Symptoms that range from mild to serious can occur in people infected with the novel coronavirus. Two recent analyses show that certain life-threatening cases can be attributed to weak points in the immune systems of patients.
At least 3.5 percent of patients with serious, novel coronavirus-induced COVID-19 disease have gene mutations involved in antiviral protection. And at least 10 percent of patients with serious illness, instead of battling the virus, produce ‘auto-antibodies’ that strike the immune system. The findings were announced on September 24, 2020, in two articles in the journal Science.
For diagnostics and care, the thesis has immediate consequences. When anyone tests positive for the virus, auto-antibodies should certainly be screened, too, with medical follow-up if such tests are positive. The elimination of such antibodies from the blood will likely relieve the symptoms of the disease.
The aim was to examine the genomes of the patients — in particular, a group of 13 genes involved in influenza interferon immunity. Interferon molecules serve as the body’s defense mechanism in healthy individuals. They sense viruses and bacteria entering and sound the alarm, which brings to the scene, other resistant defenders.
Casanova’s team has previously identified genetic mutations that inhibit the development and function of interferon. People with these mutations, including those which cause influenza, are more susceptible to certain pathogens. The team thought that identifying similar mutations in individuals with COVID-19 could help physicians recognize patients at risk of developing extreme forms of the disease. It may also point to new treatment paths.
When researchers started studying patient samples, young and old people began to discover dangerous mutations. The team found that 23 of the 659 analyzed patients had flaws in the genes involved in the synthesis of antiviral interferons.
Without a complete package of these antiviral defenders, the researchers believed, COVID-19 patients will not be able to fight off the virus. A new idea ignited thinking. Maybe interferons were also absent in other patients with extreme COVID-19 — but for another cause. Maybe the bodies of certain patients have damaged these molecules themselves. Some patients could make antibodies that attack the body, as in autoimmune disorders such as type 1 diabetes and rheumatoid arthritis.
The team’s study of 987 life-threatening COVID-19 patients showed only that. Of the patients, at least 101 had auto-antibodies to an array of interferon proteins. The researchers discovered that these antibodies prevented interferon activity and were not present in patients with mild COVID-19 cases.
The team’s new work could change how doctors and health officials think about vaccine delivery plans, and even future therapies, by looking ahead clinically. For example, a clinical trial might investigate whether infected individuals who have auto-antibodies gain from medication with one of the 17 auto-antibodies-neutralized interferons or with plasmapheresis, a medical procedure that eliminates the antibodies from the blood of patients. The influence of these harmful antibodies may theoretically be counteracted by either process.