With just 48 percent of the U.S. population fully vaccinated, and other countries struggling to secure vaccines, public health experts are concerned that the Delta variant—the most dangerous and transmissible form of the coronavirus to date—will trigger dramatic surges in cases and deaths in the U.S. and around the world.
First identified in India in March, Delta is now the dominant variant in the U.S. and accounts for more than half of new infections, according to the latest data from the Centers for Disease Control and Prevention. It has spread to more than 90 countries and is also the most dominant variant in India, the United Kingdom, Russia, Israel, Singapore, and more than a dozen others.
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 in California.
Delta has features that allow it to evade some of the body’s immune system defenses, says Topol. “Plus, it has the highest transmissibility of anything we've seen so far. It's a very bad combination.”
In the U.S., Delta is responsible for more than 50 percent of new COVID-19 cases, up from 26 percent the week ending June 19. In parts of the Midwest and the Mountain States, where vaccination rates are lower, genetic analyses of virus samples suggest Delta could account for more than 80 percent of cases, said CDC director Rochelle Walensky during a press briefing on Thursday. She also presented data showing that less than 40 percent of residents were vaccinated in the roughly 170 U.S. counties with the highest case rates. Data from the past few months suggest that 99.5 percent of people who died from COVID-19 in the U.S. were unvaccinated. “So deaths were preventable with a simple, safe shot,” Walensky added.
Indeed, data show that a complete dose of a COVID-19 vaccine is still effective at preventing serious illness from Delta infection. A study published yesterday in the New England Journal of Medicine showed that both the Moderna and Pfizer-BioNTech mRNA vaccines will likely protect against Delta, though not as well as they did with previous variants.
A separate study estimated that two doses of the AstraZeneca or Pfizer vaccines will be be 60 and 88 percent effective, respectively, against symptomatic disease caused by Delta. And there is direct and indirect evidence that the single-shot vaccine from Johnson and Johnson is effective against the Delta variant, according to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
However, a single dose of either mRNA vaccine, or a previous natural infection, barely inhibited the Delta variant, write the authors of another study published yesterday in the journal Nature.
Alarmed by the reduced efficacy against Delta, Pfizer is planning to ask for FDA authorization for a booster dose of its vaccine within the next month. Pfizer and BioNTech also announced on Thursday that they had developed an updated version of their COVID-19 vaccine that would specifically target the Delta variant. The companies expect to begin clinical trials in August.
“The only conclusion one can reasonably come to … is please, get vaccinated. It will protect you against the surging of the Delta variant,” Fauci said at a press conference on Thursday.
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. Some synthetic 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 moretransmissible 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 studyhow 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 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 vaccinatedhealthcare 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.”
Editor's Note: This article first published on June 16, 2021. It has been updated to include new information about Delta and additional comments from experts.