Although the SARS-CoV-2 virus has been circulating for more than 2 years, it continues to disrupt global supply chains, overwhelm hospitals, and impact the daily lives of individuals around the world. Despite the advent of safe and effective vaccines that protect against COVID-19 infection, the SARS-CoV-2 virus appears steadfast in its refusal to exit our lives for good. As surges of the disease — particularly those caused by the SARS-CoV-2 Omicron variant — have begun to dwindle, there is increasing hope that this virus will soon transition to an endemic disease that we can officially put behind us. But that may be the wrong way of thinking about it.

We spoke with Erica Johnson, MD, about endemicity, what it means in the context of COVID-19 infection, and whether the transition of COVID-19 from pandemic to endemic is more of a philosophical quagmire rather than a scientific one. Dr Johnson is an assistant professor of medicine at Johns Hopkins University and the Chair of the American Board of Internal Medicine’s Infectious Disease Board.

There are many circulating opinions in the scientific community as to what exactly endemicity means. Some say endemicity constitutes a disease with stability, constancy, and predictability; some define it as a disease that concentrates in a specific geography; and others say that the predictability of a disease is not a prerequisite for endemicity. How do you define endemicity in regard to COVID-19?


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Dr Johnson: I think endemicity just refers to the virus and the causes of disease always being present in specific regions. In the case of COVID-19, it will continue to circulate in most of the regions in the world, based on what we know so far. I think rates may rise at predictable intervals, or at certain times of the year, and then revert back to baseline levels at other times. But I don’t think the definition of endemic precludes that many, or essentially all, regions of the world are going to continue to be impacted by this, just like we see with influenza, for example.

Although you caution against predicting a timeline for when COVID-19 will become endemic, would you provide your best guess as to where we are on the path to endemicity in the COVID-19 pandemic: somewhere in the beginning, the middle, is it just on the horizon, and why?

Dr Johnson: We seem to be approaching the shift with COVID-19. I think it’s convenient to use the term endemic to describe where we are, but I think what is really happening is that societies are just learning to live with the virus. Both because of the availability of effective vaccines and better therapeutic options, and other public health tools to mitigate the impact. But also, because we’re going through this sociocultural shift right now. I think there’s that increased willingness to adapt how we use all of these tools, based on changes in the current situation with respect to COVID-19 transmission and I think that’s really what’s going on right now.

Would you say another way to describe endemicity is the amount suffering that a disease causes that people are willing to live? Perhaps this is more of a philosophical question.

Dr Johnson: I think it’s sort of a philosophical change. As a society, I think we get to a level of acceptance about what risks we can and cannot tolerate, because of the impact that that has on other aspects of how we conduct our lives. I don’t think that there’s a hard line in terms of when that happens. I think it’s a bit more fluid. I think the concept [of endemicity] and when it happens is very different from thinking about this from a biological standpoint. Biologically, I think it’s hard to say [when endemicity has occurred] until after it’s happened, and then, we’re looking back. I think, socially, we are clearly in a changing phase of the environment of the virus, right now, that changes because of the psychological impact [the SARS-CoV-2 virus] has had on all of us, to live under these circumstances for so long, and the increased appetite for wanting to routinize some of these public health measures in a way that allows us to just feel like we’re able to get back to life as normal, whatever that is.

Considering that the SARS-CoV-2 virus has notoriously been difficult to predict as it’s come in multiple waves and plateaus, as well as the difficulty in forecasting the emergence of new variants, why are you confident that there is a path to endemicity?

Dr Johnson: I think because, in a lot of ways, I feel like we’re already on that path.

Meaning the way that we’re thinking about the virus, and the way that we’re thinking about all the things that we have to do to adapt our life to the virus, have been changing, or are changing. We have a lot more tools to address the virus. Even as new variants emerge, I think that a lot of people are just socially ready to make that shift.

Seasonal influenza, which you mentioned earlier, is largely considered an endemic disease, yet it has some caveats. It appears to be predictable and reliable, but not necessarily stable, and it appears to be too global rather than restricted to a geographical location. In a single year, there may be 10,000 deaths attributed to the flu in the United States, but in other years, that number may reach 60,000.1 Do you believe this boom-and-bust cycle of seasonal influenza is the proper benchmark for what to expect in the endemic phase of COVID-19?

Dr Johnson: I think we have to expect fluctuations like that. By that, I mean, I think there are many other factors that impact rates of influenza [observed in each] season, whether that’s the dominant circulating strain, or how well the influenza vaccine matches [the dominant] strain in a particular year, or places that have mandatory influenza vaccination policies in place. Even [factors] like the acceptance of the need to stay home when you’re feeling sick. All of these different public health measures come into play [and] impact what we see in any given influenza season. Our experience with COVID-19 has already been pretty similar. There are many factors that impact why disease surges in some communities and then quiets down weeks later, only to rise again in a few months. I think we need to be prepared for something like this [to occur]. Although, of course, it’s hard to know exactly. But I think we all have a role to play. It’s ultimately up to us to ensure vaccination rates are [increased] globally. It is ultimately up to use to adopt appropriate control measures quickly when community transmission rates start to rise again, [and] to mitigate the impact of a sudden surge of cases within a community.

Diseases such as malaria, HIV, tuberculosis, and herpes simplex virus (HSV-1) often carry pandemic-caliber mortality rates and are typically concentrated in less wealthy parts of the world, yet all are considered endemic. Malaria, by itself, sickens upwards of 200 million people per year, and brings death to approximately 400,000, most of whom are children younger than 5 years.2 In consideration of these figures, and that it’s mostly only Western countries that have had plentiful access to COVID-19 vaccines and treatments, should people be excited about the prospect of COVID-19’s transition to endemicity in a global context?

Dr Johnson: You’re correct. These are serious endemic infections that carry very high mortality rates or are associated with very high degrees of morbidity. I agree that [to be] excited about the shift from thinking about SARS-CoV-2 as a pandemic virus to an endemic one is not quite right. Because the virus still carries the potential to cause severe disease, long-haul COVID, and death in some people, all of which are serious outcomes. I think people are responding to the notion that we’re starting to move from a sociocultural perspective to thinking about SARS-CoV-2 and COVID-19 as a normal part of everyday life [and] to make the measures that we use to control it much more routine. I think that gives people hope that communities can both return to normal activities and protect themselves from surges of COVID-19, as long as they’re willing to have reasonable public health measures in place to mitigate the impact of COVID-19 when community transmission rates inevitably [increase].

COVID-19 vaccines for children younger than 5 years may soon be authorized by the US Food and Drug Administration (FDA). Although many parents seem hesitant about the prospect of vaccinating their young children, and only 22% of children aged between 5 and 11 have received the vaccine3, what effect will vaccination rates among young children have on COVID’s transition to endemicity?

Dr Johnson: I think for many parents, part of adopting a mindset that SARS-CoV-2 and COVID-19 are a normal part of everyday life, for now, and then feeling more confident about the return to normal activities, is knowing that their children are as protected as they can be from COVID-19 infection. Increasing vaccination rates in young children and ultimately extending that to children under the age of 5, when we’re able to, is an important step towards this [transition]. Increasing vaccination [rates] in children [is] important because it raises the level of immunity to COVID-19 in a community. [Increased vaccine uptake] may guard against surges and transmission, or at least the surges and [cases of] severe disease that require hospitalization. I think all of this is necessary to move to this endemic phase, whatever that is.

You have stated that you’re not confident that a fourth COVID-19 booster will make a difference on this path to endemicity. Why?

Dr Johnson: It’s not clear whether an additional booster is needed beyond the current recommendation for a complete primary series and a booster for most adults. I think the data show that the protection against SARS-CoV-2 does wane over time, but the [risk for] hospitalization due to severe COVID-19 infection, or death from COVID-19, does remain very high with vaccination. The waning immunity is the reason for the recommendation of the booster, and that improves efficacy in the short term. I think we’ll have to wait a bit longer to see if a decline in efficacy for those who are up-to-date on vaccination, which means a complete primary series and a booster, starts to happen as well. I think we can take the evidence from this recent Omicron surge, where we saw that a primary series with a booster was clearly helpful in [decreasing the risk for] death and severe infection requiring hospitalization. I think we’ll just have to wait a little longer to find out.

If COVID-19  were to transition to be more like seasonal influenza, would you expect the COVID-19 vaccines to be modified each year, similar to the way in which influenza vaccines are modified each year to target whichever strain of influenza virus is the most prevalent in the environment?

Dr Johnson: I think that that could happen if the reason for the pattern of increased transmission is because we are seeing different circulating [SARS-CoV-2] variants. It’s possible that this pattern of recurrent transmission would because we see the Delta [variant] again, after there’s waning immunity to Delta, or we see the Omicron [variant] again, because there’s waning immunity to the Omicron [variant]. I think we just don’t know. I would guess that because the rates of vaccinations globally are still not in the ideal place, [and] that other variants of interest — other variants of concern I should say — are probably in our future, we’ll just have to wait and see if any of them are more transmissible than what we’ve seen with the Delta [variant], and certainly, what we experienced with the Omicron [variant].

References

1. Centers for Disease Control and Prevention. Past seasons estimated influenza disease burden. Published 2019. https://www.cdc.gov/flu/about/burden/past-seasons.html

2. World Health Organization. Malaria. https://www.who.int/health-topics/malaria#tab=tab_1. Accessed February 24, 2022.

3. Hause AM, Baggs J, Marquez P, et al. COVID-19 vaccine safety in children aged 5–11 years — United States, November 3–December 19, 2021. Morb Mortal Wkly Rep. 2021;70(5152);1755–1760 doi:10.15585/mmwr.mm705152a1