Decades of research on autoimmune diseases may help to determine who has the highest risk of severe illness or death from COVID-19.
If two people who seem similar in all respects become infected with SARS-CoV-2, one may have no symptoms and the other may end up in the hospital with a serious lung infection.
COVID-19 has caused researchers around the world to scratch their heads because they do not fully understand why some people who seem completely healthy experience severe illness and others do not.
Now an international team of researchers has suggested that experience with autoimmune diseases may improve understanding of why people respond differently to COVID-19.
Decades of research on autoimmune diseases have provided a good sense of how the immune system works, and this might be used to determine whether people who have autoimmune diseases or are predisposed to developing them are more or less susceptible to COVID-19 and whether this knowledge can be used to treat them more effectively.
“The immune system goes haywire in both autoimmune diseases and COVID-19, and this response causes the symptoms and determines the severity of illness. We therefore believe that we can learn a lot about the differences in how the body responds to COVID-19 by examining what we already know about autoimmune diseases,” explains a researcher behind a perspective article published in Frontiers in Immunology, Tugce Karaderi, Assistant Professor, Center for Health Data Science, University of Copenhagen.
COVID-19 and autoimmune diseases have many similarities
According to Tugce Karaderi and her colleagues, we should use our knowledge on autoimmune diseases to understand COVID-19 because of the similarities between these otherwise very different diseases.
COVID-19 is caused by the SARS coronavirus 2, whereas autoimmune diseases are caused by the body’s immune system considering the body’s own cells and organs to be foreign matter that needs to be eliminated.
Nevertheless, these diseases have some similarities.
The symptoms of autoimmune diseases result from an overactive immune response.
The same applies to COVID-19. The severe cases do not result from the infection itself but because the immune system creates a cytokine storm, producing many more immune cells than necessary.
The immune system thus attacks both the virus and the body.
“This similarity between autoimmune diseases and COVID-19 is interesting and supports the view that we can improve our understanding of why different individuals respond differently to COVID-19 by applying the knowledge we have gathered on autoimmune diseases over the years,” says Tugce Karaderi.
Gene variants determine the risk of severe disease
Specifically, Tugce Karaderi and her colleagues focus on whether some of the same biological mechanisms apply when the immune system goes haywire and does more harm to the body than good.
They suggest that examining the biological or the genetic risk factors for developing autoimmune diseases might also enable some of these to be identified as being risk factors for severe illness or death from COVID-19.
In their article, the researchers also suggest several genes worth investigating to identify the biological link between autoimmune diseases and the immune response to SARS-CoV-2 that could potentially be used as a key to understand why individuals respond differently to SARS-CoV-2 infection. These include toll-like receptor 7 (TLR7), a known pathogen-sensing receptor that has been shown to play a role in autoimmune diseases and is also among the initial innate immune cell receptors that sense SARS-CoV-2.
“We know of two sets of brothers from different families who had their own variant of TLR7 and all developed COVID-19. Young people rarely get severely ill, but these four brothers did,” explains Tugce Karaderi.
Drugs for autoimmune diseases may be effective against COVID-19
In addition, greater insight into the mechanisms by which some people become severely ill from COVID-19 can also be used to identify additional targets for treatment and drug repurposing.
An example is dexamethasone, an anti-inflammatory drug used to treat autoimmune conditions such as arthritis and that has also been shown to have a good effect in reducing mortality among people with severe or critical COVID-19 requiring ventilation or respiratory support.
“Individuals with autoimmune diseases are treated with various drugs that suppress the immune system so that it does not overreact inappropriately. There has been some discussion about whether suppressing the immune system can increase the risk of severe COVID-19 or whether these drugs keep the immune system of individuals with COVID-19 from going haywire,” says Tugce Karaderi.
She elaborates that trials are already underway to investigate the effectiveness of using these drugs normally used to treat individuals with autoimmune diseases to treat the individuals with COVID-19 who do not necessarily have an autoimmune disease.
Data waiting to be reviewed
Tugce Karaderi and her colleagues suggest several scientific initiatives that may advance knowledge on COVID-19 and hopefully counteract the severe illness among individuals at higher risk.
The researchers think that it should be investigated further whether individuals with autoimmune diseases or susceptibility to autoimmune diseases (such as with a family history of autoimmune diseases) have an increased risk of severe disease progression with COVID-19. The studies must be based on large data sets that compare the risk of developing severe illness between individuals with and without autoimmune diseases or a family history of autoimmune diseases while considering other factors, such as female or male sex or the medication use.
It should also be investigated at a larger scale whether genes associated with the risk of developing autoimmune diseases also affect the risk of a severe disease trajectory in COVID-19. There have been such studies in the past year, and larger ones are now on the way. These genome-wide association studies can advance our understanding of the mechanisms that affect the severity of COVID-19. Existing knowledge about autoimmune diseases can significantly contribute to and support the biological interpretation and clinical use of the results from these genome-wide association studies to help people with severe COVID-19.
“We already have access to a huge quantity of data, which is waiting to be investigated to improve our understanding of COVID-19, and the link between susceptibility to autoimmune diseases and severity of COVID-19 progression,” concludes Tugce Karaderi.
