‘Endemic’ covers a lot of biology, but we’re probably not there yet for COVID-19

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Right up front, I’m going to repeat myself by saying that I think COVID-19 will become a disease that has endemic as well as epidemic states at some point in the future. But it’s probably not there yet. And that has no bearing on disease severity.

Why not yet? Because we are still seeing rapid-fire epidemics of the disease each year at any given site you look at (except for China which is the last location to drop a “COVIDzero” policy.

The wisdom among a number of people is that we still need to see more time pass before we can say that COVID-19 has an endemic aspect.

There are also statements that SARS-CoV-2 (the virus) will “never be endemic. It is an epidemic disease”. Never? That would be pretty bad given there are so few efforts remaining to control transmission now. And would be very different from the other airborne spread viral diseases we currently live alongside.

I wanted to get into some weeds on the nature of endemic diseases (not endemic viruses).

Some definitions

In any useful discussion, all parties understand what each other means if they work from the same definitions. Without definitions – as social media so often demonstrates – humans tend to rapidly go off on tangents talking at cross-purposes and getting nowhere.

Yes, definitions are super-important, but if they don’t use enough words, they can still fail to get us all on the same page. Apart from confusion and misunderstanding among experts, this can hinder the general public from applying terms properly; especially those people who like to apply knowledge to new things for themselves.

There are a lot of epidemiology definitions that sit in the “please use more words” space. As you’ll see below, some just don’t capture the complexity of the biology to which they are applied. Sometimes this leaves us with extra bits of info being bolted on but perhaps without any sort of consensus.

Below are a few definitions related to the word “endemic”. None of these would be hurt by having more words and some real-world examples. There are probably lots of books out there that do this, but I haven’t read them all yet!

Endemic disease

The first two definitions of ‘endemic’ from A Dictionary of Epidemiology below vary a little by version but basically link the word to a disease that is constantly present at a site or within a population.

For the disease to remain it needs to keep appearing – new cases have to occur be it through:

  • Infection – the Reffective needs to be on average, 1 – it can go up or down, but on average another person needs to be infected, or else the disease will eventually go away through recovery or treatment or death
  • Predisposition – new births of those with a genetic risk factor that means they are at higher risk of disease
  • Environment/lifestyle/income – those who will eventually acquire disease because their risks are higher

The constant presence of a disease or infectious agent within a given geographic area or population group; may also refer to the usual prevalence of a given disease within such an area or group.

A Dictionary of Epidemiology (5 ed.)

The constant occurrence of a disease, disorder, or noxious infectious agent in a geographic area or population group; it may also refer to the chronic high prevalence of a disease in such area or group.

A Dictionary of Epidemiology (6 ed.)

The word can be used to talk about an endemic area or an endemic disease.

Endemic may be used along with a defined threshold of disease – but doesn’t imply that the amount of disease will remain exactly the same from year to year, just that it isn’t exponentially changing as it would if in an epidemic state. Thresholds can vary by place, organisation and disease. See some threshold examples here. There seem to be a feeling that we need a decent amount of surveillance time to know whether a disease is capable of an endemic state.

Another example comes with a simple graphic to differentiate the different disease states…

Endemic is defined as the habitual presence of a disease within a given geographic area. It may also refer to the usual occurrence of a given disease within such an area (sometimes referred to as the “background rate of disease”)

Gordis epidemiology / by David D. Celentano and Moyses Szklo. (6th Ed. 2019)
The Dynamics of Disease Transmission. David D. Celentano and Moyses Szklo, Gordis Epidemiology, Chapter 2, 20-40.

Jekel’s epidemiology, biostatistics, preventive medicine, and public health (5th Edition; Joann G. Elmore, Dorothea M.G. Wild, Heidi D. Nelson, David L. Katz) says “When a disease in a population occurs regularly, and at a relatively constant level, it is said to be endemic, based on Greek roots meaning “within the population”” while Mayhall’s Hospital Epidemiology and Infection Prevention (5th Edition; David J. Weber & Thomas R. Talbot) defines it as “The usual level or presence of an agent or disease in a defined population during a given period. Clinical Epidemiology: The Essentials (6th Edition; Grant S Fletcher) says “When a disease such as iodine deficiency goiter or polio (after global efforts to eradicate it) is limited to certain places, the disease is called endemic”.

Some terms that tease out types of endemicity include…

Holoendemic disease

A disease for which a high prevalent level of infection begins early in life and affects most of the child population, leading to a state of equilibrium such that the adults in a population show evidence of the disease much less commonly than do the children. In many communities malaria is a holoendemic disease

A Dictionary of Epidemiology (6 ed.)

Hypoendemic disease

A disease that is constantly present at a low incidence or prevalence and affects a small proportion of individuals in the area. A term commonly used in malaria literature to refer to regions with low transmission.

A Dictionary of Epidemiology (6 ed.)

Hyperendemic disease

Disease that is constantly present at a high incidence and/or prevalence and affects most or all age groups equally

A Dictionary of Epidemiology (6 ed.)

And a couple of other definitions.

Incidence of disease

More generally, the number of new health-related events in a defined population within a specified period of time

A Dictionary of Epidemiology (6 ed.)

Prevalence of disease

A measure of disease occurrence.

A Dictionary of Epidemiology (6 ed.)

If not explained further, the term usually refers to the proportion (%, not rate unless time is involved) of individuals in a population who have the condition at a specified point in time (=point prevalence)

Others’ thoughts on endemicity

In a frustration-laden article from January, its author noted that some/many use ‘endemic’ interchangeably with ‘mild’. Here’s an example

People will still get infected. People might still get hospitalized, but the level would be so low that we don’t think about it all the time and it doesn’t influence what we do

Fauci says boosters for all key to U.S. reaching COVID-19 endemic level

The first takeaway from this article for me was this quote:

In other words, a disease can be endemic and both widespread and deadly

Aris Katzourakis, Nature 2022, Vol 601:458

If you are using endemic to mean milder disease, you’re misleading others, and you’re wrong. If you see it used that way, call it out. Words have meaning. I’ve also written a little about this before here.

The second really good takeaway from the Nature piece was this:

The same virus can cause endemic, epidemic or pandemic infections: it depends on the interplay of a population’s behaviour, demographic structure, susceptibility and immunity, plus whether viral variants emerge.

Aris Katzourakis, Nature 2022, Vol 601:458

My own frustrated version of this article would not be focussing on the ‘lazy optimism’ the author noted but on the utter departure of leadership as the real driver of a public belief that the pandemic is over, we’re back to normal, and things are fine. Those still at the frontline realise how ridiculous that is, but they no longer find support when they try and raise a flag about high hospitalisations and deaths, persistence, multisystem disease and long-term harms. “You’ve got a health budget, just stretch it a little and go make health”.🙄

So as with many things in biology, here’s a thing that’s complex trying to be described by a poorly-defined word. This isn’t really a simple ‘Yes’ or ‘No’ thing. We can’t easily generalise that ‘this is endemic’ or ‘this is not endemic’. But we can describe disease behaviours at a defined time and prescribed place using this term. I fell into this mistake, hence some reading and writing and consultation on social media to straighten out my knowledge.

‘Endemic’ is about the Disease

The word was intended to describe the behaviour of the disease and not necessarily an agent causing that. Of course, the two are linked, but there are subtleties to consider. But even the word ‘disease’ isn’t an open-and-shut thing.

Endemicity, influenza and influenza viruses

Let’s use influenza as a disease example. It’s caused by a range of different influenza viruses. Yes, plural. There are influenza A viruses like H1N1, H5N1, H3N2, H17N10, H7N9 (which now all belong to the species Alphainfluenzavirus influenza), influenza B viruses, influenza C viruses and influenza D viruses that can all cause human disease. But they don’t all co-occur. They are each affected by human behaviour, season, opportunity (for zoonosis), travel, other viruses (including new flu virus zoonoses leading to pandemics that can mess with existing virus patterns), immune pressure, vaccine match, vaccination uptake, imprinting and genetic change. But most people probably don’t really ‘look under the hood’ to see what’s causing flu – we just know it’s flu ‘season’.

There are periodic flu seasons caused by human-adapted influenza viruses) during which the number of cases rapidly rises above predetermined thresholds resulting in flu epidemics in temperate countries.

Flu (the disease) is endemic in between these periods, regardless of whichever flu is causing it. An epidemic is usually dominated by one influenza virus.

To add to the complexity, other viruses can cause similar flu-like illnesses, so we really need to limit flu disease discussions to influenza flu-virus-positive cases.

Seasonal influenza viruses cause asymptomatic, mild, moderate and severe infections inside or outside of their epidemic states. They don’t appear out of thin air or arise from the soil. The viruses rely heavily on travel to keep being introduced to temperate countries from other temperate countries and from the tropics. In tropical climates, flu can be found as an endemic disease; viruses continue to pass from person to person, continually evolving into new variants – some more ‘fit’ (they have a competitive edge), some the same fitness (although they may have changed in other ways) and some less fit than the ones that evolved from, all year round.

Influenza virus variants can completely replace prior variants of the same subtype. In those examples, the replaced variant is gone and so can’t be described as an ‘endemic virus’. But each is still a member of the same single viral species, Alphainfluenzavirus influenza viruses (fluA viruses). Travel disseminates them into new populations where they continue to evolve, leading to epidemics when a variant is suitably fit and the situation at the site is right.

While any specific seasonal influenza virus variant may not be endemic in temperate countries, the disease is. Flu ticks all the boxes!

Endemic diseases within a location can vary by year, region and season

In the example below from the Our World in Data Malaria page, we can see all sorts of presentations of an endemic disease in different locations.

Malaria is a universally agreed-upon example of an endemic disease caused by a vectorborne parasite that used to exhibit epidemic behaviour. It could again if controls suddenly failed or were prematurely eased, or if the vectors surged or populations moved suddenly.

Here we see another variable to consider in our story of the word ‘endemic’ – what causes diseases?

Influenza and SARS-CoV-2 spread effectively and just need breathing humans in a room. Malaria needs humans to be in proximity to competent and parasite-infected vectors. Ebola relies on the human touch to spread the virus.

What and how a disease is acquired can have an impact on how the state of a disease is defined. It might take fewer cases of a rare, high-consequence but slow-to-transmit pathogen to trigger a shift from an endemic to an epidemic state compared to a disease that can explode.

Malaria over time

When we look at one country over time – and allow for variability in testing and reporting of disease – an endemic disease is not always a straightforward straight line of disease whereby one person is infected at a time. Endemic disease can vary up and down in short quick steps because of infection clusters that are controlled or trend slowly up and down again in various ways yet still be an endemic disease.

SIDENOTE: it’s fantastic to see on this site and in the latest World Malaria Report, the hard work of so many malaria-endemic countries paying off as they get closer towards the goal of eliminating Malaria, a preventable and curable disease.

Similarly variable patterns, also affected by testing and reporting, can be seen with respiratory viruses when comparing countries – like flu-virus-positive flu hospitalisations below. Even after accounting for the northern versus southern hemisphere climate.

Malaria location can be limited within a country

Even within one country – see South Africa (map below) and Viet Nam for examples – some regions can exhibit higher levels of endemic activity than others.

A similar pattern can be seen during an influenza season – for example in Australia, the west coast can often demonstrate very different incidences to the east coast.

Malaria Risk Map from the Department of Health, South Africa’s Malaria site.

Malaria can vary over time in a single endemic region

There can also be disease variation that occurs within a year in a given country. One example is the effects of rainfall on the insect vectors of the Malaria parasite. In Viet Nam, the rainy season is when the highest risk of mosquito-human contact occurs in the highlands. This can lead to spiking case numbers.

Established viruses like influenza viruses and respiratory syncytial viruses, rhinoviruses, enteroviruses and metapneumoviruses are also known to circulate in seasonal patterns within a year, most likely due to changed human behaviours that bring us indoors to share exhaled infectious-virus-laden air particles.

Other endemic infectious diseases

Measles is caused by a virus, and the disease can be in an endemic state but then surge into epidemics when immunity wanes, new births rise, and vaccinations slip. Poliovirus, caused by a seasonal enterovirus was once a disease endemic to many locations, but vaccination and improved sanitation along with a huge effort have reduced its endemicity footprint to just a few regions of the world where vaccination has proven extremely hard to reach due to human factors.

Influenza is not endemic everywhere – the role of rapid travel

Australia and New Zealand (and others) saw the sudden cessation of an ongoing flu season and the maintenance of essentially no new flu cases until we opened our borders up. This wondrous outcome can be directly attributed to stopping travel which cut us off from the influenza distribution nodes of the US and China, and the local stay-at-home (lockdown) orders which snuffed out local transmission.

This surprised me as I had thought we’d see some internal transmission among the frontline workers and children at daycare who were still out and about. Other respiratory viruses did still tick along at reduced levels, however, but not influenza virus-positive influenza disease. And yes, Australia and New Zealand were still testing for influenza.

So while travel in the ancient days of epidemiology definitions might have been a tad slower and less multi-national than today, travel clearly plays a required role in the viruses that underpin some acute respiratory diseases.

Endemic can still mean lots of harm that we ignore

It’s also worth noting though – that despite a vaccine and antivirals and despite knowledge of how to reduce the risk of airborne virus infection such as that due to the influenza virus – every year we have seasonal flu epidemics with the resulting economic disruptions, cardiac harms, hospitalisations among the very young, and deaths predominantly among the elderly.

Even though stopping travel stopped the flu distribution network and reduced excess deaths, we have not – until this pandemic – ever made a half-decent effort to stop the harms due to seasonal flu. In decades. We’ve just learned to look the other way, read or ignored the annual articles about it causing harm to children and death to the elderly, shrugged if it starts little a earlier or later or peaks higher than before and we’ve done nothing more.

I guess this is what Fauci refers to when he says “the level would be so low that we don’t think about it all the time and it doesn’t influence what we do“. Except if we get avoidably sick or our cardiovascular or central nervous system is damaged such that we die early, or we get hospitalised (which comes with its own risks), or we or our loved ones die. We could do better, but we have managed to set a threshold of death that we are evidently happy with. And the same applies to many other diseases of course. So really, we just need that conversation to define what we will cheerily ignore when it comes to adding COVID-19 harms to this pile. Then we can get on with the business of life, and war, and abuse, without this latest disease influencing what we do.

Are we taking any actions to stop endemicity?

My simple question then, is why on earth does anyone expect an evolving, effectively transmitting airborne virus like SARS-CoV-2 not to hang around for many, many years to come and create a new massive disease burden? What is stopping COVID-19 from becoming endemic in many different countries? Perhaps even in more countries than flu currently is because of SARS-CoV-2 bounces between hemispheres. Or maybe it just hasn’t yet shown us its stable endemic reservoir, like the tropics for flu viruses. Or maybe we will eventually become too immune to it, and disease levels will drop right down. Maybe we aren’t at endemicity yet, or, as Prof Drosten says, maybe we are. Doesn’t really matter. What is being done to stop us from getting there at some point? I’m pretty sure it’s not the good intentions of people like me writing, ranting, meeting and interviewing about it when those who hold the power to make changes for good have, worldwide, decided to essentially ignore COVID-19 because …the public got bored?

With the vaccine pipeline now comparatively slower and our ability to distribute enough doses to all corners of the travel-linked earth being so poor, I can’t see how this COVID-19 won’t continue in its current state. If the world can build better vaccines and at the same time get its collective shit together around vaccine equity, maybe we can get somewhere then. 2024 maybe?

So are we in a pandemic or not?

Firstly – yes, we’re still in a pandemic. But we may also be seeing endemic behaviours, we just can’t be sure yet. There is no timeline we can refer to as the only other respiratory virus pandemics humans have lived through and have had modern science to help analyse is the flu – and it’s a virus the population already had some immune memory for. We’ll just have to watch this very different pandemic pathogen and look for the changes and patterns that I’m sure will emerge.

The disease (COVID-19) is still global and is still causing exponential case curves every handful of months. And each epidemic influences other countries through rapid travel. And some of those disease peaks are still very high.

Because of alllllll that, it’s better to say that COVID-19 is still in a pandemic state globally, and perhaps we can say that it’s in an epidemic state at the country level.

However – and only with the benefit of some undefined period of hindsight – it may be that the sort of case levels we see in the troughs above is the baseline we’ll eventually reach. Cases may stay at that high level, and it may only be the frequency of the epidemics that slow. But again, time will tell, and this is all guessing.

I still believe that COVID-19 peaks will slow to a regular cycle with one major peak per hemisphere per year. But I have no crystal ball, just what the poorly defined history of most of the other 200+ respiratory viruses shows us. In other words ‘COVID-19’ will at some time in the future become a seasonal disease whereby the most successful immune evasive causal variant wins out each year. It won’t ever be flu, but its epidemiology might one day behave like that of influenza (and many of those other seasonal viruses).

Yes, sadly we probably will still see the full spectrum of symptoms and diseases that make up the COVID-19 syndrome, including about a third who may go on to develop longCOVID/post-COVID conditions. Somewhat like we do for influenza which causes more than airway issues, affecting the cardiovascular and neurological systems as well as the lungs.

New SARS-CoV-2 variants may or may not also be different in other ways so some seasons’ epidemics will likely be more severe than others.

Perhaps SARS-CoV-2 will start to diverge into separate lineages, e.g. SARS-CoV-2 A and SARS-CoV-2 B and variants from one lineage may dominate in an epidemic one year while the other lineage dominates in the next year.

And those last few paragraphs will happen because leadership has ceased most measures in most places to prevent or even slow the spread of the virus that causes the disease. COVID-19 in 2022 (and earlier depending on where you look) got every opportunity to freely spread for three years. And yes, it is causing disease in the vaccinated population – we need better vaccines – but it’s also causing less death than it was thanks to those vaccines. That messaging was lost among the loud minority of anti-science, pro-disease merchants of chaos. But it remains bullshit.

We have failed to control COVID-19, so I don’t see elimination in any part of the world as a realistic outcome. Not fatalistic – just practical based on observations of what leadership has reduced in recent months:

  • It has reduced or made it harder to access quality testing in favour of a host of DIY options, some of which have terrible sensitivity but are still used for ridiculously important purposes.
  • It has reduced extra funding for some aspects of the response.
  • It has reduced data reporting frequency and messaging.
  • It hasn’t moved on air quality – one of the most important controlling responses we have yet to embrace.
  • It has removed or reduced employee supports.

If we don’t respond to the virus or try to reduce its spread and the death and harm it will keep causing, whether endemic or during epidemics, then it doesn’t really matter how we define its spread.

For now, we wait and see as we play yet another round of “what will COVID-19 be like this year?”.

So please get your boosters, wear a mask when there’s risk and advocate for filtered air at indoor sites where humans gather in groups. There are things you can do to keep yourself safe.

Welcome to 2023!

References

  1. A Dictionary of Epidemiology (5 ed.)
  2. A Dictionary of Epidemiology (5 ed.)
  3. COVID-19: endemic doesn’t mean harmless
    https://www.nature.com/articles/d41586-022-00155-x
  4. https://virologydownunder.com/an-influenza-virus-is-the-sum-of-its-parts/
  5. https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022
  6. https://www.health.gov.za/malaria/
  7. Endemic or epidemic? Measuring the endemicity index of diabetes
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287779/
  8. Endemic fatalism and why it will not resolve COVID-19
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841151/
  9. Top German virologist says COVID-19 pandemic is over
    https://www.dw.com/en/top-german-virologist-says-covid-19-pandemic-is-over/a-64214994
  10. Epidemic theory (effective & basic reproduction numbers, epidemic thresholds) & techniques for analysis of infectious disease data (construction & use of epidemic curves, generation numbers, exceptional reporting & identification of significant clusters)
    https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/epidemic-theory

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