Complement system may increase the severity of COVID-19 disease

The complement system is one of the oldest branches of the immune system plays a crucial role in the severity of COVID disease according to a new study. The researchers from Columbia University Irving Medical Center conducted this study. Nature Medicine published this study on August 3.

The researchers found that people with age-related macular degeneration are at higher risk of developing severe complications and dying from COVID-19 disease. The overactive complement system is responsible for causing macular degeneration. This connection suggests that existing drugs that inhibit the complement system could help to treat patients with severe disease.


How the complement system related to COVID-19?

The researchers also found that clotting activity is linked to COVID severity. Moreover, the mutations in specific complement and coagulation genes are associated with the hospitalisation of COVID patients.

Sagi Shapira, Ph.D., MPH, is a professor who led the study along with Nicholas Tatonetti, Ph.D., Professor at Columbia University Vagelos College of Physicians and Surgeons. They said that these results provide valuable insights into the pathophysiology of COVID-19. It helps to find the role of complement and coagulation pathways in determining clinical outcomes of patients infected with SARS-CoV-2.

Sagi Shapira
Sagi Shapira
Nicholas Tatonetti
Nicholas Tatonetti

Role of the complement system in the body

Shapira says that viruses have proteins that can mimic specific proteins in host to trick the host’s cells in aiding the virus with completing its life cycle. He also said that based on their previous work and the work of others, they suspected that identifying those mimics could provide clues about how viruses cause disease.

The survey found that coronaviruses are masters of mimicry, particularly with proteins involved in coagulation and complement system. Moreover, the complement proteins work a bit like antibodies. It eliminates pathogens by sticking to viruses and bacteria and making them for destruction. Furthermore, it can also increase coagulation and inflammation in the body. Shapira says that these systems can also be quite detrimental. He also added that the coronavirus might drive both the systems into a hyperactive state.


Macular degeneration associated with COVID mortality

The complement and coagulation system has a significant influence on COVID severity. Following this, people with pre-existing hyperactive coagulation or complement disorders should be more susceptible to the virus. So, Shapira and Tatonetti decided to look at COVID patients with macular degeneration. And also the common complications of coagulation like thrombosis and bleeding (hemorrhage).

Among 11,000 COVID patients at Columbia University Irving Medical Center, the researchers found that over 25% of those with macular degeneration died, compared to an average mortality rate of 8.5% and roughly 20% required intubation. Furthermore, the differences between the age or sex of the patients could not determine the higher mortality and intubation rates.

Shapira says that complement is also more active in people with obesity and diabetes. It also explains why people with those conditions also have a higher mortality risk of COVID. Moreover, people with coagulation disorders also were at increased risk of mortality from COVID.


How coagulation and complement pathways activated?

Tatonetti says that they found that the complement pathway expressed differently in SARS-CoV-2 infected patients. The complement system in COVID cases is overactive in similarity to other infections like flu. More evidence related to severe COVID with coagulation and complement comes from genetic analysis of thousands of patients from the U.K. Biobank. This evidence contains a lot of medical records and genetic data on half a million people.

Shapira says that, however, these variants are not going to determine someone’s outcome. But this finding provides another line of evidence of how coagulation and complement pathways involved in morbidity and mortality of COVID-19.

Tatonetti hopefully says that their findings provide a stronger foundation for the idea that coagulation and complement plays a role in COVID. This study would inspire others to evaluate this hypothesis and could help find any treatment for this problem.

Check out more information from the article, Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection.”

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