COVID-19: What Do We Know About the Delta Variant (and Others)?
Like all living organisms, the SARS-CoV-2 virus evolves. During each infection, billions of new viral particles are produced. Some of these new viruses carry mutations.
Samuel Alizon, French National Research Institute for Sustainable Development (IRD) and Mircea T. Sofonea, University of Montpellier
This evolutionary process and the emergence of these variants have been studied in detail. We now know that in most cases, these SARS-CoV-2 variants are either not transmitted to new hosts or are “neutral,” meaning that the infections they cause are similar to those caused by non-variant (also known as “wild-type” or “historical”) viruses.
But sometimes some of these variants spread and begin to outcompete existing viruses. The most recent examples are known as the alpha, beta, gamma, and now delta variants. They first emerged in the United Kingdom, South Africa, Brazil, and India, respectively. Why? What do we know about their characteristics? What do we know about their ability to evade vaccination?
What is a variant?
The variants that have been making headlines for several months differ clinically and/or epidemiologically from the majority of SARS-CoV-2 coronavirus variants. Specifically, a variant is distinguished by at least one of the following four characteristics:
- Its transmissibility, in other words, its ability to infect more hosts;
- Its virulence, which is reflected in the severity of the symptoms experienced by infected individuals;
- Its waning immunity, which means that people who are already immune are less well protected (with, in the case of SARS-CoV-2, vaccine-induced immunity currently providing stronger protection than natural immunity);
- Its resistance to treatment.
In the case of COVID-19, this last point is not currently a major concern, as few treatments are available. Furthermore, these treatments are intended for the severe stages of the infection, during which transmission is limited.
The first variant was identified as early as spring 2020
The very first example of a SARS-CoV-2 variant—even though it is rarely described as such—emerged as early as the spring of 2020. Viruses carrying the D614G point mutation, affecting the gene that produces the spike (S) protein (which serves as the virus’s “key” to entering the cells it infects), emerged and spread. The underlying process was difficult to demonstrate, as the mutated form (carrying the D614G mutation) has a lower affinity for the ACE2 receptor than the wild-type form (in other words, it binds to it less easily), but this mutated form appears to degrade more slowly, which ultimately increases viral infectivity.
What is notable is that this “substitution” mutation—the replacement of one amino acid (the “building blocks” of proteins) in the S protein with another—occurred independently in several lineages. This is a classic example of parallel evolution. The SARS-CoV-2 coronavirus originated in bats. Its transition to a new host is significant because, from the virus’s perspective, it requires adaptation to different cellular environments.
The phenomenon of natural selection comes into play here: research conducted in the early20th century revealed that the further a population is from its evolutionary optimum, the higher the selection gradient, and thus the more likely it is that mutations conferring strong adaptation will be observed. Conversely, the closer the population is to an evolutionary optimum, the rarer these high-impact mutations are. In other words, observing significant parallel evolution at the start of the epidemic, when the coronavirus was found in a new host species, is not all that surprising.
Three variants of concern and six variants of interest
Beyond this initial example, it was primarily in late 2020 that three variants of concern were detected, now known as alpha (identified in the United Kingdom), beta (in South Africa), and gamma (in Brazil). All have been linked to major waves of the pandemic. The surprise was that these viruses carried more mutations in their genomes than average.
In France, estimates suggest that the Alpha variant is about 40% more contagious than the strains that were circulating previously. British data covering tens of thousands of patients also indicate that this variant is 50% more virulent.
As for the gamma variant and, to an even greater extent, the beta variant, immunological data suggest that they are less susceptible to immunity induced by natural infection, which would explain their rise in France in April 2021.
In addition to these three variants of concern, there are at least six variants of interest identified by the World Health Organization (WHO). They are being monitored because their genomes contain mutations found in certain variants of concern and because they have been linked to outbreaks of rapid spread.
Assessing the risk posed by variants is no easy task
It is extremely difficult to assess the danger posed by a variant based solely on its genome sequence. For example, Alpha variants carrying an additional mutation (E484K) initially raised some concern. In particular, mutagenesis studies showed that mutations at position 484 (as well as at other positions in the spike protein) likely allowed the virusto evade the immune response. However, it was subsequently observed that this mutation is not as problematic as when it is present in other genetic backgrounds (for example, in the beta and gamma variants).
This phenomenon, well known to geneticists, is called epistasis: even if two mutations, A and B, are beneficial to the virus when they occur in isolation, the presence of both in a genome can prove to be harmful. More generally, the expression of a gene can be strongly modulated by the expression of other genes; in such cases, knowing that a point mutation exists is insufficient to deduce its biological effect.
The Delta variant provided a second example illustrating the difficulty of predicting the epidemiological consequences of mutations.
The case of the Delta variant
This variant was first detected in India, where other closely related viral lineages were being monitored because they carried a mutation at position E484.
While, as with other variants, it is difficult to trace the exact origin of the Delta variant, it is suspected that its emergence may have been facilitated by the gathering of millions of people at a religious festival. It is important to remember that the more infections there are, the greater the number of variants produced, and the higher the likelihood that a variant will spread throughout the population.
Although data from India is limited, the United Kingdom’s extremely detailed and transparent epidemiological monitoring—particularly its reports on variants—allows us to learn more about the characteristics of the Delta variant.
It is now virtually established that this variant is more transmissible. Indeed, within households where people have been infected with the Delta variant, a higher proportion of household members are found to be infected. Furthermore, preliminary data from Scotland (from the same reports) suggest that infections with the Delta variant could lead to more hospitalizations. Finally, the question of immune escape remains open.
As for vaccine-induced immunity, no impact on hospitalizations has been observed so far (protection remains around 95%), and the effect is limited when it comes to reinfection (a 10% reduction in protection with two doses compared to infection with the Alpha variant). Natural immunity, meanwhile, is becoming increasingly difficult to quantify as vaccination coverage increases.
In summary, the Delta variant appears to be more contagious than other known variants, but its ability to evade immunity seems to be lower than that of the Beta and Gamma variants. This case illustrates the major role of epistasis and the limitations of tracking mutations individually.
The Delta variant in France: difficult to detect
In France, accurately identifying the Delta variant has been difficult, just as it was with the Alpha variant, because only a small number of samples that test positive for COVID-19 are sequenced. However, screening for specific mutations in nearly all positive tests has made up for this lack of precision and allowed results to be obtained quickly.
Analysis of screening test results through June 8 indicated that this variant already accounted for nearly 10% of cases in the Île-de-France region by mid-June, and that it appeared to have a significant transmission advantage over other circulating viruses.
More detailed analyses based on data through June 21 showed that, in France, the Delta variant had a transmission advantage of about 70% over the Alpha variant in several regions.
The good news is that vaccination provides strong protection against infection with the Alpha variant (according to UK data, a 30% reduction in risk with one dose and an 80% reduction with two doses) and offers extremely strong protection against severe disease (an 80% reduction in risk with one dose and a 95% reduction with two doses). This explains why the spread of this variant is observed primarily among younger, less vaccinated populations.
What steps should be taken?
Today, we have everything we need to prevent hospital systems from becoming overwhelmed again in the near future. Vaccination is crucial, as it provides extremely effective protection against severe cases. But it is not enough, for several reasons.
On the one hand, because in order to fully lift protective measures and return to pre-2020 health protocols in urban centers, more than 80% of the French population will need to be vaccinated (it should be noted that while 95% of adults in France are vaccinated, this corresponds to 75% of the total population). On the other hand, even if the most vulnerable will likely be protected by fall, allowing this virus to circulate widely among younger people could have a health impact that is difficult to estimate, given the high virulence of the Alpha variant and the unknowns associated with long COVID.
Furthermore, although this virus rarely causes death among younger people, current figures indicate, depending on the source, 1 to 6 deaths per 100,000 infections among 15- to 19-year-olds. Finally, as long as SARS-CoV-2 continues to spread widely, new variants will continue to emerge, and—as evolutionary biologists would expect—this virus has not become benign. On the contrary, the most contagious variants also appear to be the most virulent.
We must therefore avoid repeating the mistakes of summer 2020 and take advantage of the low incidence rate (fewer than 3,000 new cases per day as of July 1, according to our estimates) to finally allocate the resources needed to effectively implement a policy of testing, contact tracing (or retroactive tracing), and isolation on the ground. We must also rely on the scientific evidence supporting the decisive role of aerosol transmission to equip enclosed spaces (particularly schools) by the start of the school year with measures to reduce the risk of spread (air circulation, ventilation, reduced capacity).
Compared to last year, we now know much more about how SARS-CoV-2 spreads, and we now have a range of safe and effective vaccines. This knowledge and these tools should enable us to avoid a repeat of the dire situation we experienced last fall and winter.
Samuel Alizon, Director of Research CNRS, French National Research Institute for Sustainable Development (IRD) and Mircea T. Sofonea, Associate Professor of Epidemiology and the Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.