The confusion over “flu”: CFR, IFR and all-cause pneumonia
Two things that have bothered me on both ends of the faulty flu vs Covid comparisons from the start of the pandemic and throughout has been 1) Covid CFRs reported as though they are IFRs unadjusted for comorbidity risk and age, and 2) false and inflated CFRs for influenza. I’d like to try to clear both of those up here. To start on the Covid end, a team of researchers at Stanford University recently published a study estimating the global median infection-fatality rates by age groups in the non-elderly population based on national seroprevalence data, further accounting for seroreversion (loss of antibodies over time in previously infected individuals). Such seroprevalence data is the only way to really determine IFRs. Otherwise, reported cases, even if they are communicated as IFRs, are actually CFRs which aren’t particularly helpful to the every day person in determining risk. The median rates calculated in their review would be higher for those with underlying comorbidities and lower for those without during a time period of a more virulent circulating strain and no immunity to protect from severe disease from either prior infection or vaccination as is currently the case. “These estimates” they write, “provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.” Based on that background, the median IFRs in the Stanford review of immunologically naïve populations for non-elderly age groups (<70) were as follows:
0–19: 3 in 1,000,000; 1 in 333,333
20–29: 1 in 33,333
30–39: 1 in 10,000
40–49: 1 in 2,857
50–59: 1 in 775
60–69: 1 in 200
Adjusted IFRs for less virulent strains in immunologically naïve populations without prior infection or vaccination (a small population at this point) might be as follows:
0–19: 1–1.5 per million
20–29: 1 in 66,666
30–39: 1 in 20,000
40–49: 1 in 5,714
50–59: 1 in 1,550
60–69: 1 in 400
By comparison, according to a 2010 Cochrane review on influenza and influenza vaccination, 1–4% of the adult population have influenza-like symptoms each year. Out of an adult population of 254 million, that equates to 3–11 million cases annually. A more recent updated 2018 Cochrane metareview estimates ILI rates between 1–2%, so 3–6 million symptomatic cases in adults annually. The U.S. CDC, however, reports higher estimates — 9,000,000–40,000,000 million symptomatic annual cases, which despite including children are still overestimates compared to international estimates. Even though lab-confirmed influenza itself only makes up a small proportion of all-cause deaths in the U.S. (1,000–2000 annually), and only a fraction (10%) of ILI is caused by influenza, and only a small proportion of all-cause pneumonia deaths are associated with influenza, the CDC reports all-cause pneumonia and influenza deaths as one category. This conflation is done, some argue, to market disease for the sake of encouraging increased influenza vaccination uptake. Indeed, at a 2004 workshop for the Institute of Medicine, the CDC revealed a PowerPoint for increasing vaccine uptake entitled “‘Recipe for Fostering Public Interest and High Vaccine Demand,” which explicitly explained the necessity of creating concern, anxiety, worry and the perception of vulnerability even in typically low-risk groups in collaboration with media to increase uptake of influenza vaccines. Hence, one can presume, the reason for the conflation.
Using CDC’s overestimates (compared to international reviews) for estimated symptomatic ILI, the actual CFR for the hundreds of bacteria, viruses, fungi and unknown etiological agents that cause all-cause pneumonia is technically as Dr. Fauci reported in the New England Journal of Medicine 1 in 1,000. However, this is a grouping together of many etiological agents with a reported CFR that applies exclusively to the elderly — meaning, besides the conflation with many causes, the CFR for “flu” is not age-adjusted. IFRs accounting for asymptomatic carriage would be lower. I don’t know of any age-adjusted studies that have used seroprevalence surveys to determined the IFR of influenza itself. However, a report by the American Lung Association based on CDC data from 2000–2013 does estimate the mortality rate from influenza teased out from all-cause pneumonia. Note that the definition of mortality rate is not the IFR, but rather the total number of people in an age group divided by the total number of deaths from influenza in a given year. Even though the population mortality rate is not the same and will be lower than the actual IFR, because Covid is more infectious and the entire population was immunologically naïve to start, the population mortality rate was a good proxy during the first year of the pandemic for how people actually gauge annual risk. For each age group, the American Lung Association reported the population mortality rate from influenza as follows, which as with Covid, also needs to be adjusted for individualized risk according to underlying health status:
Under 5s: 3 in 1,000,000; 1 in 333,333
5–14: 1 in 1,000,000
15–44: 1–2 in 1,000,000
45–64: 1–6 in 1,000,000
Vs. Mortality rate from all-cause pneumonia in the non-elderly population:
Under 5s: 1 in 100,000
5–14: 2 in 1,000,000; 1 in 500,000
15–44: 1 in 100,000
45–64: 7.7 in 100,000; 1 in 13,000
The mortality rate of lab-confirmed influenza proper, which is how non-elderly age groups gauge annual “flu” risk, is not as stated by Dr. Anthony Fauci or at least in the terminology subsequently cited by the media 0.1% (1 in 1,000), not even when the estimates are conflated with all-cause pneumonia for non-elderly age groups. You can see why public confusion over an inflated “flu” mortality rate of 0.1% without distinction between CFR, IFR and mortality rate and without age adjustment could mislead anyone in the 60 and below age range familiar with seroprevalence-based Covid IFRs into thinking Covid was no worse than a “bad flu.” Indeed, many referenced Dr. Fauci’s publication in the New England Journal of Medicine — “This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%),” to support this line of thinking. Publicly, Fauci stated and media reported a mortality rate. In published scientific journals he referenced a case fatality rate for what is functionally all-cause pneumonia, not influenza. This misunderstanding and confusing/conflicting use of terms on multiple levels from both health officials and media led many to underestimate the risk of Covid for their age group, which was a pretty unfortunate miscalculation, especially if the miscalculation was made by someone with underlying health conditions, (especially obesity). Many even now reference the Stanford study on Covid IFRs as evidence that Covid was never any worse for most age groups than “a bad flu” (e.g. even less than 0.1% — 1 in 1,000), but now they are comparing age-adjusted Covid IFRs to all-cause pneumonia CFRs almost entirely driven by the elderly age group. None of this originated from conspiracy, but rather directly from decades of misleading public health messaging on the virulence of “flu” and unhelpful confusion and lack of clarity over terminology used to describe mortality, replicating the same confusing and mixed messaging initially regarding masks. How unfortunate!
On the other end of the spectrum, reporting CFRs instead of IFRs, and lack of adjustment for comorbidities which are substantive, has terrorized many healthy young people well beyond a rational adjudication of risk for their age group — also unfortunate! The IFR of Covid for 0–19 year-olds in an immunologically naïve population is comparable to the population mortality rate from influenza, which suggests that the IFR of influenza in this age group is actually worse (e.g. up to 20% infection rate in children with influenza annually yields a population mortality rate comparable to what 100% of the population infected with Covid in this age group would). A further difference being that with influenza 100% of primary infections in the immunologically naïve population (under 5s) happens over a period of 5 years, while with Covid nearly 100% of first exposures happened for the entire age span of 0–19 over a period of 1–2 years.
This is about the only group where the influenza vs Covid comparison was actually applicable from the very beginning. Although experiences obviously vary and some have worse outcomes, it does track with personal experience with our kids at home relative to their own health histories. Our twin 6 year-olds, one of whom typically struggles and gets hit hard with seasonal respiratory viruses each year and who we worried over the most, both had one afternoon of a very low-grade fever and a barely perceptible one-day cough for the extent of their experiences with Covid. If it had been a non-pandemic year, we wouldn’t have blinked or thought to test for anything. Once they ‘recovered’ we were very much put at ease for how they would handle any future encounters.
Dr. Thomas Jefferson, Oxford professor and decades-long scientific reviewer for the Cochrane Collaboration who co-authors a blog with Dr. Carl Hennigan, the Director of The Oxford Centre for Evidenced-Based Research, confirms the Stanford IFRs for younger age groups in their own research.
“There are further problems with the IFR to consider. First, it assumes all deaths with a PCR positive test or Covid on the death certificate were caused by SARs-CoV-2. This is not the case, as we have shown. The IFR also doesn’t account for hospital deaths or the complex interaction of multimorbidity and the assignment of causation.
An analysis distinguishing causation in under 18s, as opposed to those who died of another cause but were coincidentally infected, reported a mortality rate in < 18-year-olds of two per million — an IFR of 0.0002%. Suggesting Covid is the underlying cause of death in only about a quarter of young people when it is registered on the death certificate.”
In comparing Stanford’s and their own estimates to the Imperial College’s which initially informed global policy they write:
“The consequences of overestimating the IFR are profound. It overpredicts the number of deaths and influences political decision-making without considering the long-term harm and well-being effects.”
These harms also include the adverse events from vaccination itself that young people were told to put their lives on hold to wait for, and whose educational and job prospects were put in jeopardy if they refused, even if they had already recovered from Covid. The rate of life-threatening reactions from anaphylaxis in a prospective study utilizing active surveillance of the first dose of the primary series was 1 in 4,000 with 2% experiencing acute allergic reactions (hives, swelling, wheezing or respiratory distress). RCTs that dropped data of a number of life-altering AEs from the trial and screened out people with allergic sensitivities prior to the study estimated an excess rate of severe adverse events (SAEs) over placebo of 1 in 800 in adult trials where SAE was defined as “an adverse event that results in any of the following conditions: death; life-threatening at the time of the event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; medically important event, based on medical judgment.” Post-marketing studies estimate a higher SAE rate of 1 in 200 for autoimmune patients, an increasingly common health condition in younger generations, of which 1 in 10 sought medical care that required treatment post-vaccination. Hopefully this helps Americans who have been bombarded with confusing and mixed messaging about both “flu” and Covid over the years to better understand many European nations’ more recent decisions regarding boosters and even the primary series for healthy young people lacking severe comorbidities, especially in the context of high levels of immunity from prior infection. Hopefully this also helps shed some light on why some countries never made the recommendation to healthy children at all.
One Million Dots — whether for Covid or influenza, a visual for parents to help calm the U.S. media amygdala triggered brain (speaking from experience!)
Dr. Syed Mobeen MD reviews Nov 2022 Qatar study on VE in children 5–17 in the context of Omicron —
