What makes Covid-19 delta variant such a threat? Ten questions answered

The delta variant has some characteristics that give it a better chance of causing an infection, which means it escapes initial shield provided by antibodies, but vaccinated people are at a lower risk

A surge in Covid-19 cases following the emergence of the highly transmissible delta variant has sparked fresh health concerns and raised questions about the safety and pace of reopening, even in places where vaccination rates are high such as the U.K. Sam Fazeli, a Bloomberg Opinion contributor who covers the pharmaceutical industry for Bloomberg Intelligence, answers questions about the variant and its potential threat. The conversation has been edited and condensed.

The delta variant has caused an uptick in Covid cases, especially among the unvaccinated but also among those who have received their shots. Isn’t it true, though, that vaccines offer good protection, even against this variant?

Well, it’s complicated by definitions. We know that vaccines were never 100% effective against an infection even before delta arrived. In the trials of Pfizer Inc.-BioNTech SE and Moderna Inc. vaccines, for example, we saw efficacy over 90%, meaning very few people tested positive for the virus. What was critical, though, was that vaccinated people in these trials were 100% protected against severe disease or hospitalization. The delta variant, as we will discuss below, has some characteristics that give it a better chance of causing an infection, which means it escapes the initial shield provided by antibodies. But vaccinated people are still at a far lower risk of developing severe disease, or if they do, their symptoms resolve more quickly. However, let’s not be under any illusions — people will still die from Covid-19 even if they are vaccinated, but in far lower numbers than if they were not.
 

What makes delta such a threat? How does it work?

The delta variant has developed certain mutations that make it more pernicious than its relatives. It has become better at infecting cells, partly by virtue of being able to somewhat evade antibodies in either previously infected or vaccinated people. Once inside cells, it is better at replicating. Evidence for this is confirmed by much higher amount of virus (viral load) in the nasal swabs of people who are infected with delta compared with those seen in the first wave of the pandemic. That may come from a process called syncytium formation, in which infected cells fuse with normal neighbors. The process helps the virus hide from the immune system and replicate faster. The delta variant seems to make bigger clusters, which helps it create more potentially infectious copies. A higher viral load also means that an infected person may exhale more virus particles, giving it a better chance to find its next victim. All of this leads to a much higher “fitness.”

What are the risks of contracting a “breakthrough” infection?

Again, we need to be very careful here. Breakthrough infections are not at all surprising, given that we knew the vaccines were never 100% effective against an infection. And the variants are eroding their efficacy in this setting. The virus infects people through the lining of their respiratory tracts, otherwise known as the mucosal membranes. These areas may not have as many vaccine antibodies, which gives the virus a small foothold. But an infection alone may not be a reason for concern in vaccinated individuals. 

How severe are the breakthrough cases we’re seeing? How concerning is it that even populations with high vaccination rates, such as Israel and the U.K., are seeing more of these?

Fortunately, we are not seeing breakthrough disease, i.e., the vaccines’ effectiveness against severe disease and hospitalization is still very high regardless of the individual variant. And remember that if vaccinated people do get an infection, their immune system will respond and actually cause some of the symptoms that we are used to with other infections, such as headache, a stuffy nose, and muscle/joint ache. Obviously people are not the same — some will have a much stronger antibody response to a vaccine than others and their immune system response to an infection will also be different, meaning different cold/flu-like symptoms. And with time a decline in antibody levels in some people who started out with a weaker immune response could permit a mild infection.

Are even mild breakthrough cases a concern?

There are several issues here. One is that if you get a mild infection, then you can pass that along to someone who is not protected, though studies show this transmission is lowered in vaccinated people. You also have a risk of driving a new mutation in the virus, which ultimately makes it even better at infecting vaccinated people. This is less likely, though, given that viral replication and duration of infection is reduced such that it may not have enough time to evolve new mutations. One important question is whether vaccinated people with mild infections have the same risk of long Covid. That is the one risk that I see in a world that accepts mild Covid infections as normal.

Is a person’s risk of a breakthrough higher depending on which vaccine they received?

Much of the data we have on this front is from lab tests, which can only tell you so much. This data suggests that the mRNA vaccines are better than the so-called adenoviral vaccines such as AstraZeneca Plc’s and Johnson & Johnson’s. Real-world data, in which matched groups of vaccinated and unvaccinated people are compared, so far seems to suggest that the Pfizer-BioNTech vaccine has a higher effectiveness in preventing a mild infection by delta than the AstraZeneca vaccine, based on research published in the U.K. The effectiveness of the Pfizer-BioNTech vaccine appears lower in Israel, based on information from the Ministry of Health, but we need much more detail to be able to assess why there is a difference between the U.K. and Israel. I also think we will find that the J&J vaccine has a lower effectiveness against mild disease. But the same types of analyses suggest that they are similarly effective against severe disease and hospitalization.

What kind of precautions should a fully vaccinated person take, knowing the delta variant is a threat?

I will tell you what I do. I wear two masks when I go out into public areas like supermarkets and shopping malls where I don't know the vaccination status of people. If I am having friends around, I make sure I know who  is vaccinated and who is not, and decide on that basis whether we go indoors or outdoors. I still don't eat indoors in restaurants, and I avoid bars and pubs. I did take a plane the other day, and wore two masks and avoided crowded spaces as much as possible.

Many elderly people were the first to get vaccinated in the U.S. Should we be worried about the vaccine’s protection waning, and does the presence of the delta variant pose higher risks for that population?

We know that the mRNA vaccines were equally effective against the previous versions of the virus, regardless of age. They also prevented serious disease to the same extent. What we don't know is how delta behaves in older people and how their immunity evolves over time. So we should exercise caution while we figure this out.

Is it time to start rolling out boosters against delta?

I think we need to be prepared to do so, yes, especially if we continue to run our lives based on mild infection rates. We should prepare for both delta and beta, the variant first discovered in South Africa. But I am not sure the virus has finished with its evolution. Do we need boosters right now? I don't think so. But should we have vaccines on order just in case? Yes, I think we should.

What about children?

Children younger than 12 are a tough issue. The perception is that they don't get bad disease, which is true to some degree. But some are susceptible to truly bad cases. In some instances, a problem referred to as multi-system inflammatory syndrome (MIS-C) can develop. The problem is that much of the data in terms of risk to children is based on a time when we had lockdowns and many people were educating their kids from home. Also, we didn't have delta. So we are at risk of a significant rise in cases when children return to school, often without masks, in September. And then we have the added problem of a resurgence in cases of respiratory syncytial virus (RSV), which was heavily suppressed during the past 12 to 18 months, driven by masking and lockdowns. RSV is normally the leading cause of acute respiratory hospitalizations in infants and young children, as well as the elderly. Most infants are born with protective antibodies passed on to them by their mother, but this won’t be the case for recent newborns. So the risk is these children could catch both RSV and Covid-19 at the same time. We have no idea what this means in terms of health outcomes