.
- Wuhan variant CFR = 1.6%
- Delta variant CFR = 1.3% (-19%)
- Omicron variant CFR = 0.9% (-31%)
However, while Omicron is 31% less deadly than Delta, it's 135% more transmissible. Overall, this relatively milder variant has actually killed more people, bringing the confirmed death toll close to 1 million people in the US alone.
How Do Viral Variants Evolve?
The evolution of SARS-CoV-2 comes down to the spike protein: the biological key that allows the virus to gain entry to our cells.
The spike protein contains a critical cluster of amino acids known as the Receptor Binding Domain. When a spike makes contact with a cell receptor, the RBD oscillates, jiggling the key in the lock. The receptor binds to the virus and draws it into its membrane.
At the same time, the spike protein shapeshifts. The prefusion spike folds and breaks apart, taking on a new molecular configuration known as the postfusion state.
The shapeshifting spike protein. (1) In the prefusion state, the RBD oscillates to unlock ACE2 cell receptors. Likewise, the NTD can unlock AXL cell receptors. (2) Receptor binding sees the spike cleaved into its postfusion subunits: S1 subunits float free, while the S2 subunit remains anchored to the cell membrane.
But targeting a single antigen puts all our eggs in one basket. Whether we're infected or vaccinated against SARS-CoV-2, our antibodies are geared strongly toward the spike protein. This creates an evolutionary pressure on the virus to evolve different spikes.
And viruses evolve fast. Every time a virus replicates inside a cell, it has the opportunity to mutate. In fact, mutations are so common that we can trace the genetic signature and link individual cases to relatively small clusters of infections.
Mutations in SARS-CoV-2 have changed the structure of the spike protein to create antigenic drift.
How has antigenic drift played out with COVID?
- Delta has two mutations on the RBD. It binds better with cell receptors which accelerates viral replication. It also has an affinity for the lungs which are loaded with ACE2 receptors, creating more severe disease.
- Omicron has 15 mutations on the RBD. It can replicate almost 100x faster than Delta, which may be why it's content to stay in the upper respiratory tract. More viral particles in the upper airways increases transmission.
Comparing the spike mutations of the Omicron, Delta, and Alpha variants.
How Will The Pandemic End?
The proliferation of Omicron will ultimately give us better herd immunity against SARS-CoV-2. Indeed, the WHO predicts the acute phase of the COVID pandemic will end by mid-2022. This doesn't mean COVID will go away; endemicity simply means the end of exponential spread, with infection rates falling to a predictable background rate.
We're not out of the woods yet. And it's still possible that a deadlier SARS-CoV-2 variant will emerge. It's thought that Spanish Flu, which killed an estimated 50 million people, evolved to be deadlier before it decreased in pathogenicity. Other viruses, like Ebola, have become more pathogenic over time.
History suggests COVID will be with us for the rest of our lives. It's shaping up to be a highly infectious disease that's worse than flu and mutates year-on-year, necessitating annual vaccinations. In the meantime, scientists and politicians can only guess as to the best strategic moves as complex pandemic dynamics play out.
Some major drivers of pandemic dynamics.
Becky Casale is a science blogger based in Auckland. If you like her content, please share it with your friends. If you don't like it, why not punish your enemies by sharing it with them?
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