Why COVID-19 kills some people and spares others. Here's what scientists are finding.

The SARS-CoV-2 virus invades human cells by attaching to ACE2 receptors on the surfaces of those cells.
The SARS-CoV-2 virus invades human cells by attaching to ACE2 receptors on the surfaces of those cells. (Image credit: Shutterstock)

The novel coronavirus causing COVID-19 seems to hit some people harder than others, with some people experiencing only mild symptoms and others being hospitalized and requiring ventilation. Though scientists at first thought age was the dominant factor, with young people avoiding the worst outcomes, new research has revealed a suite of features impacting disease severity. These influences could explain why some perfectly healthy 20-year-old with the disease is in dire straits, while an older 70-year-old dodges the need for critical interventions.

Underlying health conditions are thought to be an important factor influencing disease severity. Indeed, a study of more than 1.3 million COVID-19 cases in the United States, published June 15 in the journal Morbidity and Mortality Weekly Report, found that rates of hospitalizations were six times higher and rates of death were 12 times higher among COVID-19 patients with underlying conditions, compared with patients without underlying conditions. The most commonly reported underlying conditions were heart disease, diabetes and chronic lung disease. 

In general, risk factors for more severe COVID-19 outcomes include:
Age
Diabetes (type 1 and type 2)
Heart disease and hypertension
Smoking
Blood type
Obesity
Genetic factors

Age

About 8 out of 10 deaths associated with COVID-19 in the U.S. have occurred in adults ages 65 and older, according to the U.S. Centers for Disease Control and Prevention (CDC). The risk of dying from the infection, and the likelihood of requiring hospitalization or intensive medical care, increases significantly with age. For instance, adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%. 

The trend may be due, in part, to the fact that many elderly people have chronic medical conditions, such as heart disease and diabetes, that can exacerbate the symptoms of COVID-19, according to the CDC. The ability of the immune system to fight off pathogens also declines with age, leaving elderly people vulnerable to severe viral infections, Stat News reported.

Related: Coronavirus in the US: Latest COVID-19 news and case counts

Diabetes

Risk factors for severe COVID-19 infection.

(Image credit: Shutterstock)

Diabetes mellitus — a group of diseases that result in harmful high blood sugar levels — also seems to be linked to risk of more severe COVID-19 infections. 

The most common form in the U.S. is type 2 diabetes, which occurs when the body's cells don't respond to the hormone insulin. As a result, the sugar that would otherwise move from the bloodstream into cells to be used as energy just builds up in the bloodstream. (When the pancreas makes little to no insulin in the first place, the condition is called type 1 diabetes.)

In a review of 13 relevant studies, scientists found that people with diabetes were nearly 3.7 times more likely to have a critical case of COVID-19 or to die from the disease compared with COVID-19 patients without any underlying health conditions (including diabetes, hypertension, heart disease or respiratory disease), they reported online April 23 in the Journal of Infection.

Even so, scientists don't know whether diabetes is directly increasing severity or whether other health conditions that seem to tag along with diabetes, including cardiovascular and kidney conditions, are to blame. 

That fits with what researchers have seen with other infections and diabetes. For instance, flu and pneumonia are more common and more serious in older individuals with type 2 diabetes, scientists reported online April 9 in the journal Diabetes Research and Clinical Practice. In a literature search of relevant studies looking at the link between COVID-19 and diabetes, the authors of that paper found a few possible mechanisms to explain why a person with diabetes might fare worse when infected with COVID-19. These mechanisms include: "Chronic inflammation, increased coagulation activity, immune response impairment and potential direct pancreatic damage by SARS-CoV-2."

Related: 13 coronavirus myths busted by science 

Mounting research has shown the progression of type 2 diabetes is tied to changes in the body's immune system. This link could also play a role in poorer outcomes in a person with diabetes exposed to SARS-CoV-2, the virus that causes COVID-19. 

No research has looked at this particular virus and immune response in patients with diabetes; however, in a study published in 2018 in the Journal of Diabetes Research, scientists found through a review of past research that patients with obesity or diabetes showed immune systems that were out of whack, with an impairment of white blood cells called Natural Killer (NK) cells and B cells, both of which help the body fight off infections. The research also showed that these patients had an increase in the production of inflammatory molecules called cytokines. When the immune system secretes too many cytokines,a so-called "cytokine storm" can erupt and damage the body's organs. Some research has suggested that cytokine storms may be responsible for causing serious complications in people with COVID-19, Live Science previously reported. Overall, type 2 diabetes has been linked with impairment of the very system in the body that helps to fight off infections like COVID-19 and could explain why a person with diabetes is at high risk for a severe infection.

Not all people with type 2 diabetes are at the same risk, though: A study published May 1 in the journal Cell Metabolism found that people with diabetes who keep their blood sugar levels in a tighter range were much less likely to have a severe disease course than those with more fluctuations in their blood sugar levels. 

People with type 1 diabetes (T1D) are also at elevated risk of adverse outcomes, a small study published in Diabetes Care suggests. The study, coordinated by  T1D Exchange — a nonprofit research organization focused on therapies for those with type 1 diabetes — found that of 64 people with either COVID-19 or COVID-19-like symptoms, two died. Nearly 4 in 10 people had to be treated in a hospital. And nearly a third experienced diabetic ketoacidosis — a potentially deadly condition in which the body experiences a shortage of insulin and blood sugar levels rise dangerously high.  The average patient was about 21 years old, suggesting that risks could be potentially higher for older age groups.

Heart disease and hypertension

Risk factors for severe COVID-19 infection.

(Image credit: Shutterstock)

People with conditions that affect the cardiovascular system, such as heart disease and hypertension, generally suffer worse complications from COVID-19 than those with no preexisting conditions, according to the American Heart Association. That said, historically healthy people can also suffer heart damage from the viral infection. 

The first reported coronavirus death in the U.S., for instance, occurred when the virus somehow damaged a woman's heart muscle, eventually causing it to burst, Live Science reported. The 57-year-old maintained good health and exercised regularly before becoming infected, and she reportedly had a healthy heart of "normal size and weight." A study of COVID-19 patients in Wuhan, China, found that more than 1 in 5 patients developed heart damage — some of the sampled patients had existing heart conditions, and some did not. 

In seeing these patterns emerge, scientists developed several theories as to why COVID-19 might hurt both damaged hearts and healthy ones, according to a Live Science report

In one scenario, by attacking the lungs directly, the virus might deplete the body's supply of oxygen to the point that the heart must work harder to pump oxygenated blood through the body. The virus might also attack the heart directly, as cardiac tissue contains angiotensin-converting enzyme 2 (ACE2) — a molecule that the virus plugs into to infect cells. In some individuals, COVID-19 can also kickstart an overblown immune response known as a cytokine storm, wherein the body becomes severely inflamed and the heart could suffer damage as a result.

Smoking

Risk factors for severe COVID-19 infection.

(Image credit: Shutterstock)

People who smoke cigarettes may be prone to severe COVID-19 infections, meaning they face a heightened risk of developing pneumonia, suffering organ damage and requiring breathing support. A study of more than 1,000 patients in China, published in the New England Journal of Medicine, illustrates this trend: 12.3% of current smokers included in the study were admitted to an ICU, were placed on a ventilator or died, as compared with 4.7% of nonsmokers. 

Cigarette smoke might render the body vulnerable to the coronavirus in several ways, according to a recent Live Science report. At baseline, smokers may be vulnerable to catching viral infections because smoke exposure dampens the immune system over time, damages tissues of the respiratory tract and triggers chronic inflammation. Smoking is also associated with a multitude of medical conditions, such as emphysema and atherosclerosis, which could exacerbate the symptoms of COVID-19.

A recent study, posted March 31 to the preprint database bioRxiv, proposed a more speculative explanation as to why COVID-19 hits smokers harder. The preliminary research has not yet been peer-reviewed, but early interpretations of the data suggest that smoke exposure increases the number of ACE2 receptors in the lungs — the receptor that SARS-CoV-2 plugs into to infect cells. 

Many of the receptors appear on so-called goblet and club cells, which secrete a mucus-like fluid to protect respiratory tissues from pathogens, debris and toxins. It's well-established that these cells grow in number the longer a person smokes, but scientists don't know whether the subsequent boost in ACE2 receptors directly translates to worse COVID-19 symptoms. What's more, it's unknown whether high ACE2 levels are relatively unique to smokers, or common among people with chronic lung conditions.

Obesity

Several early studies have suggested a link between obesity and more severe COVID-19 disease in people. One study, which analyzed a group of COVID-19 patients who were younger than the age of 60 in New York City, found that those who were obese were twice as likely as non-obese individuals to be hospitalized and were 1.8 times as likely to be admitted into critical care. 

"This has important and practical implications" in a country like the U.S. where nearly 40% of adults are obese, the authors wrote in the study, which was accepted into the journal Clinical Infectious Diseases but not yet peer-reviewed or published. Similarly, another preliminary study that hasn't yet been peer-reviewed found that the two biggest risk factors for being hospitalized from the coronavirus are age and obesity. This study, published in medRxiv looked at data from thousands of COVID-19 patients in New York City, but studies from other cities around the world found similar results, as reported by The New York Times.

A preliminary study from Shenzhen, China, which also hasn't been peer-reviewed, found that obese COVID-19 patients were more than twice as likely to develop severe pneumonia as compared with patients who were normal weight, according to the report published as a preprint online in the journal The Lancet Infectious Diseases. Those who were overweight, but not obese, had an 86% higher risk of developing severe pneumonia than did people of "normal" weight, the authors reported. Another study, accepted into the journal Obesity and peer-reviewed, found that nearly half of 124 COVID-19 patients admitted to an intensive care unit in Lille, France, were obese.

It's not clear why obesity is linked to more hospitalizations and more severe COVID-19 disease, but there are several possibilities, the authors wrote in the study. Obesity is generally thought of as a risk factor for severe infection. For example, those who are obese had longer and more severe disease during the swine flu epidemic, the authors wrote. Obese patients might also have reduced lung capacity or increased inflammation in the body. A greater number of inflammatory molecules circulating in the body might cause harmful immune responses and lead to severe disease.

Blood type

Risk factors for severe COVID-19 infection.

(Image credit: Shutterstock)

Blood type seems to be a predictor of how susceptible a person is to contracting SARS-CoV-2, though scientists haven't found a link between blood type per se and severity of disease.

Jiao Zhao, of The Southern University of Science and Technology, Shenzhen, and colleagues looked at blood types of 2,173 patients with COVID-19 in three hospitals in Wuhan, China, as well as blood types of more than 23,000 non-COVID-19 individuals in Wuhan and Shenzhen. They found that individuals with blood types in the A group (A-positive, A-negative and AB-positive, AB-negative) were at a higher risk of contracting the disease compared with non-A-group types. People with O blood types (O-negative and O-positive) had a lower risk of getting the infection compared with non-O blood types, the scientists wrote in the preprint database medRxiv on March 27; the study has yet to be reviewed by peers in the field.

In a more recent study of blood type and COVID-19, published online April 11 to medRxiv, scientists looked at 1,559 people tested for SARS-CoV-2 at New York Presbyterian hospital; of those, 682 tested positive. Individuals with A blood types (A-positive and A-negative) were 33% more likely to test positive than other blood types and both O-negative and O-positive blood types were less likely to test positive than other blood groups. (There's a 95% chance that the increase in risk ranges from 7% to 67% more likely.) Though only 68 individuals with an AB blood type were included, the results showed this group was also less likely than others to test positive for COVID-19. 

The researchers considered associations between blood type and risk factors for COVID-19, including age, sex, whether a person was overweight, other underlying health conditions such as diabetes mellitus, hypertension, pulmonary diseases and cardiovascular diseases. Some of these factors are linked to blood type, they found, with a link between diabetes and B and A-negative blood types, between overweight status and O-positive blood groups, for instance, among others. When they accounted for these links, the researchers still found an association between blood type and COVID-19 susceptibility. When the researchers pooled their data with the research by Zhao and colleagues out of China, they found similar results as well as a significant drop in positive COVID-19 cases among blood type B individuals.

Why blood type might increase or decrease a person's risk of getting SARS-CoV-2 is not known. A person's blood type indicates what kind of certain antigens cover the surfaces of their blood cells; These antigens produce certain antibodies to help fight off a pathogen. Past research has suggested that at least in the SARS coronavirus (SARS-CoV), anti-A antibodies helped to inhibit the virus; that could be the same mechanism with SARS-CoV-2, helping blood group O individuals to keep out the virus, according to Zhao's team.

Genetic factors

Risk factors for severe COVID-19 infection.

(Image credit: Shutterstock)

Many medical conditions can worsen the symptoms of COVID-19, but why do historically healthy people sometimes fall dangerously ill or die from the virus? Scientists suspect that certain genetic factors may leave some people especially susceptible to the disease, and many research groups aim to pinpoint exactly where those vulnerabilities lie in our genetic code. 

In one scenario, the genes that instruct cells to build ACE2 receptors may differ between people who contract severe infections and those who hardly develop any symptoms at all, Science magazine reported. Alternatively, differences may lie in genes that help rally the immune system against invasive pathogens, according to a recent Live Science report.

For instance, a study published April 17 in the Journal of Virology suggests that specific combinations of human leukocyte antigen (HLA) genes, which train immune cells to recognize germs, may be protective against SARS-CoV-2, while other combinations leave the body open to attack. HLAs represent just one cog in our immune system machinery, though, so their relative influence over COVID-19 infection remains unclear. Additionally, the Journal of Virology study only used computer models to simulate HLA activity against the coronavirus; clinical and genetic data from COVID-19 patients would be needed to flesh out the role of HLAs in real-life immune responses.

Originally published on Live Science.  

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  • ediso74
    admin said:
    The novel coronavirus causing COVID-19 seems to hit some people harder than others, with some people experiencing just mild symptoms and others being hospitalized and requiring ventilation. Here's why.

    Why COVID-19 kills some people and spares others. Here's what scientists are finding. : Read more
    Ok, I will bite. How does 80% (8 out of 10) = 11% + 27% (38%) ?

    "About 8 out of 10 deaths associated with COVID-19 in the U.S. have occurred in adults ages 65 and older, according to the U.S. Centers for Disease Control and Prevention (CDC). The risk of dying from the infection, and the likelihood of requiring hospitalization or intensive medical care, increases significantly with age. For instance, adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%. "
    Reply
  • ediso74
    ediso74 said:
    Ok, I will bite. How does 80% (8 out of 10) = 11% + 27% (38%) ?

    "About 8 out of 10 deaths associated with COVID-19 in the U.S. have occurred in adults ages 65 and older, according to the U.S. Centers for Disease Control and Prevention (CDC). The risk of dying from the infection, and the likelihood of requiring hospitalization or intensive medical care, increases significantly with age. For instance, adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%. "
    I see that the writer pulled the stats directly from CDC website but misunderstood them. I believe the last two percentages is the percentage of confirmed cases for the age group that ended in death due to the virus, not the percentage of overall deaths. Livescience needs to vet their articles better else they become yet another source of misinformation.
    Reply
  • edwardinchina
    To reiterate and add a link.

    They have misquoted CDC. See this: See below for estimated percent of adults with confirmed COVID-19 reported in the U.S:
    https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/older-adults.html
    If most of the confirmed cases are 65+ then the math can work out.
    Reply
  • zinn
    From the article: "These influences could explain why some perfectly healthy 20-year-old with the disease is in dire straits, while an older 70-year-old dodges the need for critical interventions. " Nothing in this article explained why some 20's get real sick and 70's don't except for a vague reference that blood type or genetics might be a factor.. This article contained nothing new.. Stuff I've already read a thousand times..
    Reply
  • grecchia
    In addition to the flat-out wrong percentages already mentioned, "Though scientists at first thought age was the dominant factor..." is radically misleading. It has been extremely well borne out that age is the dominant factor associated with risk, as the CDC stats make clear: https://data.cdc.gov/NCHS/Provisional-COVID-19-Death-Counts-by-Sex-Age-and-S/9bhg-hcku/data . As noted in https://www.medrxiv.org/content/10.1101/2020.05.21.20108969v1 , completely uncontrolled diabetes gives one the vulnerability of someone approximately 10 years older than they are, as does a BMI above 40; using the figures in the article about blood type, having type A is equivalent to 3 years' risk (95% confidence interval 1 year to 6 years). A far cry from age not being the dominant factor!
    Reply
  • Michael0915
    here in NY the areas which have fared worst have higher levels of air pollution resulting in asthma and a diet high in processed food (higher obesity rate and victims of the diabetes epidemic), so this pandemic has brought greater awareness to modifying to a more healthy diet as well as switching to renewables for better air quality. Cuomo showed during one of his pressers that a survey taken by local hospitalizations showed that pre-existing conditions was the major underlying factor behind hospitalizations, 96% Being outside or even working in the healthcare field was much less of an indicator.
    Reply
  • AnthonySouls
    ediso74 said:
    Ok, I will bite. How does 80% (8 out of 10) = 11% + 27% (38%) ?

    "About 8 out of 10 deaths associated with COVID-19 in the U.S. have occurred in adults ages 65 and older, according to the U.S. Centers for Disease Control and Prevention (CDC). The risk of dying from the infection, and the likelihood of requiring hospitalization or intensive medical care, increases significantly with age. For instance, adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%. "

    I think the article got the statistics from an article similar to this one:
    https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm#T1_down
    As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years.

    The same article has
    This first preliminary description of outcomes among patients with COVID-19 in the United States indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years.

    Further on,
    Among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years (Table) (Figure 2).

    This explains there methodology:
    The lower bound of these percentages was estimated by using all cases within each age group as denominators. The corresponding upper bound of these percentages was estimated by using only cases with known information on each outcome as denominators.

    10% - 27% and 3% - 11% are based on reported age, while 34% and 46% (80%) seem to be based on known outcome. These were from 4,226 COVID-19 cases that state and CDC confirmed back in March; the data was missing'/incomplete.

    It seems they are using different sampling criteria for each.
    Reply
  • SeattleTabby
    admin said:
    The novel coronavirus causing COVID-19 seems to hit some people harder than others, with some people experiencing just mild symptoms and others being hospitalized and requiring ventilation. Here's why.

    Why COVID-19 kills some people and spares others. Here's what scientists are finding. : Read more

    The numbers on "people over 65" are misleading and dangerous. Many people in that age group have comorbidities and many live in nursing homes or other environments where they can't escape close contact from others. When you separate out nursing home occupancy and comorbidities, the age differences vanish. Immunosenescence varies widely among people over 65 and appears very low among people who are physically fit. I discuss this at length with references in my article http://mycopy.info/agemed
    Mexico never saw older people at extreme risk. In that country, comorbidities occur at all ages and few nursing homes exist.

    This is ageism, pure and simple.One geriatrician (quoted in my article) says a fit person who's 80 has a better chance of surviving than a 60yo with underlying conditions. .
    Reply
  • AdamSmith37
    Even at this late date, we still know so very little about Covid-19. Lots of stats and numbers, but do we ever correlate these with what might have happened to these same people in the absence of their having been tagged with Covid-19? For instance, if "adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%", how many of these deaths would have been normal to experience, in the absence of Covid-19? We see so much distortion of the limited info that is available to us, that many people think the numbers are stacked against normalcy and in favor of the culprit Covid-19. Until we start to compare apples with apples, this perception of distortion will continue. We read about numerous instances of people dying from obvious other reasons but still being listed as having died from Covid-19, including car or motorcycle accidents, heart attacks, cancers, etc. During the New York onslaught, the news media stated that the Governor had instructed medical people to simply list all deaths as Covid-19 caused, perhaps to underscore their apparent need for Federal aid. Many other strange things are occurring throughout the world. How are people to get a grip on the true numbers, and more importantly, how are scientists and the medical community to really know what they are dealing with when there is so much distortion of numbers? When I took statistics class years ago I learned that people can make statistics say whatever they want, regardless of reality.

    I appreciate the opportunity to discuss things about Covid-19 without being accused of being conspiracy theorists etc. There is so much that still needs to be addressed if we are ever going to get to the true cause(s) and means to possibly deter or prevent this virus from again attacking us. For instance, is there a possible connection to atmospheric and/or man-made electricity, as is inferred towards influenza by Arthur Firstenberg in his 2017 publication of "The Invisible Rainbow"? Several hundred years ago, influenza spread faster than people and showed up on ships that had been at sea for three months. Then after it had run its course, it disappears as quickly as it had appeared. A week or two ago, it was mentioned in the news that they were studying people's stomachs and determined that we all have over a thousand viruses within us. Perhaps we all already have these, including Covid-19, within us but that they only get out of whack and seriously surface when they are triggered by extreme exposure to various unseen electricity or some other odd combination of things.

    Sun spots and their cycle apparently peaked around late 2019 but this can then go on for several years before dwindling and resting for a few years. Flu virus epidemics surfaced on many occasions when this similar situation occurred and in 1918-1920 we were also developing radio waves with enormous amounts of non-ionizing radiation spread around the world. Again in WWII we were developing radar and today we are developing 5-G which is going to be blasted from tens of thousands of satellites and around 1,000,000 land stations in the US alone. These 5-G devices operate with unprecedented non-ionizing electrical microwaves at 30-300 giga (billion) hertz while a normal cell phone is around 9 hertz. This is scary to me and I wonder if we will maybe end up sterilizing people, animals and plants from the entire planet? Our technology revolution is happening so fast that we barely have time to invent one thing and then another comes along that makes the previous invention obsolete. There is barely time to build/implement things much less test them for safety, and those who are supposed to be watch-dogs are busy counting their new-found money before they deposit - they could care less if their actions destroy the world as long as they get theirs. We all need to look around us and see the forest for the trees in addition to just the trees.
    Reply
  • Nonsmiley
    Nothing here about the association between vitamin D deficiency and Covid-19.
    Reply