Covid-19 risk factors: How chronic stress and coronavirus might be linked

2020 has been remarkably stressful — from the fear of nuclear war to a presidential impeachment to a pandemic that has killed more than 186,000 Americans as of September 3. And let’s not forget the record unemployment, the school closures, the police killing of George Floyd and other people of color, the months of protests against police brutality and systemic racism, and accelerating climate change.

Many Americans are understandably feeling anxious about this cascade of events — on top of any stressors they may have already been dealing with. “The technical term is, ‘It’s a lot,’” says Linda Goler Blount, president and CEO of the Black Women’s Health Imperative.

A Centers for Disease Control and Prevention survey of 5,412 people in late June found that 31 percent were experiencing symptoms of anxiety and depression, about three times the number of respondents who said the same in the first two quarters of 2019. Another 26 percent reported symptoms of a trauma- or stressor-related disorder. Eleven percent of people said they had seriously considered suicide in the previous 30 days.

Now some researchers are asking if stress — especially chronic stress — might be another preexisting condition that makes Covid-19 infections worse.

Our bodies have evolved to respond in the moment to stressful situations, both physical and emotional. This is often called the “fight-or-flight” response, and it helps us react quickly to danger. But when this becomes a long-term response, these involuntary reactions can be harmful.

There isn’t a single agreed-upon definition of what “chronic” means, though some researchers think stress that persists for weeks or months likely qualifies. Generally, “People thinking about something consistently over time qualifies as a chronic stressor,” says Paula Braveman, director of the Center on Social Disparities in Health at the University of California San Francisco.

Other researchers say an important feature of chronic stress is its instability, of not knowing whether or when the stressor will end. (The pandemic seems to fit the bill.) Still others define it as the body’s inability to return to base level amounts of important hormones, often developing a new, elevated “normal” for stress hormones such as cortisol.

Cortisol is an important part of the stress response, and new research suggests cortisol levels appear to impact the severity of Covid-19. There’s still a lot we don’t understand about the relationship between the two, but clinical trials of a Covid-19 treatment using dexamethasone — a drug that reduces the body’s natural cortisol production, as well as inflammation — has been found to help critically ill patients.

“High levels of cortisol are associated with poor [Covid-19] outcomes, and drugs that block the hormone seem to improve outcomes,” says Kavita Vedhara, a University of Nottingham professor of health psychology who is conducting an ongoing study on Covid-19 and stress. Vedhara says that while further research is needed, she wouldn’t be surprised if chronic stress was found to be a risk factor for a severe case of Covid-19. “It fits with what we know about psychological stress generally, and in particular the evidence on stress and other viral infections,” she added.

Understanding how stress impacts Covid-19 could hold clues for preventing or reducing the severity of infections, as well as responding to the inequities that put some racial and minorities groups at greater risk.

Can chronic stress make us more susceptible to infection — and more severe infection?

Fifty years of research on stress suggests it has a profound effect on the body, influencing everything from memory to the way the body stores fat. It’s even been found to cause structural changes in the brain.

In general, “Chronic stress wears the body down,” says Kathryn Freeman Anderson, a sociology professor at the University of Houston. Over time, stress keeps the body locked into a heightened response, resulting in damage somewhat similar to an engine idling for too long.

Prolonged stress also weakens the immune system. In 1991, scientists studying the relationship between psychological stress and immune response intentionally exposed 394 healthy participants to one of five respiratory viruses, including a coronavirus. The subjects were then quarantined and monitored. Even after controlling for factors like age, sex, education, weight, and prior antibody status, the researchers found that a person’s underlying stress levels were associated with an increased risk of getting sick. Since then, dozens of studies have shown that chronic stress increases the risk of not only catching the common cold but also developing conditions such as asthma and Alzheimer’s disease, among others.

Chronic stress can also make vaccines less effective. One study compared the vaccine responses of 32 caregivers of a spouse with dementia — a role associated with chronic stress — against 32 subjects in a control group. After vaccinating both groups against influenza, the researchers found that the caregivers’ stress was associated with a lowered antibody response, meaning less protection against the flu.

Conversely, in 2018, Vedhara designed an experiment for 138 older adults to see whether a positive mood could have a protective effect. For two weeks before and four weeks after their annual flu shot, participants self-reported how they felt using a diary. Vedhara found that psychological influences, including stress and mood, influenced participants’ antibody response. (Stress responses are often measured by observing specific emotional states.)

Vedhara found that if participants felt unstressed and upbeat, particularly on the day they were vaccinated, the vaccine worked better. The effect on antibody production was about as large as the effect of statins on cardiovascular events. “These are very tangible, very profound effects,” Vedhara says.

Similar results have also been seen in young people: A 2018 study of 83 undergraduates found that people with a positive affect — feelings of happiness and positivity — had better antibody responses to a vaccination. Affects, or observable emotions, are impacted by stress, both for better and worse.

One study found that people who had a negative affect in response to daily stressors over the course of a week — meaning they don’t recover well from daily stress — had poorer physical health in the long term. Another study of 8,542 participants found that a positive affect not only helped reduce the damaging effects of stress but was also associated with lower mortality rates. Further research is needed into what actually causes these differences. It may be for both behavioral and neurobiological reasons; when stressed, people might behave in ways that hurt the immune system, such as by drinking alcohol or not getting enough sleep.

But stress also influences the concentration of many hormones, including cortisol, that impact the production of antibodies. During the fight-or-flight response, the brain activates a network that includes the pituitary and adrenal glands. These glands release cortisol and other hormones that keep the body on high alert. But cortisol also turns out to have a surprising place in the immune system: Most immune cells also have a receptor for it. “This means there’s a direct mechanism by which cortisol can regulate immune cells and our immune system,” Vedhara says.

When people have chronically high levels of cortisol from being stressed, they end up with lots of inflammatory cytokines. High levels of cytokines have also been noted in severe cases of Covid-19, as have lower levels of lymphocytes, the white blood cells that help fight infections.

Scientists are looking for other direct relationships between chronic stress and Covid-19. Besides cortisol, other important hormones, including one called Ang-II, are ; Elevated levels of Ang-II have already been associated with severe Covid-19 cases.

Stress is distributed unequally — and for many, it’s exacerbated by systemic racism

Although most of us have experienced more stress this year, chronic stress, like so much else, tends to affect some individuals, like people of color, more than others.

In April, during the early stages of Covid-19, Vedhara found that Black, Asian, and other ethnic minorities in the UK reported feeling more stressed than white people, even after accounting for age, gender, and working situation. These same communities also reported disproportionate deaths from Covid-19.

According to CDC data, Blacks, Native Americans, and Latinos all have age-adjusted hospitalization rates around 4.7 times higher than the rate of white people. A Black person with Covid-19 is almost four times more likely than a white person to die from it.

Goler Blount says it’s frustrating that the data is often reported without context. “It’s not because they’re Black, it’s because of the experience of being Black,” Goler Blount says.

“Discrimination doesn’t stay in the realm of mental health,” says Anderson. “We can actually measure the physical impact on the body.” In the 1990s, public health researcher Arline Geronimus studied what the experience of racism does to the body and found that “racial inequalities not explained by poverty existed across a range of biological systems.” She called the health consequences of the large and small stresses caused by racism “weathering” — and this kind of erosion is more than a metaphor.

Multiple studies show that an experience of discrimination increases cortisol levels, and the effects accumulate over a lifetime.

Chronic stress can start damaging health and affecting gene expression even before birth. A number of studies have linked stress with shorter telomeres, a protective casing at the end of DNA strands that is diminished each time a cell divides. Shortened telomeres have been linked to increased disease and shorter lifespan.

Though telomeres can be repaired by an enzyme called telomerase, stress and cortisol exposure reduces the body’s supply of the enzyme. One study found that the higher a mother’s prenatal anxiety, the shorter her baby’s telomeres were, raising questions about whether stress risks can be inherited. If true, this might amplify the disproportionate effect chronic stress has on people of color.

Another line of research has shown that if young people experience systemic discrimination, it can trigger higher levels of cytokines, magnifying the impact of future stress on their health. A study by the Yale School of Public Health found that by middle age, women who had frequent experiences with discrimination had significantly higher levels of visceral fat, putting them at higher risk for serious conditions such as heart disease and diabetes (two risk factors for severe Covid-19). In older adults, stress changes the levels of hormones involved with blood pressure and contribute to hypertension, another risk factor for Covid-19.

It’s not just the experience of discrimination, but also the fear and anticipation of racism that cause harm. “The vigilance, the concern itself is a strain on the body,” says Brenda Major, a professor and social psychologist at the University of California Santa Barbara. She says the recent videos and other coverage of police killings and protests against police brutality are themselves a source of stress. “Reading about people like you being shot and killed can itself heighten concern, fear, and vigilance,” says Major.

UCSF’s Braveman says chronic stress is also structural, tied to “how we track people into unhealthy places and expose them to unhealthy conditions over their lifetimes.” She says the US culture perpetuates racism — and its stress — even when there is not a particular individual intending to discriminate.

We don’t have to look far for examples of how communities of color are disproportionately exposed to environmental pollutants like cancer-causing chemicals and fine particulate matter that can cause respiratory illnesses, as well as a higher risk of natural disasters —environments that are often sources of stress themselves, as well as an indirect stress when friends and family become ill. “This is literally the environmental impact on us, and it’s how our bodies are responding,” says Goler Blount.

How to leverage what we know about stress to decrease it — and Covid-19 risk

To better understand how stress — both recent and long-term — might be impacting individuals’ risk for Covid-19, many researchers are conducting experiments.

Following up on her April survey of almost 4,000 people in the UK and New Zealand, Vedhara is now asking participants to send in a small hair sample. She’ll use this to measure cortisol, investigating how self-reported mental health over the course of the pandemic results in measurable physical changes. She’ll also look to see whether cortisol levels are associated with being infected with Covid-19 — and the severity of illness.

Already, other research suggests that cortisol is tied to worse Covid-19 outcomes. In a recent study of 535 people published in The Lancet those with confirmed cases of Covid-19 had much higher levels of cortisol than those who did not. After taking measurements within 48 hours of being admitted to the hospital, the scientists found that a doubling of cortisol concentration was associated with a 42 percent increase in mortality.

More research is needed, but in the meantime, Vedhara notes that while the known risk factors for severe Covid-19 cases — age, ethnicity, and preexisting conditions — are largely out of our control, there are ways to improve mental health. We don’t know yet how much reducing stress might help protect against severe Covid-19, but there may be measures that can be used now to reduce anxiety overall.

Understanding the source of stress can be helpful in figuring out how to manage it. “The first step is to understand what is giving rise to those negative feelings,” Vedhara says. Some stress is emotion-focused — like the ongoing uncertainty of when the pandemic will end — and can be reduced through skills like mindfulness. For instance, when patients with colorectal cancer meditated at the beginning of chemotherapy treatments, it improved their cortisol response.

But changing personal behavior cannot combat structural sources of stress. (Meditation is certainly not a cure for the stress of systemic discrimination.)

“One of the most striking features of [self-reported stress in April],” Vedhara says, is that it was strongly related to “how much people were worried about contracting Covid-19.”

A recent study suggests the high numbers of Black, Latinx, and Asian people dying from Covid-19 might actually be an underestimate. Goler Blount says a Black Women’s Health Imperative analysis found that in the next three years, every Black person in the US will lose someone they know to Covid-19 or its long-term consequences. Vedhara suggests this demonstrates a need for more effective public health interventions, rather than psychological ones.

As the pandemic continues to take thousands of American lives each day — and as other economic, safety, and logistical stresses mount — Goler Blount says stress is only accumulating. “All these things are connected. We are here, all in the middle of this, grieving.”

Lois Parshley is a freelance investigative journalist. Follow her Covid-19 reporting on Twitter @loisparshley.

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