COVID-19 and inflammation

Inflammation is a complex interplay of various immune system cells and inflammatory mediators that are specially released in response to various types of irritants - bacterial, viral, protozoans, etc. 

On the outside, inflammation appears as heat, redness and swelling of the affected area along with loss of function. Severe inflammation shows up as fatigue, fever and a general feeling of being sick. This means that your immune system is working overtime to protect your body. Increased metabolism due to fever leads to an increase in the production of antibodies and other immune cells. This is done to clear out the infection quickly.

Microscopic examination of the affected tissue shows:

• Increase in the blood supply in the affected tissue to improve the healing process.
• Irritation of nerves in the area which causes pain and makes the person avoid moving the affected part.
• Increased permeability of the blood vessels which allows infiltration of inflammatory cells at the injury or infection site. This also leads to an increased influx of fluids into the affected tissue - the reason for swelling.
  Increased fluid also occurs due to another protective mechanism in the body - mucous cells.
  Mucous cells are a type of epithelial cells (which occur on surfaces like skin and blood vessels) that are specialised to secrete a substance called mucous - a thin and slippery fluid that keeps your body cavities moist. Increased mucous production is what causes a runny nose.

Viral infections first activate our innate immune system. Innate immunity is a non-specific type of immune reaction that is the first to act whenever our body is exposed to a new infectious organism. These mostly include macrophages - a type of large cells that can engulf pathogens and destroy them.

The cells of the innate immune system then secrete various signalling proteins called cytokines and chemokines, which recruit specialized cells that can fight viruses.

Since viruses are intracellular parasites (live inside healthy cells), they are countered by a mechanism called Th1 type of response. IFN gamma is a specialised cytokine that plays a role in this type of response. It activates the CD8+ cells, which are a type of T cells (a type of lymphocytes - white blood cells) which identify the virus-infected cells and release specific antiviral compounds to kill those cells.

Unlike macrophages, T cells can only kill a specific or only one type of virus. 

Along with killer T cells, the immune system also produced memory T cells, which can help our body to act quickly the next time the same virus attacks.

In other words: when the body detects a foreign object, if this object is new to the body, it triggers the innate immune system. This system sends in its soldiers - macrophages - to eat up the infection-causing pathogen. It also triggers certain T-cells (also part of the immune system) to release antiviral compounds. Once T-cells have fought an infection, they also form a memory of it so that the next time this pathogen attacks the body, the body is better prepared to fight. This is the reason we become immune to some diseases after we've had them once. Example: chickenpox, which is caused by the Varicella-zoster virus.

To prevent the inflammatory cells from causing a lot of damage, our immune system has specific chemical messengers that slow down or downregulate the whole process of inflammation once the pathogen is destroyed.

This process is mediated through the Th2 cytokines. A balance in both Th1 and Th2 processes is required to maintain optimum immune reaction and keep it from going out of hand. Normally, Th2 helps fight extracellular pathogens like bacteria. 

However, researchers have found that apart from this process, lungs also have specialised macrophages that can slow down inflammation and keep acute respiratory diseases from exacerbating. These macrophages are called nerve and airway associated macrophages (NAMs). 

Normally, all organs of our body have specialised macrophages. The ones in our lungs are called alveolar macrophages (AMs) - these are present in alveoli (the air sacs in the lungs). It is these AMs that are responsible for initiating the innate immune response in infections of lungs like SARS-CoV-2 infection (also called COVID-19).

A combination of laboratory and animal-based studies show that depletion of NAMs leads to increased levels of inflammatory agents, and a higher tendency of inflammation to get out of hand. NAMs specifically produce anti-inflammatory cytokines in the body which suppresses inflammatory responses - and may reduce the symptoms of an infection like COVID-19.

These NAMs are being labelled as peacekeeping cells or peacekeeping macrophages.

Read more: 4 inventive treatments for COVID-19

So far, there is no research that says NAMs are being thought of as a candidate for reducing COVID-19 complications. However, considering their function, they may play a role in COVID-19 treatment.

In a clinical study done in Wuhan, IL-6 - which increases inflammation - was found to be high in patients who died of COVID-19.

(IL-6 or interleukin 6 is found to increase inflammation in people suffering from diabetes and rheumatoid arthritis, among other conditions.)

Clinical trials are underway to check the efficiency of IL-6 suppressor drugs in COVID-19 patients. IL-6 inhibitors are already being used for the treatment of rheumatoid arthritis - an inflammatory condition that mostly affects joints.

Read more: What are ACEII receptors and what do they have to do with COVID-19