Columbia U researchers make interesting case that the most severe Covid-19 cases are brought on by flaws in one of the most ancient parts of the immune response, the “Complement” system.
One of the immune system's oldest branches, called complement, may be influencing the severity of COVID-19 disease, according to a new study from researchers at Columbia University Irving Medical Center.
Among other findings linking complement to COVID, the researchers found that people with age-related macular degeneration—a disorder caused by overactive complement—are at greater risk of developing severe complications and dying from COVID.
The connection with complement suggests that existing drugs that inhibit the complement system could help treat patients with severe disease. The authors also found evidence that clotting activity is linked to COVID severity and that mutations in certain complement and coagulation genes are associated with hospitalization of COVID patients. ...snip... Coronaviruses, the survey found, are masters of mimicry, particularly with proteins involved in coagulation and proteins that make up complement, one of the oldest branches of the human immune system.
Complement proteins work a bit like antibodies and help eliminate pathogens by sticking to viruses and bacteria and marking them for destruction. Complement can also increase coagulation and inflammation in the body. "Unchecked, these systems can also be quite detrimental," says Shapira.
"The new coronavirus—by mimicking complement or coagulation proteins—might drive both systems into a hyperactive state." ...snip... That led Shapira and Tatonetti to look at COVID patients with macular degeneration, an eye disease caused by overactive complement, as well as common coagulation disorders like thrombosis and hemorrhage.
Among 11,000 COVID patients who came to Columbia University Irving Medical Center with suspected COVID-19, the researchers found that over 25% of those with age-related macular degeneration died, compared to the average mortality rate of 8.5%, and roughly 20% required intubation. The greater mortality and intubation rates could not be explained by differences in the age or sex of the patients.
"Complement is also more active in obesity and diabetes," Shapira says, "and may help explain, at least in part, why people with those conditions also have a greater mortality risk from COVID."