why-the-coronavirus’s-delta-variant-dominated-2021

2021 was a year of coronavirus variants. 

Alpha and beta kicked off the year, and several worrisome variants later, omicron is closing it out. How omicron may come to define the pandemic’s future remains uncertain. But even as omicron comes on strong, one variant, which rose to global dominance midyear in a way variants like alpha and beta never did, continues to largely define the pandemic right now: delta.

Things had actually seemed to be looking up in some parts of the world in the late spring and early summer of 2021, a year and a half into the COVID-19 pandemic. In the United States, for instance, millions of people were vaccinated, cases of the disease were falling, and people were beginning to socialize and resume normal activities. 

But then delta hit hard. First spotted in India in October 2020, this variant of SARS-CoV-2, the coronavirus that causes COVID-19, quickly swept around the world, supplanting other versions of the virus in 2021 (SN: 7/2/21). Delta overwhelmed health care systems, tore through unvaccinated populations and showed that even the vaccinated were vulnerable, causing some breakthrough cases. 

It soon became clear why delta wreaks so much havoc. People infected with delta make more of the virus and spread it for longer than people infected with other variants, researchers reported in Clinical Infectious Diseases in August. As a result, delta infections are more contagious. Consider two scenarios in a community where no one has immunity to the coronavirus: A person infected with an earlier version of the virus — the one first identified in Wuhan, China, that set off the pandemic — might spread it to two or three others. But a person infected with delta may transmit it to five or six people.

Delta owes its success to mutations in some of its proteins. Take, for instance, a mutation called R203M in the coronavirus’s nucleocapsid, or N protein, located inside the virus. This mutation may increase the amount of viral RNA that can be made or make it easier for the N protein to do its job, packing RNA into newly assembled viral particles, researchers reported in Science in November. 

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Mutations similar to delta’s have appeared here and there in other variants that proved themselves capable of spreading more easily or better evading the body’s immune defenses than the original virus. That includes alpha, first spotted in the United Kingdom; beta, first characterized in South Africa; and gamma, first noted in Brazil. The recently discovered omicron variant, first described in South Africa and Botswana, also shares some of the same mutations (SN: 12/1/21). 

Some of delta’s grab bag of mutations are identical to those found in other variants, while others change the same protein building block, or amino acid, in a different way or pop up in the same part of the virus. For instance, alpha and omicron also have the same mutation of the 203rd amino acid in the N protein, but it is a different amino acid change than seen in delta. And some mutations are entirely new to delta. 

Scientists don’t yet know the effect that all those changes have on delta’s ability to replicate or spread to others. What’s more, delta continues to evolve, picking up additional changes over time. But studies have zeroed in on the unique constellation of mutations decorating the virus’ spike protein. It’s the knobby protein studding each coronavirus that helps the virus latch onto and invade human cells. What looks like an individual knob is in fact composed of three identical pieces that fit together, each carrying the same set of mutations. 

Some of delta’s spike protein mutations may help the virus more easily break into cells, where it turns cell machinery into virus-making factories. Two of those, dubbed T478K and L452R, are advantageously located on the receptor-binding domain. This is the part of the spike protein that attaches to ACE2, a protein on the surface of host cells.

Other mutations show up in a region of the spike protein called the N-terminal domain, which is a known target of the immune system’s neutralizing antibodies. These mutations may help the virus evade those antibodies, which can stop the virus from infecting cells.

And yet two other mutations, P681R and D614G, may help prep newly made viruses to go out and conquer. Those mutations are nestled near the dividing line for two parts of the spike protein, S1 and S2. Those parts need to be split apart to allow the coronavirus to engage in the gymnastics needed to help it fuse with the membrane of its prospective human host cell.

Human cells actually aid in this process: Inside infected cells a human protein called furin nicks the spike protein between the S1 and S2 segments, opening the receptor-binding domain so it can better grab ACE2. The P681R and D614G mutations may make the spike protein easier for furin to cut. Once snipped, newly-made viruses are primed to infect other cells.

Taken together, these mutations help delta break into cells more quickly and perform several tasks better than other variants do. As a result, in 2021, delta was able to become the dominant variant in the world. 

Here’s how specific delta spike protein mutations may aid in a cell take-over:

illustration of D614G, L452R, and T478K mutations on the spike protein's receptor binding domain as it latches onto the ACE2 protein on the surface of a human cell
illustration of a TMPRSS2 protein cutting part of the spike protein so that the coronavirus can infiltrate the cell's membrane, add it's RNA, and create new virusesillustration of furin protein cutting the spike protein, which contains mutations P681R and D614G, of newly made viruses

Delta may be snippier than other variants. 

Mutations D614G and P681R may increase the number of spike proteins cut by furin on each newly made virus, better prepping the viruses to enter other cells.

D614G makes it easier for furin to make its snips. This preliminary cut happens in a different location than the TMPRSS2 cut. The mutation may also increase the number of spike proteins on each copy of the virus.  

Like D614G, P681R may also boost the number of spike proteins cut by the human cell protein furin, priming the newly made viruses to infect new cells. 

illustration showing antibodies attacking the spike protein on virus particles and blocking them from entering cells