Guest Column: Evidence-based discussions need to occur

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MEEKER | “It is a capital mistake to theorize before you have all the evidence. It biases the judgment.”–Sherlock Holmes in Sir Arthur Conan Doyle’s A Study in Scarlet. This obligatory principle will guide our discussion; but instead of solving a murder case, we will be solving the case of our individual COVID risks. At the start of this pandemic, we had very little evidence to guide our decisions, however, we are now far enough into this epidemic that we can begin to make evidence-based decisions. As time passes, more evidence will emerge, and emerging evidence may even change the decisions we make based on the evidence now, at the end of 2020; but, by continuing to investigate, we can more accurately make decisions maximizing both protection for the vulnerable and a return to normalcy. As we begin examining evidence, let us refrain from preconceived conjectures, and instead follow the example in the world’s most famous fictional detective. After all, his famous attributes are founded on the surgeon who pioneered diagnosis by observation and the founding principles in forensic pathology — Dr. Joseph Bell. In our upcoming letters, our observations will examine evidence for the following questions: 1) What is my risk of severe illness or death? 2) What is my immunity status after a COVID infection? 3) What is my risk of adverse events from the COVID vaccine? You can then use this information to help solve your case of individual risk. You can use this information to empower yourself in lowering your personal risk. However, at the end of this process, it is still about risk. You can make decisions reducing your risk to 0.001% or lower, and you could still be unlucky enough to be 0.001%. Nothing in life is risk free. So now, without further ado, let’s dive in. If you do not care to read how we examine the evidence, are not a numbers person, or are only interested in the conclusions, please feel free to skip to the final paragraphs in each of the next letters. Today, we will begin with addressing the first question. What is my risk of severe illness or death? Let’s start with some background information. How do we determine fatality risk? In the purest sense, we take the total confirmed deaths by COVID, divide it by the total confirmed COVID cases, then multiply it by 100. This provides the infection fatality rate (IFR) as a percentile. However, attaining this figure is not quite that simple, and endeavoring to nail down the exact IFR has been extremely difficult for multiple reasons. First, up to 40% or more of individuals with COVID have no symptoms, and therefore never seek medical testing. Second, another large majority have very mild symptoms that are mistaken for another illness, consequently this group also does not seek a medical diagnosis. Thirdly, the false negative rate has ranged from 10% to 30% depending on the study; this means 10% to 30% of individuals who actually have COVID get a test result falsely saying they do not have COVID. And finally, there are many who suspect they have it (and likely do), but choose to not get tested and simply quarantine themselves. For these reasons, the confirmed positive cases significantly underestimate the true number of cases; and, indeed, 22 seroprevalence studies (studies examining the presence of antibodies to the virus, indicating past infection), suggest the true number of cases is likely 10 to 20 times higher than the confirmed number of cases, as 10 to 20 individuals have had it without a confirming test for every 1 person who has had a confirmatory test. This statistic has also been confirmed by the CDC, and another large study (described below) also confirms this to be the case. Using this information to determine the IFR provides a broad number including all ages and risk factors. After determining this global IFR, we will then break it down by age to help us solve this case of risk more individually.

So, let’s look at the global number first, then we will break it down. Google is not always the recommended place to obtain your medical advice, but it will serve our discussion well. As of 12/27/2020 (date of this writing), Googling “covid by state” and adjusting the “cases” tab to reflect “worldwide” data provides the following information: 1.76 million confirmed COVID deaths and 80.5 million confirmed COVID cases. Using the formula above, this gives a worldwide IFR of 2.1%. Changing the tab to reflect the United States, the IFR is calculated to 1.7%. Narrowing further to our home state of Colorado, the IFR is calculated to 1.4%. Next, we have to consider the evidence of underestimated caseload as described above. If we use evidence from the seroprevalence studies and the CDC, this would indicate the confirmed COVID cases are likely 10 to 20 times higher. If we estimate on the low side and increase the caseload by only 10, the IFR’s come out to be 0.21%, 0.17%, and 0.14% for the world, United States, and Colorado, respectively. What does this mean? For comparison the global death rate for influenza ranges from 0.08% to 0.15% depending on the year. This is great news, as we initially thought COVID’s IFR was up to 10 times higher than influenza, and as more data emerges, it looks to be inching closer to the IFR for influenza. However, before we take too much comfort in this, we also must consider that COVID is significantly more contagious than influenza. Consequently, many more people will contract COVID than influenza, and this mathematically means COVID will kill more people than influenza, even if we eventually determine COVID to equal influenza in IFR. Broadly speaking, your risk of severe illness or death if you contract COVID may be much closer to influenza than initially thought (great news), but the total number of lives COVID will claim will still be higher than influenza due to its increased infectivity compared to influenza (not so great news).

Next, let’s narrow down IFR by age and risk factors. Multiple analyses have determined the greatest risk factors for severe illness and death, separate from age, include diabetes, high blood pressure, chronic obstructive pulmonary disease, smoking, cardiovascular disease, and obesity. To account for age, let’s turn to a study published in November of 2020 examining IFR by age across 45 different countries using the 22 seroprevalence studies referenced above to aid in conclusions. This study found a strong consistency in death rate by age across the 45 countries up to the age of 65. Above 65 years, significant variability was found secondary to nursing home populations. When nursing home populations were accounted for, the consistency returned, showing vulnerability does increase with age, and our most vulnerable do indeed live in nursing homes. This makes sense when you return to the original list of risk factors, because the risk of attaining these risk factors increases with age, and the nursing home contains the highest proportion of individuals with these risk factors. This begs the question, is the true risk your age, is it the overall condition of your health, or is it both? The answer likely includes both, with a heavier emphasis on your overall health, as studies from Italy suggest 1% to 5% of people who died had none of the above risk factors, meaning 95% to 99% of people who died had at least one risk factor other than age. Statistics from England also suggest your health is a stronger indicator of risk than your age, as 95% of those who have died in England also had at least one risk factor, per the most recently published data on Dec. 17, 2020.

Specifically addressing age, here is the approximate IFR breakdown by age from the study of 45 countries:
■ 0-4 years old = 0.0009% to 0.001%
■ 5-19 years old 0.0003% to 0.008%
■ 20-29 years old = 0.0011% to 0.015%
■ 30-39 years old = 0.008% to 0.1%
■ 40-49 years old = 0.1% to 0.12%
■ 50-59 years old = 0.08% to 0.17%
■ 60-69 years old = 0.09% to 1.2%
■ 70-79 years old = 0.15% to 9%
■ Greater than 80 years old = 2% to 10%

This leaves us to address one more piece of evidence before concluding this letter. If I am an adult living in a home with a school-aged family member who contracts COVID, is my risk acquiring COVID higher, and is my risk of severe illness or death higher? To the first part, yes, your risk of acquiring COVID is higher; living with someone who has COVID has been established as one of the highest risk factors for acquiring COVID. To the second part, no, according to a study of more than 9 million people in England, your risk of severe illness or death from COVID is not any higher in this scenario.

In summary, the global infection fatality rate, including all ages and risk factors, appears to be inching closer to influenza, and it is much lower than we initially thought. However, COVID is still much more contagious than influenza and consequently will infect a larger number of people, meaning COVID will still claim more lives, even if the infection fatality rate is eventually found to equal influenza. Your individual risk can better be determined by considering the findings in the study described above, combined with your known risk factors. If you are high school or early college age in excellent health, your individual risk of death is as low as 0.0003%. However, if you are 80 years old and have at least one risk factor, your fatality risk could be as high as 10%. The greatest indicator of your risk appears to be the state of your health.

In our next letter, we will examine evidence regarding immunity, risk for reinfection, true second infections, and we will weigh risks and benefits concerning the COVID vaccine (the vaccine, like all medical treatments, is not entirely risk-free). If you are uncertain about the vaccine, stay tuned for our next letter. In the meantime, maximize your health to lower your own risk. Plan, cook, and prepare your meals; fill your grocery cart with fresh produce and avoid sugar, soft drinks, juice, and processed foods; stop smoking; exercise; practice proper sleep hygiene; and take your metabolic and cardiovascular health seriously. Hand washing, social distancing, and mask wearing may slow spread, but these actions alone will not significantly decrease your individual fatality risk should you contract the virus. You have the power to decrease your risk of death from all causes, including COVID. Avoid headline evidence and expert opinions, as COVID has not been around long enough to have any true experts on the subject. Examine the evidence for yourself, empower yourself, make healthy decisions, and help us return to normalcy while protecting our most vulnerable

REFERENCES
■ “Age-specific mortality and immunity patterns of SARS-CoV-2.” Megan O’Driscoll, et al. Nature. November 2020.
■ “Association between living with children and outcomes from COVID-19: an OpenSAFELY cohort study of 12 million adults in England.” Harriet Forbes, PhD, et al. British Medical Journal. November 2020.
■ Center for Disease Control – multiple articles
■ “Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on December 16th, 2020.” Italian National Institute of Health.
■ “Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on March 17th, 2020.” Italian National Institute of Health.
■ Data tracking by “ Wikipedia, government health ministries, The New York Times, and other authoritative sources, as attributed.”
■ “Deaths from COVID-19 with no underlying health conditions, broken down by age.” United Kingdom Office for National Health Statistics. December 2020.


By Pioneers Medical Center Providers – Special to the Herald Times