Risk Factors for Severe COVID-19: What Makes It Harder for Some and Easier for Others?

risk factors severe covid-19The way it’s reported, you’d think that susceptibility to COVID-19 severity is equally distributed across the world’s population. But when you compare case and mortality rates between countries, differences emerge. There are even differences within countries and states and cities. It’s clear that other variables besides simple exposure to the virus and infection are at play. Research continues to emerge regarding risk factors for severe COVID-19.

What are they?

And, more importantly, can you modify any of the variables?

Does Blood Type Predict COVID-19 Severity?

Early on, researchers noticed an apparent association between blood type and coronavirus infection. Those with A or B-type blood were more likely to be positive; those with type O were less likely to carry the virus.1

Although the connection between blood type and infection risk has persisted, subsequent studies have failed to find any association between infection severity and blood type.

Verdict: Doesn’t appear to apply given current evidence. However, resistance to infection does confer a kind of protection against COVID-19 severity. If you’re not infected, you can’t develop any at all, let alone severe symptoms.

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Does Sex Determine Coronavirus Survival?

A meta-analysis of 12 studies performed in June 2020 found that males had a 31% higher risk of progressing to severe infection than females.2 All 12 studies analyzed had similar results; there was very little heterogeneity.

Is this caused by sex, though? After all, from what I could tell, the meta-analysis failed to control for other variables that might have differed between the groups, like metabolic syndrome or obesity. And yet sex does play a role, even when a risk factor like obesity is accounted for. Other research confirms that overweight men are at greater risk for coronavirus severity than overweight women, for example, and we know from previous research that men and women have different types of immune responses to viruses and vaccines.3

There may be a hormonal component to it, too. Estrogen therapy, for men and women, shows promise as a way to quiet inflammation (the source of coronavirus-related lung trouble) and improve survival rates.4

Verdict: Sex matters. Men are at greater risk.

Selenium Status and COVID-19

Early on, I noticed that selenium status plays a big role in susceptibility to a number of different viruses, including the flu, the original SARS, and many others. The viruses sequester selenium and utilize it to replicate and to weaken the host. Many of the original places where COVID-19 took hold had abysmal levels of soil selenium; this translates to lower levels of selenium in the food grown in the soil and a higher risk of population-wide selenium deficiency.5

Indeed, selenium status has now been implicated in COVID-19 severity. A recent study of COVID-19 patients measured the selenium statuses of those who survived and those who died. The surviving patients had much higher selenium levels.6

Verdict: Likely. This hasn’t been proven to be causal, but it’s certainly trending in that direction. It can’t hurt to eat a couple Brazil nuts every day.

Can Adequate Vitamin D Improve Coronavirus Outcomes?

The earliest coronavirus hot spots were actually colder, cloudier spots with low UV-indexes. Wuhan, China, had a ton of cloud cover in January and always has a lot of air pollution which further blocks the UV light. Lombardy, Italy, also had pollution problems and UV index too low to produce much vitamin D. And now, studies are finally coming out lending credence to the idea that vitamin D protects against severe infection.

In Iran, COVID-19 patients with vitamin D levels above 30 ng/ml had a lower risk of severe infection and death.7

In England, COVID-19 patients with higher vitamin D levels had a lower risk of hospitalization.8

It’s not just vitamin D, of course. Vitamin D is more likely a marker of sun exposure, which confers a multitude of other immune and health benefits. One such benefit with known links to COVID-19 is nitric oxide. Another is normalization of the circadian rhythm. So don’t assume mega-dosing vitamin D supplements will protect you from COVID-19 as much as getting natural sunlight will. Most of these people probably weren’t supplementing (or even thinking about) vitamin D at all. They went into the infection with the levels they had.

Verdict: Aim for 30 ng/mL and above. Get plenty of sunlight.

Does Obesity Make You More Susceptible?

Obesity is an enormous complicating variable. It’s not just because obese people are more likely to be unhealthy in other ways, although that’s probably part of it. It’s because obesity itself is unhealthy. Body fat secretes more inflammatory compounds and promotes an elevated baseline of inflammation. The coronavirus damages your body in part by up-regulating those inflammatory compounds. If you’re starting with elevated inflammation, you’re making the virus’ job that much easier.

Sure enough, obesity is linked to COVID-19 severity.9 More importantly, obesity is an independent predictor of COVID-19 severity. You can control for other variables like hypertension, diabetes, and heart disease, and the relationship persists.10 Extreme obesity (BMI of 45+) is even worse, with some research suggesting it quadruples the risk of severe COVID-19.11

Verdict: Obesity increases COVID-19 severity.

COVID-19, Diabetes, and High Blood Sugar

One recent study of 1200 Americans with COVID-19 found that those with diabetes or elevated blood sugar had a 29% mortality risk; those without diabetes or high blood sugar had just a 6% mortality risk.12 Among Chinese patients in another study, the mortality risk was 7.8% in those with diabetes and 2.7% in those without diabetes.13

Not only that, but diabetes and elevated blood sugar increases the risk of infection as well, so it’s a two-for.

Verdict: Diabetes and high blood sugar increase the risk of severe COVID-19.

Hypertension as a Risk Factor

Hypertension often rides along with obesity and diabetes, so you’d think it might be hard to disentangle it. But they’ve looked into this, and pre-existing hypertension may increase the risk of severe COVID-19 or death by 2.5-fold.14

However, those hypertension patients taking ACE inhibitors had a lower risk of severity or death than those hypertension patients who were not being treated.15 All is not lost.

Verdict: Hypertension increases the risk of severe COVID-19 outcomes, but ACE inhibitors mitigate this effect.

Previous Coronavirus Exposure

There are dozens of coronaviruses out there. The common cold stems from a type of coronavirus. The original SARS was a coronavirus, as was MERS. Animals carry coronaviruses (even our pets). And our immune systems are constantly reacting to them — even if we don’t get infected by a random coronavirus, our immune system is taking notes on and learning from it.

Perhaps that’s why T-cell immunity against other coronaviruses, like SARS, various animal coronaviruses, and perhaps even the common cold may work on COVID-19. This cross-immunity is long-lasting, too; even though SARS hit 17 years ago, many of the subjects in the study still had T-cell immunity against it.16 In another study, between 20-50% of unexposed people showed t-cell activity against COVID-19.17

Verdict: Although the details are being worked out (which coronaviruses confer some degree of immunity?) and I wouldn’t rely on this, previous coronavirus exposure seems to reduce severity.

Possible Connection to Omega-3 and Omega-6 Intake

This is speculative, but I’m confident that it will be borne out by the evidence.

Eicosanoids are inflammatory precursors—they mediate how we respond to immune insults, including inflammatory cytokines and pain responses. Eicosanoids come from the omega-3:omega=6 balance of our tissues. If we have a more omega-6-heavy tissue makeup, we will have more inflammatory eicosanoids. If we have more omega-3-heavy tissue, we will have more anti-inflammatory eicosanoids. It’s conceivable and probable that eicosanoid composition will determine COVID-19 response—and severity.18

Both dietary omega-3s and omega-6s have been shown to strongly influence tissue levels of omega-3 and omega-6 and thus inflammatory/anti-inflammatory eicosanoid balance. My guess is that seed oil-eating people with elevated tissue omega-6s are at a greater risk for severe COVID-19 than people with more balanced omega-6:omega-3 tissue levels.

Verdict: We’ll see.

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Fermented Cabbage Intake

Most of the countries with low COVID-19 mortality rates have a long tradition of eating fermented cabbage. There’s South Korea with kimchi and the Balkans and Central Europe with sauerkraut. And in a recent study, researchers found that fermented cabbage intake predicted low COVID-19 mortality.19

This is very preliminary and far from conclusive, but it makes sense. Fermented cabbage contains compounds that inhibit a vital receptor site through which the virus does much of its damage.

Verdict: Possible. Can’t hurt. Here’s an easy sauerkraut recipe if you want to cover your bases.

There are undoubtedly other factors that matter. Basic nutrient intake, the whole range of important vitamins and minerals we always discuss, yet-undiscovered genetic variants, macronutrient ratios, metabolic flexibility, gut health—all the things we know to affect other aspects of our health will probably play a role here, too.

But accounting for the factors I discussed today certainly won’t hurt and they may just help.

Thanks for reading, everyone. Take care!

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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