Wed Oct 19

Being stressed out before you get COVID increases your chances of long COVID. Here's why

Written by: Susannah Tye, Group Leader, Queensland Brain Institute, The University of Queensland

Stress is part and parcel of modern life. When we’re on the verge of a new challenge or a significant event, we can experience stress mixed with excitement and a sense of challenge. This form of “good” stress, or eustress ^[1], is important for growth, development, and achievement.

However, prolonged stress and overwhelming or traumatic events can negatively impact our health. These forms of “bad” stress – or distress – can make us sick, depressed, anxious and over the long term, increase our risk ^[2] of heart disease, stroke, type 2 diabetes, dementia and even cancer ^[3].

Distress can also affect our ability to fully recover ^[4] from COVID. Ongoing symptoms for a month or more is referred to as long COVID. Those affected can experience fatigue, brain fog, shortness of breath, loss of taste and smell, difficulty sleeping, anxiety and/or depression. For some, these symptoms can last for many months or even years, making it impossible to return to pre-COVID life.

In a Harvard University study ^[5] published last month, people suffering psychological distress in the lead up to their COVID infection had a greater chance of experiencing long COVID. The researchers found those with two types of distress (depression, probable anxiety, perceived stress, worry about COVID, and loneliness) had an almost 50% greater risk of long COVID than other participants.

So how might distress impact the body’s ability to fight infection?

First, we need to look at inflammation

Inflammation ^[7] is the body’s way of responding to an infection or injury.

When the immune system ^[8] encounters a virus, for example, it launches an attack to neutralise infected cells and store a memory of that virus so it can respond faster and more effectively the next time.

Many things can cause inflammation, including bacteria and viruses, injuries, toxins and chronic stress.

The body has many different responses to inflammation, including redness, heat, swelling and pain. Some inflammatory responses can occur silently within the body, without any of these typical symptoms. At other times, inflammation can mobilise energy resources to cause exhaustion and fever.

During inflammation, immune cells release substances known as inflammatory mediators. These chemical messengers cause small blood vessels to become wider (dilate), allowing more blood to reach injured or infected tissue to help with the healing process.

This process can also irritate nerves and cause pain signals to be sent to the brain.

What does distress have to do with inflammation?

In the short term, stress causes ^[9] the release of hormones that suppress inflammation, ensuring the body has enough energy resources available to respond an immediate threat.

However, when experienced over an extended period of time, stress itself can cause low grade “silent” inflammation. Chronic distress and related mental health conditions such as anxiety and depression, are all associated with elevated levels of inflammatory mediators. In fact, the repeated exposure to mild, unpredictable stress is enough to elicit an inflammatory response.

Fatigued woman rests her head against a wall

Repeated exposure to stress can produce an inflammatory response. Stacey Garrielle Koenitz Rozells/Unsplash ^[10]

Pre-clinical (lab-based) studies ^[11] have shown chronic mild stress can cause depression-like behaviour by promoting inflammation, including activating immune cells in the brain (microglia). When anti-inflammatories were given during the mild stress exposure they prevented depression-like behaviour. However if given after the event, the anti-inflammatories were ineffective.

When inflammation is ongoing, such as with extended periods of distress, the immune system changes the way it responds by reprogramming the immune cells. Effectively, it switches to “low surveillance mode”. In this way, it remains active throughout the body, but downgrades its responsiveness to new threats.

Because of this, the response may be slower and less effective. Consequently, the process of recovery can take longer. For a virus like COVID, it’s possible that prior exposure to distress may similarly impair the body’s ability to fight the infection and increase the risk of long COVID.

How might distress affect recovery from COVID?

There is still much to learn about how COVID infection affects the body and how psychological factors can impact clinical outcomes in the short and long term.

COVID has far-reaching effects across multiple body systems, affecting the lungs and heart to the greatest degree, and increasing the risk of blood clotting and stroke.

Because the virus resides within human cells, an immune system switched to “low surveillance mode” as a result of psychological distress may miss early opportunities to destroy infected tissues. The virus can then gain an advantage over the defence (immune) system.

Conversely, distress can suppress the early response, tipping the balance in favour of the invader.

An immune system already switched to low surveillance mode might miss early opportunities to destroy the virus. Whoislimos/Unsplash ^[13]

So what can we do about it?

Vaccines work by helping to train the immune system to find the target sooner, giving the immune system the advantage.

Behavioural interventions that improve the ability to cope with stress decrease inflammation ^[14] and may help to enhance the immune response to COVID.

It’s also important to be aware that exposure to COVID increases the risk ^[15] of depression, anxiety or other mental health conditions. Knowledge of this two-directional link is the first critical step to improving clinical outcomes.

A lifestyle medicine approach that helps to reduce levels of distress and address mental health symptoms has important downstream benefits for physical health. This is likely to not only be the result of direct effects on the immune system itself, but also through related improvements in health behaviours ^[16] such as diet, exercise and/or sleep.

Further research is needed to better understand the impact of distress on the immune system, mental health and COVID outcomes, and to highlight ways to intervene to prevent long COVID and support recovery.