Is Age NOT a Risk Factor for COVID-19?

Whenever COVID-19 deaths are plotted by age group, a similar picture emerges, as in this graph for Massachusetts:

It's mostly the older people who are dying. In Massachusetts, the chances of dying of COVID-19 for anyone 80 years or older is about a thousand-fold higher that for anyone aged 20-29. Different regions may show somewhat different numbers, but the overall picture is always the same: the risk of dying from COVID-19 appears to increases with age.

But is age alone really a risk factor for dying from COVID-19? Given graphs like the one above, that almost seems like a crazy question - but it is not. The first hint comes from looking at other health problem of patients who died of COVID-19 had - here is the graph for Massachusetts:

More than 98% of those who died had other health problems like cardiovascular disease, diabetes, hypertension, and so on. Of course, there is a link between age and "underlying conditions" (often called "comorbidities"). But what is really causing more severe COVID-19 outcomes and deaths - age, underlying conditions, or both?

One interesting study that looked at 7,029 COVID-19 cases in adults at least 60 years old looked at exactly this question. The authors concluded:

Age was not a predictor of COVID-19 severity in individuals without comorbidities and structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age.

This conclusion was based on modeling the effects of multiple different risk factors, which included various underlying conditions, the number of hospital beds in a community, and "social lag" indexes, "which is a composite of several factors which are measured to estimate social disadvantage and structural inequality based on population census data".

One of the risk factors that the study identified was obesity, which "remained as a significant predictor of mortality even in individuals without other comorbidities"; obesity increased the risk of hospitalization by 70%, and the fatality risk by 37%.  However, obesity does not show a significant increase with age: when looking at a given population, the percentage of obese young people is very similar to the percentage of obese older people. Something does not seem to quite match here!

A study from the Charité university hospital in Berlin helps to understand what is going on.  It looked at 30 COVID-19 patients, and measured their "visceral fat area" with CT scans. Basically, "visceral fat" is belly fat, as opposed to subcutaneous ("under the skin") fat. Visceral fat has been linked to diabetes, cardiovascular disease, and immune system disorders. It generates cytokines, and one of the primary ways to die from COVID-19 is through the effects of a "cytokine storm". The Charité study reports:

An increase in visceral fat area (VFA) by one square decimeter was associated with a 22.53-fold increased risk for ICU treatment and a 16.11-fold increased risk for mechanical ventilation (adjusted for age and sex). 

We'll look at what an increase of "one square decimeter" means below, but take note of the very large risk factors: 22-fold and 16-fold higher risk! A simpler measure that the study also took was the "upper abdominal circumference" - roughly speaking, measuring the waist circumference. They report that each additional centimeter increases the risk of ICU treatment by a factor of 1.13, and the risk of ventilation by a factor of 1.25. The numbers are more impressive if we use inches: one extra inch increases the ICU risk by a factor of 1.36, and the risk of ventilation by a factor of 1.76.

The next thing to look at is how visceral fat increases with age. A study from 2010 shows this graph:

Between the age of 20-29 and 60-69, the amount of visceral fat increases by almost 100 square centimeters - that's one square decimeter. With respect to COVID-19, this increase corresponds to a 22-fold higher risk of ICU treatment in the Charité study.

The study explains that increase in visceral fat with age is linked to weight gain, muscle loss, and re-distribution of fat from arms, legs, and face to a "more central fat deposition".  We know that exercise and physical activity can reduce or prevent weight gain and muscle loss, but it also affects the re-distribution of weight. In other words, exercise and staying active can substantially reduce the age-related increase of visceral fat.

The "typical" development as we get older is that we get less physically active and gain weight. That increases visceral fat, which promotes low-level inflammation and increases the likelihood of multiple diseases, including high blood pressure, cardiovascular disease, diabetes, and others. Each of these diseases itself is a risk factor that can lead to more severe COVID-19 outcomes. As an older person suffers from multiple diseases, independent living can become impossible; the person needs to move to a nursing home or similar long-term care facility. When COVID-19 infections reach a nursing home, the inhabitants are at an extremely high risk of severe disease and death due to the multiple "underlying conditions". This is only exasperated by less time spent outdoor, and the  vitamin D  deficiency that is likely to develop as a result, which has also been linked to more severe COVID-19 outcomes.

Fortunately, the conclusion from the studies I described above is actionable: stay active, exercise, and watch your weight! But before going to a gym, have a close look at the number of COVID-19 cases in your area. Deep breathing (and grunting!) are excellent ways of producing virus-containing aerosols, which could infect you when you breath the aerosols, or touch equipment where droplets landed on. But there are plenty of at-home and outdoors exercise activities - from biking to windsurfing.