What Does an Autoinflammatory Disease Have In Common With COVID-19?

What is rheumatoid arthritis?

Rheumatoid arthritis is a long-term disease that mainly affects the joints. It manifests by overall tiredness alongside swelling and stiffness of joints that can be very painful. Exactly what causes rheumatoid arthritis remains unknown. It seems to be influenced by both our genetics and the environment that we live in, including smoking habits, pollution, or our diet. It is an autoinflammatory condition wherein our own immune system gets out of control and attacks our own bodies. Anti-rheumatoid drugs usually target components of the immune system to suppress it and keep it under control. So, what can this autoinflammatory disease have in common with COVID-19? Can we somehow use knowledge gained by the arthritis research in the current pandemic?

Rheumatoid arthritis and COVID-19

COVID-19 is a viral infection caused by the virus SARS-CoV-2. When we become infected, we need a good immune response to be able to fight the virus. However, the immune system of some patients over-reacts to the virus, gets out of control, and starts causing damage. Why some patients react to the virus in this way, we still do not know. Similarly, we do not know the precise triggers of rheumatoid arthritis. So, can rheumatoid arthritis and COVID-19 have something more in common?

Immune cells are a very diverse population, which means that even within the same organ (such as lungs), the same subtype of immune cells can perform different functions. Scientists often use computational methods to distinguish these cells from each other and predict their functions. One such method (called single-cell RNA sequencing) can identify which genes an individual cell expresses to identify what role this cell has within the organ. Genes need to be expressed first in order to be made into proteins which then confer the function of the cell. By this method, scientists recently predicted different types of macrophages (type of immune cells) within the joints that are associated with active arthritis and even seem to cause inflammation in arthritis. When they studied patients with suppressed arthritic symptoms, they were able to also identify a population of macrophages that seemed to be protective against active arthritis.

Interestingly, these different macrophage populations were found to have counterparts in lungs. Lung macrophages similar to the knee macrophages that induce inflammation in arthritis, are associated with increased inflammation and are more abundant in lungs of severe COVID-19 patients. Similarly, healthy lungs seem to have a more abundant population of macrophages that are similar to those that are found in patients with suppressed arthritic symptoms.  Therefore, some macrophages seem to be associated with uncontrolled inflammation in both diseases. And some seem to be connected with protection against our own uncontrolled immune system in both rheumatoid arthritis and COVID-19. Can we somehow use this knowledge to improve the treatment of COVID-19?

Can we take advantage of rheumatoid arthritis to better understand COVID-19?

The answer is: maybe. When we become ill with COVID-19, we need a well-functioning immune system to act against the virus, however, this response in certain patients gets out of control and starts causing further damage. Autoinflammatory conditions such as rheumatoid arthritis which are caused by the lack of regulation of the immune system can therefore have a lot in common with it. Similarly, that is the reason why many drugs that show potential in COVID-19 are also used as anti-rheumatoid drugs that keep arthritic symptoms under control. One such example is dexamethasone, a drug used for the treatment of arthritic flares, which recently also showed potential for treatment of severe COVID-19 patients. Other types of drugs used in arthritis, often with tongue-twisting names such as Tocilizumab, showed potential for COVID-19 treatment as well. These drugs directly bind mediators that travel between cells and induce inflammation to effectively suppress their function to put the immune system back under control.

In conclusion, over-reactivity of the immune response is the cause of both rheumatoid arthritis and severe COVID-19. Therefore, using the knowledge gained from rheumatoid arthritis research can prove to yield beneficial results even in the COVID-19 research.

Original Paper: https://www.biorxiv.org/content/10.1101/2020.07.26.221572v1

Oximmuno summary for researchers: 

https://www.immunology.ox.ac.uk/covid-19/covid-19-immunology-literature-reviews/covid-19-and-rheumatoid-arthritis-share-myeloid-pathogenic-and-resolving-pathways

These summaries were created by the OxImmuno Literature initiative and are simplified views which are meant to help to explain the concept/ideas behind the research papers and not every single detail.  They should not be considered as an endorsement or otherwise of the research.  For more information on the initiative and its work please see our first blog post.