We are experiencing a COVID-19 pandemic that has dramatically changed the way we work, play, and live. For that to change — when we can say that we have crossed the line from pandemic to endemic and live our lives as before — we need to understand what we can reasonably expect from the immunity induced by vaccination and natural infection.
Both will protect against serious illness, which causes people to be admitted to the hospital or intensive care unit. But neither, over time, will be highly effective at protecting against mild illness, which causes a few days of fever, cough, congestion, and fatigue.
Protection against severe and mild disease is mediated by two separate immunological processes.
Protection against serious illness is afforded by immune memory cells. The good news about memory cells is that they are typically long-lived. The bad news is that they take time to be activated to fight against infection — too much time to adequately protect against mild illness, which occurs more quickly after exposure to the virus. But plenty of time to protect against serious illness, which takes longer to develop.
Protection against mild illness, on the other hand, is mediated by high levels of virus-neutralizing antibodies in the bloodstream at the time of exposure. The good news about neutralizing antibodies is that they can be highly effective at protecting against even mild infection. The bad news is that they are short-lived, lasting only three to four months after the last dose of vaccine.
The goal of the COVID vaccine — as is true for all vaccines — is to prevent serious illness. For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone. Three doses are required to induce high levels of protection against serious illness for people older than 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required.
For protection to last longer than a few months, another booster dose would be required. This is not a reasonable public health strategy. We can’t give booster dose after booster dose, all in the name of preventing mild illness. To avoid this, we need to change our thinking about COVID. Up to this point, we have done everything possible to identify and isolate people who have asymptomatic infection or mild illness. A zero-tolerance strategy.
Imagine if we did this for other respiratory viruses, such as influenza. Two years before SARS-CoV-2 virus entered the United States, influenza virus caused 800,000 hospitalizations and 60,000 deaths. One year before the COVID-19 pandemic, influenza caused 500,000 hospitalizations and 34,000 deaths. If we had a zero-tolerance strategy for influenza, we would frequently test people to determine whether they were asymptomatically or mildly infected with the virus and isolate them. And we would give two doses of vaccine during the winter to keep the level of virus-neutralizing antibodies high.
This would lessen the risk of spread. But it’s impractical. That’s why we label influenza virus endemic; we have learned to live with the current impact of this infection.
Over the next few years, a variant strain of SARS-CoV-2 might arise that resists protection against serious disease afforded by the vaccine. At that point, we will need a variant-specific vaccine. But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before.
Paul A. Offit is the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, a professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and a member of the FDA Vaccine Advisory Committee.