The Delta variant is serious. Here’s why it’s on the rise. The virus variant that caused infections to spike in the U.K. is now spreading in the U.S., and experts are very worried.
With vaccination rates slowing in the United States, and other countries struggling to secure vaccines, public health experts have growing concerns that the so-called Delta coronavirus variant, first identified in India in March, could trigger dramatic rises in cases and deaths in the U.S. and the world. The Delta variant already accounts for 18 percent of cases in Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming, and about six percent of cases nationwide. It has already spread to more than 70 countries and is now the most dominant variant in India, the United Kingdom, and Singapore. Last week, Delta caused more than 90 percent of the new COVID-19 cases in the U.K., leading to a 65 percent bump in new infections since May 1. On Monday, to curb Delta’s spread, the U.K. government decided to postpone “freedom day,” which would mark the end of public health restrictions.The Delta variant is 60 percent more transmissible than the Alpha variant—first identified in the U.K.—which in turn was about 50 percent more transmissible than the ancestral Wuhan strain. “It’s a super spreader variant, that is worrisome,” says Eric Topol, founder and director of the Scripps Research Translational Institute. It has features that enable escape from the immune system and is perhaps more evasive than the Beta variant (B.1.351) first identified in South Africa, which was the worst until now, says Topol. “Plus, it has the highest transmissibility of anything we’ve seen so far. It’s a very bad combination.”
Dismayed by the trajectory of Delta in the U.K., Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, warned President Joe Biden last week, “we cannot let that happen in the United States.”
The President echoed those sentiments, tweeting “Folks, the Delta variant—a highly infectious COVID-19 strain—is spreading rapidly among young people between 12 and 20 years old in the U.K. If you’re young and haven’t gotten your shot yet, it really is time.” A complete dose of a COVID-19 vaccine is still effective at preventing serious COVID-19 stemming from Delta infection.
Why is the Delta variant so scary? Freely circulating viruses, especially coronaviruses and influenza viruses, which encode their genetic instructions using the molecule RNA, mutate frequently and randomly due to copying errors introduced as they replicate in their human host cells. Some mutations enable the virus to evade antibodies; some enhance its ability to infect a cell; others go unnoticed since they yield no benefits or can even weaken it.
The key to Delta’s success is the collection of mutations the variant has accumulated in the spike protein, which covers SARS-CoV-2 and gives the virus its signature crown-like appearance. These mutations have changed the spike, and, as a result, some of the existing antibodies may not bind as tightly or as often, explains Markus Hoffmann, an infectious disease biologist at the Leibniz Institute for Primate Research in Germany. Hoffman and others have shown that Delta and its closely related Kappa variant evade antibodies that were generated through previous infection and vaccination. Some synthetically produced antibody therapies, like Bamlanivimab, were unable to neutralize the Delta variant; but others such as Etesivimab, Casirivimab, and Imdevimab were still effective.
The Delta variant has mutations on the spike protein that alter how it interacts with the ACE2 receptor protein, which is found on the surface of lung and other human cells and is the portal to invade the cell. The mutation at location 452 of the spike protein, which is also present in some of the California variants, appears to make the virus more transmissible and helps it spread through the population, explains Mehul Suthar, an immunologist at the Emory Vaccine Center.
If a mutation gives a virus a fitness or reproductive advantage, that mutation tends to evolve independently around the world. Delta, its closely related variants, and the highly contagious Alpha variant all carry a mutation at position 681 of the spike protein, which is thought to be an evolutionary game changer that also makes it easier for SARS-CoV-2 to invade the host cell and spread. This mutation is fast becoming common in COVID-19 viruses around the globe.
In addition to these mutations a recent study, not peer reviewed, shows a variation at position 478 on Delta’s spike that enables the virus to escape from weak neutralizing antibodies. This mutation has also become increasingly common in SARS-CoV-2 variants in the U.S., Mexico, and Europe since early 2021.
“When you have all of these mutations, then you start seeing a difference in infectivity (of the virus),” says Ravindra Gupta, a professor of clinical microbiology at the University of Cambridge, who has shown in an unpublished study how these variants can have a greater potential to cause disease.
Vaccines less effective against this super spreader. The data from India and the U.K. show that Delta has emerged as the dominant variant in those countries within four to six weeks. That indicates Delta is more transmissible and infectious than the previous variants. There is emerging evidence that it can also cause more severe disease. For example, in Scotland it caused about twice as many hospitalizations than the Alpha variant, which already caused more severe illness than the original SARS-CoV-2.
“This combination of high transmissibility, high severity, and escape from vaccines makes Delta a very, very dangerous variant,” says Deepti Gurdasani, a clinical epidemiologist at Queen Mary University of London. Once Delta enters a country, it is going to spread rapidly. “It’s going to be quite hard to contain, and very likely will become the dominant variant in a matter of weeks. It could change the trajectory of the global pandemic.”
While vaccines are still effective against severe disease and hospitalization caused by the Alpha and Beta variants, they offer less protection against Delta. People who were vaccinated with one or two doses of the Pfizer vaccine produced lower levels of antibodies capable of neutralizing the Delta variant compared with the levels generated against Alpha and Beta. In the U.K., 31 percent of all confirmed Delta variant patients who needed emergency care had received at least one vaccine dose.
Similarly, a study under review revealed that after both doses, the Pfizer vaccine showed 88 percent effectiveness against symptomatic disease caused by the Delta variant compared to 93 percent against the Alpha variant. Two doses of AstraZeneca vaccine were 66 percent effective against Alpha but only 60 percent against Delta. But with just single dose of either of the two vaccines, the vaccine effectiveness was only 51 percent against the Alpha variant compared to 33 percent against Delta. This effectiveness falls below the 50 percent efficacy threshold the FDA had set for designing safe COVID-19 vaccines; in which a vaccine should prevent at least half of the vaccinated people from getting COVID-19 symptoms.
In other studies still awaiting peer review, researchers report that Delta was responsible for most breakthrough infections—which occur after full vaccination—in India leading to a cluster of such cases among fully vaccinated healthcare workers.
There are many vaccine candidates being rolled out around the world and since there are no agreed international efficacy standards, each vaccine might offer a varying degree of protection against new variants. “We need more information about the performance of some of the more widely available vaccines in other parts of the world,” says physician and virologist Benjamin Pinsky of Stanford University School of Medicine. “I think folks need to make sure they get vaccinated. And until they are fully vaccinated, continuing with public health intervention is very important,” he says.
A vaccine alone only slows down the progression of a contagious disease by increasing the herd immunity. Until that point, preventive measures such as social distancing and masking are proven strategies for curbing the spread of the virus.
With just 44 percent of the U.S. population fully vaccinated, the majority of people are still vulnerable. Relaxing public health restrictions and declaring victory prematurely could provide an opportunity for the Delta variant to surge–particularly in the fall.
A study, not yet published, suggests the possibility of seasonal variations in COVID-19 incidence based on analyses from a full year of the pandemic in Europe and Israel. While the virus’s seasonal trends may not be clear yet, says Topol, we do know that when people spend more time indoors with poor ventilation and low humidity the virus spreads more rapidly.
What is happening in the U.K. could occur in many places worldwide. “We should keep social distancing after vaccination, because there will always be possibilities of breakthrough infection because vaccines can still be imperfect against emerging variants,” says Kei Sato, a virologist at the University of Tokyo, Japan, who has been studying the effect of mutations on the transmission of Delta and other emerging variants.
“The more variants like this spread, especially in unvaccinated individuals, the more these viruses mutate and eventually pick up mutations that allow for more efficient antibody escape. This could, in theory, make the current vaccines even less effective against these variants.” Suthar cautions.
If we don’t take Delta seriously, “there will be a further wave in the U.S. We can already see the fall in cases has plateaued,” cautions Gupta. Topol agrees that if we ignore this variant “we’ll have a significant rise in cases in vulnerable areas, more hospitalization, and the pandemic here will last longer.”
Why do new SARS-CoV-2 variants spread more easily?
Random mutations allow new forms of the virus to better bind to human cells
VIRUSES, LIKE all organisms, have life-cycles. Theirs are parasitic, beginning when a parent virus infects another creature and hijacks its cells to make copies of itself. In the case of SARS-CoV-2, the virus that is causing the pandemic, this happens when it latches onto an enzyme called ACE2 on the membrane of some human cells and slips its genome through into the cell. This cellular invasion is helped by a protein that studs the surface of the virus, known as the spike. Changes to the spike, driven by genetic changes from mutation, alter the virus’ overall properties, particularly its capacity to spread through populations.
The mutable nature of viruses is rooted in the randomness inherent within the process of producing copies of any object, making errors unavoidable. As host cells churn out copies of SARS-CoV-2, errors occur, called mutations. The vast majority of viruses do not survive errors in replication. But some do, and may even thrive as a result of the changes, outcompeting ancestral viruses and spreading more efficiently through their host population. There are some parts of the structure of the virus that are better able to withstand mutations: the spike protein is the most tolerant to changes. Mutated viruses which survive and thrive are called variants. These started emerging in earnest from SARS-CoV-2 in November 2020, with the emergence of the Alpha variant and its subsequent detection in Kent, in the south-east of England. New variants must hold some advantage over old ones if they are to become the dominant form of the virus. That advantage could be won in many different ways, but for a respiratory disease like covid-19, one of the most important factors is transmissibility, how easily the virus passes from one person to another.
One of the first mutations to increase transmissibility was referred to as N501Y, sometimes known as “Nelly”, one of eight mutations that characterised the spike protein of the Alpha variant. The mutation’s technical name is relatively straightforward once you understand that it is referring to changes in the virus’ genome, and this to the amino acid structure for which it encodes. The “501” means that the change is happening to the 501st amino acid in a chain of 1,273 that comprise the spike. The order and composition of these amino acids is dictated by a matching genome sequence, so that “501” refers to both the position on the genome and the position on the amino acid chain. “N” is short for asparagine, which in N501Y is swapped out for “Y”, which is tyrosine. Since different amino acids have slightly different chemical properties, this swap has an impact on the structure of the spike protein. As a result, the way electrical charge is distributed across it changes. This alters the shape of the protein slightly as areas of positive electrical charge attract areas of negative charge. Thanks to these dynamics, N501Y allows a crucial part of the spike to twist around by about 20 degrees, letting it find a more snug fit with the ACE2 receptor. Better binding occurs as a consequence, which means that any copy of the variant which enters the body is more likely to find its target and start replicating. This increases transmissibility. Other mutations perform a similar trick, freeing up different parts of the spike in different ways so that it may bind more effectively to ACE2.
Changes to the shape of spike are not the only way to increase transmissibility. Delta, the variant which was first detected in India and which is currently spreading around the world, appears to be even more transmissible than Alpha and the other variants. Quite why is not clear, as the detailed structural studies of Delta’s spike have not yet been completed. But Ravindra Gupta, a molecular virologist at Cambridge University, and his colleagues argue that Delta’s increased transmissibility is down, in part, to a mutation at site 681. This is the point on the spike where, after it has bound to ACE2, the protein is cleft in two. Dr Gupta says P681R, helped by two shape-modifying mutations elsewhere, makes it easier for the protein to be cut up and thus get into cells. Its presence also means that, once a cell starts producing particles, their spike proteins can get on to the cell’s surface pre-cut. That can lead to virus particles which are shorn of the parts which antibodies recognise and ready to fuse with any nearby cell. It can also encourage infected cells to clump together with others.
