Disease tolerance

The body's innate immunity prevents pathogens from taking over by:

• Stopping the pathogen from multiplying
• Killing the pathogen
• Clearing the body of infectious debris

Disease tolerance is the body's ability to contain or limit the impact of foreign invaders attacking the body. In people with tolerance to a particular infection, their body's inbuilt immune system controls the negative effects of infection despite a high load of the pathogen in their body.

Read more: Viral load

A study on disease tolerance published in the scientific journal Nature Reviews Immunology in 2017 explained that tolerance relies on the tissue damage control mechanisms of the human body, which are dependent on the stress and damage signals sent when there is an invasion by a pathogen.

Various signals activate the immune system once the body senses that a pathogen has invaded it. The immune system sends an army of white blood cells that are responsible for launching the correct defence against the pathogen. This is the conventional immune response.

Read more: Immune system can identify COVID-19 because of common cold-causing coronaviruses

In people with tolerance to an infection, the body's tissue damage control mechanism kicks into gear to protect organs and tissues from extensive damage, without dislodging the pathogen from the body.

The body's immune system develops over time: we need to become infected to be able to sense, recognise and fight off pathogens (this is called acquired immunity). But the body's tissue damage control mechanism that copes with the attack on the healthy tissues of the body, or the disease tolerance of the body, prevents or limits the harm done to the body.

Read more: Herd immunity

Although it doesn’t have a direct effect on killing off pathogens, disease tolerance is key until the body’s immune response kicks in. Disease tolerance, thus, is an important aspect in an individual's overall immunity as it preserves the functioning of the affected tissues and organs of the body, while limiting the damage caused by the infection.

Disease tolerance and disease resistance are two fundamentally different functions of the body's immunity. In an article published in the journal Ecology and Evolution, the authors explain resistance as the ability of the body to reduce the risk of infection by controlling the replication or reproduction of the pathogen in the host's body.

Disease tolerance does not limit or strangle the pathogen and stop it from replicating in any way. Instead, it limits or contains the severity of the disease or infection by the pathogen. So, while disease tolerance merely cannot eliminate the foreign invader, it protects the body from extensive damage by the pathogen.

However, one of the drawbacks of disease tolerance is that it cannot have a direct impact on the burden of the pathogen already residing in the body. As a result, various pathogens, which are constantly evolving and mutating, and have ways to dodge the body's immune mechanism, can continue to live and cause damage later.

Disease resistance and disease tolerance are not mutually exclusive. Though they are equally critical in the body's immune response, disease resistance has been well researched and documented over the years while the mechanism of disease tolerance hasn't been studied as much.

Experts in the field have also called for more research to be dedicated towards disease tolerance, as it can be critical in understanding how this tolerance could also be key towards developing more effective treatment strategies for infectious diseases.

As the world continues to battle the COVID-19 pandemic that has affected more than 25 million people and led to more than 850,000 deaths globally, there have also been stories about people getting infected with the new coronavirus infection, and recovering from it without requiring urgent or elaborate medical attention.

Read more: T cells help where antibodies don’t in COVID-19

This innate ability of some people to fight off a deadly infection has called for more studies to be done to understand how disease resistance and disease tolerance have worked in the case of this viral infection caused by the SARS-CoV-2 virus, even as the scientific community continues to work on antivirals and vaccine programmes to tackle it.

An article published earlier this year in Science Advances argues that some antiviral development against COVID-19 has focused on blocking some of the components of the innate immune system for it to work more effectively, but it puts the patient at a higher risk of suffering from secondary infections, as well as complications as a result of the blocked immune response. 

Therefore, disease tolerance is critical in the development of antiviral therapies that can prevent or preserve physiological function, as well as develop disease tolerance drugs that can continue to promote physiological function even in the face of a disease or attack from a pathogen.

The author also suggests a deeper study into disease tolerance by also taking into account people who have been asymptomatic carriers of COVID-19 as well as those who only developed mild symptoms of the disease and recovered quickly as a result. This essentially means studying the body's innate immune response, disease resistance and disease tolerance more deeply than focusing attention on an unknown virus and how it interacts with the body's tissues.

Read more: Severe versus mild symptoms of COVID-19