What if the Flu isn’t “just the Flu?”
The true death toll of flu points to the vast challenges of endemic Covid.
As the omicron variant gains traction throughout the world, there are still a lot of questions about what is causing it to spread so quickly, if and how much it can evade vaccine-induced-immunity, or if it will result in similar levels of disease as past variants.
While these questions remain, it is becoming clearer that Covid is a longer term problem, and so it makes sense to start thinking about what “endemic” Covid could look like. Since flu and other respiratory viruses like Covid spread through the air, endemic flu is a natural place to start.
After seeing just how much more deadly Covid is than flu, and looking more closely at the true mortality toll of seasonal influenza, I believe that the picture most have in their heads of what the end of pandemic Covid may be unrealistic and counterproductive.
Because while we are investing heavily in vaccination, the sense that the pandemic is going to “end” at some point in the not-to-distant future is leading to an underinvestment in other structural solutions we are going to need - a revolution in filtration and ventilation so that buildings do not readily spread disease and free, readily-available rapid testing to make gatherings safer.
The sense seems to be that endemic Covid will look something like the flu, but we know that Covid is currently much more deadly than flu, so is there any good reason to believe this to be the case?
And further, what people do not realize is that the flu is actually much more deadly than the estimates of flu deaths suggest.
Seasonal flu may kill 90,000 or more people per year in the United States - nearly three times the estimates of flu deaths.
Realizing this came as a bit of a shock to me, because before Covid I really hadn’t given that much though to flu, and never personally had a particularly bad case.
Let’s start by looking at the official estimates for flu deaths.
In the early days of the Covid-19 pandemic, it was common for those inclined to minimize the threat the disease posed by saying it was “just the flu” or something similar. Now that tens of millions of people have died globally, these comparisons are rarer, but they were always inappropriate, and not just because they were dismissive of the overwhelming mortality of Covid.
Because endemic flu is really bad, and it kills a lot of people.
Using CDC estimates above, seasonal flu kills 6 to 7 times more than the deadliest battle in the Civil War and more than 10x more than died on 9/11.
Dismissing Covid as “just as deadly as all car accidents” is uncharitable even if Covid were only that bad. 40,000 Americans is still a lot of people. But it’s probably a lot more than that.
If flu kills more people, why don’t we know it?
Given fairly robust cause-of-death reporting in the United States, it’s a fair to question the idea that flu might be more deadly simply because we would know about it if it were. If flu were really that bad, we would know surely know about it, right?
Before we look at the evidence that flu is more deadly than commonly understood, there are a few key reasons that we might not be able to see flu deaths that are actually happening.
Reason 1: Flu is “in the air we breathe”
While there is ample evidence that flu spreads, like Covid-19, through the air, that is not the issue here. Flu is just with us, everywhere, every year, and the seasonality of flu mirrors normal seasonal mortality trends. See the average number of deaths per day in the US.
Flu deaths follow roughly the same pattern. More people die in the Winter, and more people die of flu in the Winter.
Unlike Covid, which can be compared to past baselines, real flu deaths are a part of the baseline.
Reason 2: Flu deaths are estimated
From the outset, we should be clear that the number of deaths from influenza both in the United States and globally, is estimated. In 2018, we only conducted between 35 and 40 million flu tests in the entire US. That is a large number in some sense, but it’s fewer than 1/10th of the number of officially reported Covid tests that have been conducted through October 2021, to say nothing of the number of rapid tests that have been done off the books.
Despite hundreds of millions of tests, we are still missing lots of Covid deaths - according to The Economist’s most recent estimate, nearly 3 out of 4 deaths from Covid globally.
The picture is better in OECD countries but as economist from the University of Central Arkansas, Jeremy Horpedahl, has shown, we’re still missing nearly 1/3rd of Covid deaths in the United States, even though it’s the number one economic and medical priority in the country.
If, despite the fact that we are focusing so heavily on identifying and treating Covid that we are still missing so many excess deaths, then it seems reasonable that a disease which we largely ignore could hide in plain sight.
What’s the evidence that it’s flu that is killing people?
There is a lot of it actually. We typically think of flu as a respiratory illness, and we are good at surveilling for flu like illness, but our surveillance is predicated on looking for disease that looks like flu. Indeed the CDC’s ILInet looks for “influenza like illness” and specifically for “respiratory illness that included fever plus a cough or sore throat, also referred to as ILI.” Are we missing these? Probably not in significant number.
It’s the secondary deaths - those that are triggered by influenza - that we aren’t so much missing as we are failing to associate with flu.
People are simply much more likely to die after they get the flu. These aren’t counted as flu deaths, but if we tested like we do with Covid, they might very well be. Let’s walk through some evidence that this is the case.
Getting the Flu Vaccine reduces your risk of heart attack and stroke
This is not common knowledge, but multiple studies have confirmed it.
A JAMA study in 2013 of 6,700 people enrolled in clinical trials, for example, found that “those who had been vaccinated against the flu had a 36% lower risk of a having major cardiac event during the following year. And for those who had recently had a heart attack, a flu shot cut the risk of heart attack or stroke even further”
Many of those enrolled were at higher risk for heart disease, but 36% is an enormous reduction. Another study, this one a meta-analysis, showed a large benefit across studies, strongly favoring flu vaccination.
The American Heart Association highlighted the 2020 study, noting that the benefit of a single flu shot offered similar benefit to taking beta blockers every day for a year. It’s just astonishing, all the more so because if you talk to your cardiologist, there’s a good chance they will have no idea that this is the case.
The meta-analysis of 16 randomized and observational studies covered the experiences of more than 237,000 people. It concluded those with heart disease who were vaccinated for the flu were 18% less likely to die from heart problems and 28% less likely to die from any cause. They also were 13% less likely to experience any type of major heart problem than those who didn't get a flu shot.
"Compare that to beta blockers and ACE inhibitors, which are used to control high blood pressure. They reduce mortality by 20-25%," said lead investigator Dr. Siva Yedlapati, an internist with Erie County Medical Center in Buffalo, New York. "This is totally compatible with that number, and it's just one shot per year, compared to taking medications every single day for the whole year. This is a huge benefit."
This 2018 study showed that patients who were hospitalized for heart attack were 6 times more likely to have had been infected with flu within a week of having been hospitalized. In essence, much of the risk of increased heart events from those who had the flu came within that week, suggesting that the benefit is based on preventing severe flu.
Houston Methodist hospital recently noted another study where “patients admitted to the hospital with acute coronary syndrome were randomly assigned to either receive a flu vaccine or not before discharge. Major cardiovascular events occurred less frequently in the vaccine group than the control group (9.5% vs. 19%).”
Another study of around 50,000 older adults in Ontario over several flu seasons suggests that the flu vaccine reduces all-cause mortality in people who contract the flu by 20-34%.
Flu spikes appear to have secondary effects that are observable at scale. While flu deaths are tiny relative to heart disease, you can see peaks in heart disease and flu in both magnitude and timing. The 2017-18 flu season which was about twice as large as an average flu year, stands out as an unusually large year not just for heat disease, but also for cancer and several other significant causes of death.
This is not to say that flu is the actual cause of all these deaths, but that a lot of deaths that don’t get coded as influenza are nonetheless the result of flu infections.
Flu triggered deaths are under-studied
Just how many deaths flu actually triggers has not been studied as much as you might think. A 2004 study looked at the relationship between infection and heart attack (myocardial infarction or MI) and found that official flu deaths, then estimated at 22,000, were significantly undercounting flu-triggered deaths:
”…the influenza-related death toll may be even higher: because influenza is not a recognized trigger of MI, it is very unlikely to be recorded on the death certificates of patients who die of MI, stroke, heart failure, or cardiac arrest. Consequently, the number of deaths triggered by influenza is under-recorded. In fact, our estimates—derived from clinical trials and case-control studies—show that, by triggering cardiovascular events, influenza may cause up to 90,000 deaths per year.”
A clever study from Charlotte Warren-Gash looked at the differences between flu seasonality in the temperate climates of England and Wales and the subtropical climate in Hong Kong to observe differences in heart attack death patterns. A summary of the study notes a “strong association between population levels of influenza and AMI hospitalizations and deaths in both temperate and subtropical climates”
The authors estimate around 3-3.5% of heart attack deaths are caused by flu in England and Wales, and 4-6% in Hong Kong.
5% of heart disease deaths in the US would be about 30,000 additional deaths, which be a roughy doubling of the current estimate of flu deaths.
Inflammation is the key mechanism
Scientific American did an explainer on “How the flu actually kills people” that has a great breakdown of the body’s response to infection:
“The overwhelming viral hoard triggers a strong response from the immune system, which sends battalions of white blood cells, antibodies and inflammatory molecules to eliminate the threat. T cells attack and destroy tissue harboring the virus, particularly in the respiratory tract and lungs where the virus tends to take hold. In most healthy adults this process works, and they recover within days or weeks. But sometimes the immune system's reaction is too strong, destroying so much tissue in the lungs that they can no longer deliver enough oxygen to the blood, resulting in hypoxia and death.”
The body is vulnerable to secondary infections and pneumonia, like it is with Covid, but the immune inflammatory response affects the vascular system as well. "Flu can make a cholesterol filled plaque vulnerable to rupture, form a blood clot and cause heart attacks and sudden death," says Venkat Pasnoori, MD, in the Houston Baptist piece linked above.
Just how this happens is still being understood, but it’s known that both flu and Covid induce inflammatory response, and with both diseases this inflammatory phase can be very difficult on patients, particularly ones with co-morbidities.
What does this mean for endemic Covid?
Aside from vaccination, we do very little to curb the spread of flu and it shows. We may see 100,000 deaths from the flu in the US as a result of our current approach, but we largely don’t notice it because it’s always been that way.
When people talk about Covid becoming endemic or declare “the pandemic is over” there seems to be an implicit assumption that mortality from Covid will recede to a background level that’s hardly noticeable while people just move on.
If all “endemic" Covid did was to add the equivalent of another flu season on top of our current burden, it will be a huge burden on a hospital system that’s struggling to maintain staff. If on the other hand the much higher relative mortality of Covid versus the flu persists, then the US could be looking several hundreds of thousands of annual deaths from the disease.
Therapeutics will help, and vaccines will likely improve, but as large percentages of the population remain resistant to vaccination, and immunity from past infection wanes, we could continue to see one (or perhaps two) seasonal waves of Covid every year while tens of millions of Americans are vulnerable to serious disease. If we allow Covid to circulate at high levels in the US, we are inviting correspondingly large death tolls year after year.
This a long term problem. We need to fix our buildings and need to recognize that rapid testing is going to be a part of life going forward.
We are dealing with a novel disease, so perhaps we’ll receive a pleasant surprise at some point. But as we see the beginnings of another large Winter wave in the US, it is time to recognize that Covid, like the flu before it, is a long-term problem that will require large, systemic, and permanent changes how we operate.
This needn't mean that we exist in a state of withdrawal, but rather that we invest in the tools that we know will allow us to keep circulation low without burdening individuals to protect themselves.
Covid is an airborne disease that primarily spreads indoors, so we should invest in making indoor air less amenable to transmission. Putting HEPA filters or good ventilation in every public place could do a lot to eliminate superspreading, for example, and sub $1 rapid tests would allow people to gather safely with friends, family and work gatherings. Masks are highly effective and good quality, highly breathable masks are easy to wear in high risk areas. None of these solutions is perfect, but they are a huge improvement on the free-for-all we’re living through now.
Endemic flu is a warning.
We can continue to pretend that the pandemic is almost over, or we can look to the incredibly harmful effects of the flu and recognize the need to invest the infrastructure to see the benefits of more effective disease suppression going forward. Let’s listen to the warning and invest in our collective health.