There is a lot of attention being paid to the proportions of severe and fatal cases in discussions of COVID-19. Unless you’ve been living under a rock since January, you know that there are groups who are more likely to get very sick or die during this pandemic. In this post, we explore the evidence and working theories behind why these groups might be at higher risk.
The CDC outlined three broad groups at high risk of contracting a severe illness. These are:
- People age 65 years and up
- People living in nursing homes or long term care facilities
- People of any age with underlying medical conditions.
In addition to these, several other factors may predispose people to more severe COVID-19 illness. Male sex and African American race are two critical demographics in particular, which researchers are actively exploring. Also, the influence of behavioral risk factors such as history as a smoker and substance use are not fully understood. For now, we’ll stick with the recognized factors, and I promise to circle back and update the evidence as this builds.
We’ve all heard the public service announcements, but what does it mean to be high risk? Why are older folks at greater risk? What do chronic illnesses like hypertension and heart disease have to do with COVID-19?
Age
Before we begin, it is essential to recognize that almost all information comes from fast-moving, incomplete data. The lack of robust testing in the US means that our own data is likely under-counting the number of cases, and that could vary between age groups and other demographics.
We have no idea what the community prevalence of COVID-19 is, overall or in any subgroup (the “denominator”). There is almost certainly bias in who gets tested and how a positive test is being treated (i.e., sent home or admitted to the hospital) based on age. Susceptibility in older ages may have driven those in older age groups to be more proactive in seeking healthcare visits and testing, actually driving down the proportion of admissions and adverse outcomes by expanding the denominator.
The CDC reported analysis from 2,449 of the first 4,226 US cases (Feb 12-Mar 16; with sufficient outcome data available) and estimated the case-fatality proportion for those aged 85 or older to be between 10.4-27.3% (data quality was apparently terrible). Compare this to a case fatality proportion of 0% (none) in those under 20 years old. Admissions to the hospital ranged from 31.3-70.3% compared to 1.6-2.5% in those under 20. Estimates from a more recent publication in Lancet from the Imperial College of London estimated that 13.4% of patients over 80 died from it, while just 1.25% in their 50s and 0.3% in their 40s died from the infection. This does not mean that younger folks are off the hook! While death is less likely, the distribution of cases and hospitalizations in the US is more evenly distributed across age groups than first expected.
Why is older age a risk factor?
Indeed, part of the story is that older people have a greater burden of disease compared to younger folks. That answer doesn’t seem to tell the whole story. The rest may lie in how we define “frailty” in studies of aging. Clinicians consider frail, older patients to be less resilient and have less ability to rebound after injuries and illnesses. They tend to have higher symptom burdens for their illnesses, advanced complexity of medical conditions, and a lower tolerance for treatments. It is not a binary condition and increases over time. And while frailty progresses with age, it doesn’t develop uniformly. Some people grow frail faster than others, so a person in good health over 80 may recover better than someone considered more ‘frail’ in a younger age group.
Frailty ties directly to the degradation of the immune system as people age. This may include slowing the T cell response and decreasing the accuracy with which the T cells translate what the leukocytes show them. T cells translate viral antigens from leukocytes into antibodies (produced by B cells). Once they do this, they retain the memory of that particular threat, leaving fewer “naïve” T cells behind. At puberty, the number of T cells is a tenth that of early childhood. This drops another 90% from there by age 40 or 50 and continues to decline.
Unfortunately, this reduced immunologic memory means that even if older folks get the disease and survive, they are less likely to be prepared if another wave of the disease returns – which many experts believe will happen.
Nursing homes and long-term care facilities
Naturally, part of the risk to people living in nursing homes stems from the age of the residents. These are elderly individuals who are likely to be more frail than their peers still living in the community. Nursing homes also increase the complexity and frequency of close interactions between residents and caregivers, increasing the risk of transmission without aggressive infection control measures in place. The first outbreak in a nursing home facility came in late February in Kirkland, Washington.
Former director of the CDC Tom Frieden referred to this facility as ‘ground zero’ in the US pandemic. Washington State was hit hard by the outbreak, so it’s no surprise that their nursing homes are hard hit as well. A recent report in the New England Journal of Medicine characterized one Seattle facility’s outbreak, which led to 167 confirmed cases alone (101 residents, 50 healthcare staff, and 16 visitors). They also noted that as of March 18th, there were 30 facilities with at least one confirmed case in King County, where Seattle is located.
In response, the Centers for Medicare and Medicaid Services has advised nursing homes to restrict ALL visitors and non-essential personnel since March 13th [pdf]. The CDC has released special, supplementary guidance for nursing homes and long-term care facilities above and beyond their broader Interim Guidance on infection prevention and control for COVID-19. Yet, the number of long-term care facilities reporting infections continues to multiply, topping 400 in late March.
Underlying medical conditions
There is strong evidence now that several types of chronic illnesses are associated with greater disease severity. There is also some conflicting evidence that certain illnesses may increase the risk of transmission. Given that countries all over the world have struggled to accurately measure the community spread of the disease (we don’t have a denominator), this remains an open question.
Early on, the overall number of chronic illnesses was associated with severe outcomes in a retrospective cohort of 1590 cases from China – with severe outcomes in 19.3% of those with pre-existing illness and 28.5% of those with 2 or more illnesses, compared to 8.3% overall. From there, the impacts of specific illnesses were quickly uncovered. Per the CDC, this list now consists of:
- “People with chronic lung disease or moderate to severe asthma
- People who have serious heart conditions
- People who are immunocompromised
- Many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV or AIDS, and prolonged use of corticosteroids and other immune weakening medications
- People with severe obesity (body mass index [BMI] of 40 or higher)
- People with diabetes
- People with chronic kidney disease undergoing dialysis
- People with liver disease.”
Why are these chronic illnesses increasing risk?
Is there a relationship between age and chronic conditions? The researchers and journalists at the COVID Tracking Project put this very succinctly:
“Older people are much more likely than young people to have lung disease, kidney disease, hypertension, or heart disease, and those conditions are more likely to transform a coronavirus infection into something nastier.”
Researchers have tied many of these chronic illnesses to weakened overall immune function for decades. This is very likely to play a role in the susceptibility of onset of severe illness in the folks who catch SARS-CoV-2. In broad terms, many chronic illnesses influence the entire body by starting chain reactions to natural inflammatory responses. This effect of chronic diseases of the heart and lungs are particularly well known.
According to a recent publication in the CDC’s Morbidity and Mortality Weekly Report (MMWR) describing the first hospitalization records gathered by their COVID-19 Surveillance Network (COVID-NET), rates of comorbidities were dramatically higher than the general population. This included hypertension (49.7% vs 45% of the general US population), obesity (48.3% vs 39.8%), chronic lung disease (34.6% vs 13.6%), diabetes mellitus (28.3% vs 10.5%), and non-hypertensive cardiovascular disease (27.8% vs 9%).
Diabetes as an example
Diabetes (approximately 10.5% of the US population) is a perfect example of a risk factor that has strong, long-recognized ties to inflammation and weakened immune systems. In the case of Type 2 Diabetes, the inflammation seems to be a direct reaction to high blood sugar levels by the immune system itself.
Type 1 diabetes is itself an autoimmune disorder, although the focus of the attack seems to be on beta cells in the pancreas and not the overall body. However, the whole immune system compromise that leads to the condition means that the immune system is over-worked and making mistakes. Without good control of blood sugar, the disease’s attacks are known to weaken the overall immune system’s ability to respond to threats outside the body.
The medical and public health community is constantly learning more about this virus and the disease it causes. We will continue to gather insights and information into the drivers of the COVID-19 illness that results from infection. In the meantime, be safe, stay home, and – just in case anyone hasn’t suggested it recently – wash your hands!
Ben King