Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine, is a physician-scientist who studies the interaction between human cells and deadly pathogens, including HIV-1, Ebola virus and SARS-CoV-2. His research into the significance of SARS-CoV-2 mutations received support early in the global pandemic from the Massachusetts Consortium on Pathogen Readiness, a collaborative effort that includes scientists and clinicians from Harvard; MIT; Boston University; Tufts University; University of Massachusetts; and local biomedical research institutes, biotech companies and academic medical centers.
Dr. Luban talked about what many scientists and public health experts describe as an endemic stage, the eventual equilibrium in which society learns to live with the SARS-CoV-2 virus. The interview has been edited for clarity.
What is meant by endemic in the context of a virus?
Jeremy Luban: The term endemic is being used to describe an eventual state in which we have reached a kind of détente with SARS-CoV-2. When this virus infected the first human beings in 2019 it was a brand-new infectious challenge that none of us had ever seen before. Whenever you introduce a new infectious agent into a population there is the potential for dramatic things to happen.
When Europeans first arrived in the Americas, for example, highly pathogenic viruses were brought with them that had never been seen by the population here in the Americas. As a result, millions of people lost their lives. Similarly, SARS-CoV-2 has killed millions of people because we had never been exposed to this pathogenic virus before.
Now that the SARS-CoV-2 pandemic has been raging for two-and-a-half years, most of us in Massachusetts have either been vaccinated against, and/or infected by this deadly virus. If we get to the point where the virus continues to spread and infect us, but it rarely causes severe disease because most of us have some immunity against it, we would say that SARS-CoV-2 has become endemic.
We have a model for what might happen with SARS-CoV-2, which is the model of the seasonal coronaviruses, which are virus cousins of SARS-CoV-2. We know about four of these viruses but there may be more out there. We’ve all grown up with the seasonal coronaviruses; certainly, by the time we’re teenagers we’ve all had them. We consider them common cold viruses.
It appears to be the case with these viruses, that if we’re young when we’re first infected, and we are not immunocompromised, we tend to have mild disease. There are exceptions and clearly SARS-CoV-2 has killed very young people, but the outcome tends to be milder disease if you are infected with these viruses as a child.
So, that could be where we’re headed with SARS-CoV-2. I think there are plenty of virology experts who are entertaining this as a possible end game. That is, once we’ve all seen it—either directly being infected by the virus and getting sick from it or getting vaccinated sufficiently—that we will get to this stage that the media has talked about a lot, this idea of herd immunity that keeps us from getting sick enough that we require hospitalization or that we die. Then the virus moves more into the background and is no longer the front-page story the way it’s been for the past two-and-a-half years.
How are we tracking the evolution of this virus?
JL: The technologies that we’re applying to track these viruses are relatively new. The kinds of sequencing tools that were applied here were arguably first applied to the Ebola virus disease outbreak in 2013 to 2016 in West Africa. So we’re learning a lot in real time about this specific virus, SARS-CoV-2, but also more generally about how people and infectious diseases interact with each other.
How can we tell if we’re approaching an endemic stage soon?
JL: We don’t know for sure, but it is interesting to compare our current situation with the fall of 2021. We were coming out of the wave of deadly infections with the delta variant and people had the sense that we were reaching an equilibrium with the virus, that things were finally going to quiet down. Then, on Thanksgiving we learned that the omicron variant was on its way and shortly thereafter came the explosion of COVID-19 cases with hospitals filling up and many people dying.
Now, as we approach the fall, we are in a different place. Many more people have developed a level of anti-SARS-CoV-2 immunity, from vaccination and/or infection. We’ve learned that boosters have an important role to play in terms of protecting against severe disease, though there are still big proportions of the population that haven’t been boosted.
But it’s possible that this coming fall is going to be the first relatively normal period for us since the beginning of the pandemic. It may be the beginning of the real endemic phase for us, where most people who get infection have a common cold. But we don’t know that with any certainty, and with SARS-CoV-2 we have to be prepared for the worst.
How might social behavior change when the virus is endemic? Will people go back to 2019?
JL: I think it’s likely that we will go back toward a situation like what we had pre-pandemic. Before SARS-CoV-2 there were other respiratory viruses that are plenty deadly. So, you know, most people don’t take influenza virus very seriously. But it is a serious killer in the United States. There are years when tens of thousands of people die from influenza infection. People who work in medical centers or are elderly are expected to get vaccinated every year. So, I think it’s likely we’re going to end up going toward something like the situation with influenza virus, where at least people at risk for severe disease are going to require annual vaccination.
What are considerations to keep in mind to prevent the pandemic from getting worse again?
JL: When we think about our response to the virus, we have to consider different perspectives. We have to think of the perspective of the individual person. We have to think also about our community, whether our actions will affect other people. And then we have to think at the global level, what are the consequences for our country and for the world?
If our hospitals are overrun with people being treated for SARS-CoV-2 and we don’t have the capacity to take care of those people, everyone suffers, whether they’re in need of medical care for SARS-CoV-2 or something else. If the burden of severe cases starts to rise it will be obvious that something needs to be done.
But we have tools for monitoring the virus that we did not have at the beginning of the outbreak, that we did not even have in place a year or so into the outbreak, that we can use to give us warning signs before we get to that point.
What is your outlook now on this evolutionary phase of the SARS-CoV-2 pandemic?
JL: I’m optimistic about the outbreak. Clearly the virus is capable of mutating and escaping our antibody responses, and we know it’s likely that kind of thing is going to continue. But underneath that, we can see that certain aspects of the immune response have been pretty solid; the ones that keep you from going to the hospital, the ones that keep you from requiring intubation and intensive care treatment, the ones that keep you from dying.
We can see now that, despite the fact that the numbers of people infected currently are high, we’re not seeing the same enormous numbers of people in the hospital that we saw in previous waves. I think that’s a reflection of the immunity that people have acquired with from vaccination, vaccine boosting and from prior infection.
How might the research agenda be affected by phasing into endemic stage? What would you want to be researched next?
JL: There are a couple of topics that are high priority. One area of investigation concerns the evolution of SARS-CoV-2. How great is the capacity of the virus to change and where might it go in the future? The virus has surprised us quite a bit over the course of the pandemic and we have to entertain the possibility that it will come up with new tricks and surprise us again.
We’ve been working on HIV-1 vaccines since the 1980s and we still don’t have one. With the success of the SARS-CoV-2 vaccines at preventing severe disease we dodged a bullet. But SARS-CoV-2 has shown itself to be capable of escaping from the immune responses that prevent transmission of the virus from person-to-person. So, an important research question going forward is whether we can develop vaccines that will prevent transmission, in addition to preventing severe disease.
Another question concerns the long-term effects of SARS-CoV-2 infection. There are many indications that SARS-CoV-2 can have long-term effects on people’s health, sometimes called long COVID. We know little about these long-term effects and this is a very important area of research.
Related UMass Chan news stories:
Mass Consortium on Pathogen Readiness awards COVID-19 research funding to three UMass Medical School projects
New research by Jeremy Luban examines cause of inflammation in HIV-1
Luban, Morrison elected fellows of the American Academy of Microbiology
