In Part #2 of this post I discussed community risk as if all members of the community had the same risk of severe illness and death if infected with SARS-CoV-2, which we all know isn’t true. While a small number of people may have a genetic quirk that makes them uniquely susceptible to this infection at any age, severe disease and fatality rates are most closely tied to age and health. This infection does not move through our population equally. While many of us turn down our anxiety dials a little bit, taking some comfort in the high numbers of people who are asymptomatic or have COVID symptoms but recover well (Perspective, Part 2), others of us have good reason to worry because we fall into a known high risk category due to more advanced age or underlying health conditions. This brings me back to the point I hope I made in Part 2, that all of us must consider overall risk to our communities, even if our own personal risk level isn’t especially high. We must be careful and vigilant to protect those that are more at risk from this infection and to protect how our community functions overall. High infection rates mean more sick people, which means more hospitalizations, more fatalities, fewer workers, and more restrictions. And none of us want any of that!
How does age impact disease severity?
I live in Massachusetts, which posts a daily coronavirus ‘dashboard’ that summarizes a variety of numbers related to the coronavirus pandemic in Massachusetts. A number of states are providing similar dashboards. You can find the MA Covid Response page here, which provides links to a variety of report, including the daily Dashboard. In Massachusetts, the average age of people diagnosed with COVID-19 is 51, and the average age of those who died is 82.
I took Barchart #2 from the MA Dashboard. It shows the number of people, per 100,000, who were hospitalized due to severe COVID symptoms for each age group. While adults between the ages of 20-79 have roughly the same rate of infection (barchart 1 in Part 2), people under 50 have a low likelihood of experiencing severe symptoms, especially compared with those who are 70 and older. Those over 80 are both more likely to test positive for infection and experience severe symptoms than all other age groups.
A better way of showing these data is compare, for each age group, the percent of coronavirus-positive people that were hospitalized due to severe symptoms (barchart #3, blue bars). We can see that the percent of people who have tested positive and were hospitalized due to symptom severity rises with age, but is generally low (<%5) for people under 50. For those in their 50s the chances are about 8%; the numbers rise to 15% or more for those over the age of 60. The red bars show the percent of people who were coronavirus positive who died (MA Dashboard). We can see that the fatality rate in people under the age of 50 is quite low (<0.5%). Though the risk of being hospitalized is higher in those 50 to 70, the fatality rate is between 2-6% of those known to have a SARS-CoV-2 infection. The situation is much worse for those 70 and up, with fatality rates of 19% and 35%, respectively.
A very important disclaimer for both hospitalization and fatality data: the numbers I show in this post depend both on infection rates and testing rates. If a person is infected but never experiences COVID symptoms and has no other reason to be tested, they will not show up in the data presented here. Remember, around 40% of people (80% for those under 20) who are infected with this virus may be asymptomatic, and if asymptomatic, may never be tested for SARS-CoV-2. An unknown number of people in each age class were infected but not tested or hospitalized and did not die from the infection, make the ‘real’ hospitalization and fatality rates potentially up to 40% lower than what I’m showing here, except for the 80+ age class, which both has a higher testing rate and a lower rate of asymptomatic infections (though as many as 30% of those 70 or older may be asymptomatic)
Why does age impact disease severity?
In the previous post (Part 2) I described the immune system as being a toolbox full of tools we are born with (innate immunity, HLA molecules) and ones that we make over time based on previous infections and vaccinations (adaptive immunity like B and T cells). How well we respond to a new challenge depends on whether we already have tools that can handle that challenge (immune memory cells), or if we have to make new ones (going all the way through a ‘primary’ immune response). Both depend on how well our immune system is functioning overall: is our toolbox in good shape, or is it disorganized and full of holes? If our immune system is functioning well, tools to fight the infection will be available or made as needed, and will work well together. If our immune system is not functioning very well in response to this infection, due to genetic quirks, to poor overall health, or to general issues related to aging, key tools may not be available, and those we have may not work together ‘optimally’. In these cases, the immune system still recognizes and tackles the challenge of a SARS-CoV-2 infection, but aims poorly and misfires. The virus reproduces more and for longer than it would under a cleaner immune response, and the continued activity of the immune response begins to damage tissues and organs in our bodies.
Aging is a process that is built into our genetic makeup. We age, and die, to allow younger generations access to the resources we once used. Some species don’t have a strong aging process like ours (which is called senescence) and rely instead on predation, infection, resource limitation, and mishap to remove older individuals from the population. Senescence affects all of our cells and tissues; cells divide less often, cells and tissues begin to function less well. Evidence for this ‘slowing’ can be seen in our immune systems when we are in our 40’s, though we typically maintain robust immune function into our 60s. By 70 our immune system is no longer functioning as well or as efficiently as it did just 10 years earlier, though it is still functions pretty well.
Aging in the immune system affects our ‘made to order’ tools (our adaptive immunity) way more than the ones we were born with (our innate immunity). As immune memory cells die, we lose our ability to respond to the pathogens that triggered their formation, and we become susceptible to diseases we easily fought off in the past. At the same time, our ability to activate new T and B cells decreases, making it harder for us to develop antibodies and killer T-cells to respond to new infections. For more detailed information, try this source, and for a more general overview, try this entry in the Merck Manual or this article in Livescience.com. The end result is that older immune systems respond to infections less well because they are missing tools, have poorly functioning tools, and because the tools they have no longer work smoothly together.
Even so, our immune systems generally manage to fight off infections pretty well, so why is SARS-CoV-2 so especially bad for older people? Well, first and foremost, none of us have ever been exposed to this particular virus before. While it is possible that some of us may have some immune ‘cross-coverage’ because we’ve been exposed to other similar viruses, most of us go through a brand new immune response to this virus, a major undertaking for the immune system. Older people whose immune systems are not functioning at ‘peak level’ will have slower and less effective responses to this new pathogen. Because the adaptive immune response (our ‘made to order’ immune tools) isn’t as capable of clearing the viral infection, the innate immune response (our ‘ready-made’ tools, those we are all born with) plays an outsized role in trying to control the infection.
Innate immunity recognizes and attacks problems on a very broad scale. While innate immune cells can recognize “VIRUS”, they can’t identify the specific virus causing an infection. Innate immunity is essentially an ‘OMG there is a virus in here!’ response, but it can’t make tools (antibodies) that find and remove SARS-CoV-2 virus from the body. It can cause individual cells to basically ‘freak out’ about viral infection in general (by releasing cytokines called interferons), but it can’t make killer T-cells that find and destroy viral-infected cells. (If you are having a hard time picturing innate vs adaptive immunity, try this online learning website hosted by Harvard.)
The end result of this unbalanced, innate-heavy immune response is an excessive amount of inflammation and tissue damage in relation to the amount of virus that is cleared from infected tissues. Inflammation and tissue damage are especially bad in the lungs, where they lead to a decreased ability to get oxygen from the air. Inflammation and tissue damage are also very bad in the circulatory system, where they can lead to clotting, blockages and vessel damage. And inflammation, tissue damage, reduced oxygen, clotting, and circulatory damage are all very bad for other organs such as the kidneys, the liver, and the heart (for more info, follow this link to a WebMD page).
This is all very scary, I know. But remember that many things need to go wrong for the body to have this bad of a response to an infection. Even immune systems of elderly people have many checks and balances in place to prevent damage as a result of immune activation. Also remember that, as I said in Part 2 of this post, more elderly people are asymptomatic or experience symptoms and recover from this infection than die of it. Doctors and researchers are working hard to find ways to calm immune responses that have gotten out of control through the use of steroids and more targeted drugs (I plan to write more about this in a future post).
How does health impact disease severity?
In Massachusetts, 98% of the people who died from COVID-19 (MA Dashboard again) were listed as also having underlying conditions. At least 54% of those who died had previous hospitalizations. The CDC currently lists the following health issues for having an increased risk, at any age, of severe COVID-19 symptoms: serious heart conditions, COPD, sickle cell, chronic kidney disease, type 2 diabetes, cancer, taking transplant-rejection medicine, and having a BMI over 30 (a BMI over 40 doubles the risk). Other health issues that impact the lungs, heart, or circulatory system may also increase risk, though the numbers are less certain, including asthma, smoking, cystic fibrosis, high blood pressure, thalassemia, Type 1 diabetes, liver disease and pregnancy (also see this visual on the effect of different health issues on COVID-19 severity). Combining these health issues with an aging immune response is really what underlies the high hospitalization and fatality rates in the upper age ranges. And while younger people overall have a low risk hospitalization and death from COVID-19, those that do die from the infection almost always have underlying conditions.
When this virus started moving through our populations, most assumed it was primarily a respiratory virus like the flu virus, and we expected that those with health issues affecting the lungs would be most at risk for hospitalization and death. However, while lung health does play a role, heart disease and diabetes keep coming out as major risk factors. Our understanding of this infection has changed, and we now understand that while infection begins in the lungs, it also can have major impacts on the cardiovascular system. Where flu virus gains entry into cells using a molecule found on cells lining the respiratory system, the ‘way in’ for SARS-CoV-2, the ACE2 receptor, is found on the surfaces of many different cell types throughout the body, including the lungs, inside blood vessels and heart, and kidneys. The virus can infect these internal organs if the initial respiratory in infection allows virus to get into the bloodstream.
A key feature of any immune response is inflammation. In inflammation, local immune cells release signal molecules which cause blood vessels to leak fluid and immune cells into infected spaces, which results in swelling of the infected tissues. These signals also trigger defensive actions in surrounding cells to help reduce or block viral reproduction, and they activate nearby immune cells to find, kill and clear pathogens and infected cells. Inflammation is a crucial piece of the immune response, yet inflammation can result in disfunction and tissue damage. Normally regions of inflammation are local and limited, but if extensive inflammation happens in the lungs, in blood vessels, in the heart, it can lead to serious and possibly fatal damage.
Antibodies, the proteins released by B-cells which can find and bind virus, also trigger inflammation. When many antibodies bind viral targets, they build up in big netlike meshes called ‘aggregates’ that need to be cleared out by immune cells (macrophages). If antibodies aggregates build up on the insides of blood vessels, they can slow and trap red blood cells, leading to the formation of tiny blood clots and, more rarely, vascular inflammation, vessel constriction and blockage (MIS-C, sometimes referred to as Kawasaki disease, which may not be the same thing). Blood clots and constrictions can reduce bloodflow to key tissues in the kidneys, heart, and even brain, and play a major role in most COVID fatalities. Any underlying health conditions that affect cardiovascular health (heart disease, hypertension, sickle cell, obesity and diabetes) can impact the course of this infection. Combining cardiovascular health issues with a compromised immune system (age, disease) which may have a prolonged or misdirected immune response (and inflammation) is especially bad, which is why we see disease severity and fatality rates rise quite quickly after about age 60 for those with underlying health conditions.
Having respiratory health issues such as asthma makes the initial infection with SARS-CoV-2 dangerous, because both the infection and the lung health issue can reduce how well the lungs work to deliver oxygen to the blood. However, if the infection stays in the lungs, a person is generally health otherwise, has a healthy immune system AND access to oxygen if they need it, people with respiratory issues can survive a SARS-CoV-2 infection as well those in their age range who do not have underlying respiratory conditions, though the same is not true for those who have COPD, who are at high risk of having severe COVID-19 symptoms.
In a way, we were lucky with this pandemic…
Wait, what? How can I say that? Don’t get me wrong, this is a very serious problem we are facing. The virus is definitely dangerous and obviously can be deadly. No one on the planet had immunity to this particular virus when it got started – that is a major ‘yikes!’ factor right there.
But here’s how we are lucky with this particular pandemic. The transmission rate, with one infected person infecting maybe three new people, is nowhere near that of the measles virus, where one infected person can infect eighteen new people. Unlike Ebola, the COVID virus can’t infect people through the skin: touching it won’t infect you unless you then bring the virus to your eyes, nose or mouth. Children rarely get seriously sick or die from this infection. A sizable number of people of all ages seem to have some protection already in place, possibly due to some ‘cross-over’ immunity from being exposed to other similar viruses in the past. If people do become infected, most get better after about two weeks, but some don’t. This is a very serious virus for a for a fraction of our population. Not a small fraction, but also not a large fraction.
Here’s the thing. This will not be the only pandemic we face in the coming decades. Viruses can jump from other species to humans (and vice versa). When a virus jumps to a new species, no member of the that species has an immune memory to fight that virus. The chance of an infected animal passing a virus to a human is very, very low, and the chance of that human then passing it to another human is also very low. Before global travel, even if a ‘new’ virus (new to us, anyway) could move from animal to person, and then person to person, they tended to be isolated geographically, dying out over time before they could become a global pandemic.
BUT think about how many times a day on this planet a human interacts with an animal, either knowingly (in agriculture, as a pet, or preparing meat), or unknowingly (feces, bites, via vectors like fleas or mosquitoes). And then think about how many times in a day one human interacts with another. Even if the chances of a virus jumping into a human population are extremely low (which they are), if you tempt fate repeatedly over time (which we do), it will happen, and if that new disease can jump from human to human, it will do so, for as long as it encounters humans who are not immune to it. Now think about how much travel people do every day, between towns, states, countries…
We will have another pandemic at some point, and likely fairly soon. We weren’t really even taken by surprise with this one. If you Google “pandemic preparedness plan” and “.pdf”, you will discover plans written by the WHO, the CDC, the DOE, individual states, and even universities and businesses well before 2020. In 2009 the World Health Organization published a “Top 5” list of likely that included coronaviruses. While we didn’t know about this particular virus, we definitely knew that coronaviruses as a group had great potential for causing epidemic illness. So, how do you think we are doing in our response to something we knew might be a problem AND turned out to be not nearly as bad as it could have been? How well will we respond to the next one?
Science in Translation 