When Does COVID Normalcy Begin?

Larry Corey, MD

When can we declare the SARS-CoV-2 pandemic over?

For some people, a battle is over when it is clearly won or lost. Our fight with COVID-19 doesn’t fit into such tidy categories.

The term endemic, at least in epidemiology, means chronic. It’s a constant presence, usually of an infectious organism, at some steady level. If a virus is endemic, that means it hasn’t been eradicated. There is no vanquished opponent and no real victor.

This is closer to what we’re seeing with SARS-CoV-2.

This virus will be with us for decades, if not forever.

A virus with staying power

Delta and Omicron show that this coronavirus has endurance. SARS-CoV-2 has demonstrated it has incredible talent and “natural” ability to antigenically change/mutate over time to enhance its transmissibility and ability to escape human immunity. One would expect, certainly we in the virology community all hoped, that SARS-CoV-2 would behave like other endemic human coronaviruses.

In other words, it would circulate, bother us every few years, but because of preexisting immunity, it wouldn’t pose a serious threat over the long run.

The non-SARS human coronaviruses are included within the common cold complex of infections rarely causing significant medical problems or mortality. We largely ignore them for this reason. SARS-CoV-2, including Omicron, is not in this category. SARS-CoV-2 will likely have claimed the lives of 1 million people in our country alone by June.

The least virulent variants, Omicron BA.1 and BA.2, still cause pneumonia and death—not as frequently as Delta, but a lot more than other human coronaviruses. It is still a COVID-19 virus. Clinically, Omicron is not a trivial disease in many people, even those previously vaccinated. Recently released data from California showed that among the COVID-related deaths between Dec 12 and Jan 25, 71% were in unvaccinated people, 24% in “fully vaccinated” and 5% among those boosted.

Again, this illustrates that all SARS-COV-2 strains are “variants of concern.”   

The other aspect of SARS-CoV-2 that ensures its extended presence on this planet is its ability to enter into the animal reservoir. Today, humans are clearly the predominant reservoir for the SARS-CoV-2 virus, but it is present in an ever-growing number of species including deer, mink, rodent, antelope, and the occasional cat or dog.

Living with COVID-19

When an infectious organism moves into an endemic phase, it means coming to terms about living with the virus in our midst. This is just not a biomedical definition. Biomedically, you could assign a quantitative measure—a milestone to be reached at which point we could breathe a collective sigh of relief. But what is that signpost? Is it 100,000 cases a day, 100,000 deaths per year? Or 10,000 cases a day? And 1000 deaths a year? Do we get different answers by race or political party? So, who decides? Does it matter what is decided?

During the COVID-19 pandemic, we have seen excess mortality, a term used to describe the number of deaths from all causes above and beyond what we might expect to see under otherwise “normal” conditions. Twenty to thirty percent of the deaths from COVID-19 are not written down as COVID-19–related but they occur at a much higher rate than the pattern seen for decades when COVID-19 was not around.

For the last year, this has been seen most prominently in the 30- to 50-year-old age group. How does this “excess death rate” happen? In many people, the SARS-CoV-2 virus travels beyond the nose and lungs and invades the heart, kidneys, and vascular beds of many organs. This tissue damage results in heart damage and blood clots that lead to organ damage. Those that suffer these problems often do not have COVID-19 directly attributed in their death certificate. But the death is still recorded and shows up in excess mortality data. As a physician, I would like to see this excess mortality metric seen during COVID-19 go back to normal (pre-COVID-19) as the medical definition of attaining endemicity. But in the end, I don’t think this issue of defining when COVID-19 is endemic is really that important except to the people who monitor this disease for medical and economic impact.

I don’t really think that “When does the pandemic end?” is the important question to ask, but rather when does normalcy return?

The meaningful metric of when does the pandemic end lies more in the sociological/behavioral arena than in case counts. Endemic really means that we as a society cope with the virus by using widely available countermeasures which will let us return to “normative” behavior.

Does that mean attending school without a mask? Or walking around indoors at the stadium without a mask? Or does that mean just feeling like, hey, I can go to a basketball game or a football game and if I do get COVID-19, it’s no big deal? It’s really knowing—on an individual and collective basis—that the effectiveness of available countermeasures no longer pales in comparison to the risk of infection and its consequences, and we can resume our lives.

Normalcy and assessing risk

We assess normalcy through individual risk assessments. It’s something we have done for all other respiratory illnesses. During influenza season, we get flu shots that are usually 50% to 60% effective. We all know we could get flu for a few days. But we also know the vaccine and oral antiviral treatments keep us out of the hospital. Our lives aren’t upended. We walk around, do our normal things each day, and don’t worry so much about flu.

We tolerate influenza A with a large number of cases and 30,000 deaths a year. When we get flu, we don’t strictly quarantine from everyone around us, worry about becoming hospitalized, or be told by society that we have to do X, Y, or Z, that will alter our lives.

Is that how we will eventually perceive SARS-CoV-2? It’s still too early to say. The problem is that COVID-19 is a considerably more complicated disease than seasonal influenza and the levels of excess mortality that we have seen from the SARS-CoV-2 virus exceeds that of seasonal flu, especially in the 30-to-55-year-old age group.

So endemicity, to me, is when we make widely available all the effective countermeasures we can, so we collectively feel that opening up our society fully is not only possible but a reachable goal.

How close are we?

Not a one-size-fits-all solution

Our vaccines, at the moment, don’t give us the level of confidence that we had a year ago, prior to the emergence of the variants. Many people are worried about getting infected.

But if we had oral antivirals widely available and implemented programs to properly administer these, or the more expensive monoclonal antibodies for older, higher-risk populations, and immune-suppressed individuals, I think we could get to behavioral endemicity.

The manufacturers are working quickly to increase available supplies. But even after supplies are made widely available, it will take work to implement and socialize—people need time to absorb the possibilities of what endemic means to them personally. Some people are more risk averse than others. But what will occur is that we’ll have more options and can make decisions based on a personal risk assessment.

Can I go to a movie theater and sit shoulder to shoulder with a stranger? Am I safe enough to eat indoors at my neighborhood family-style restaurant with 50 people eating, talking, and laughing? What about an indoor basketball game or a concert hall, even with its vast ceilings, and yet 2,000 people present?

These are the kinds of questions each of us will have to assess and answer in our own lives.

Reaching higher

A second strategy I think we must pursue is improving our vaccines so they prevent acquisition altogether. No breakthroughs, no sickness, no hospitalizations, no complications, no anything.

The monoclonal antibody work in COVID-19 treatment suggests that at really high antibody neutralization titers we appear to prevent people from acquiring the virus in the first place. We have some evidence that when the vaccine matched the ancestral strain, in the first couple of months, perhaps 40% of the time it prevented people from becoming infected altogether.

My own bias is that if we could make vaccines that achieve the same level of neutralization that we see in the monoclonals — currently 10 times higher — we might be able to prevent acquisition of the virus and truly reduce the widespread dissemination of disease.

The COVID-19 pandemic and its ubiquitous impact has startled—if not frightened—everyone. Every economy in the world has suffered, every community has been touched, every person in some behavioral way has altered their life. We all long for our own personal normal, which today seems just beyond reach because of the setbacks the variants have dealt us.

So, while our scientific triumphs against COVID-19 are incredibly impactful and praiseworthy, I’m raising the bar to say we need to improve them and make them better. Importantly, I’m confident we can do better. Science can—and should—up its game to match its cunning opponent. Pursuing better with our best gives us a fighting chance to emerge victorious with a new normal that feels possible for us all.

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

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