Role of auto-antibodies in severity of COVID-19 revealed

Although COVID-19 manifests as a mild and short-lived illness in most people, some people suffer from extremely severe symptoms; in the worst cases, these patients die due to complications such as respiratory failure or thromboembolism. It is well known that factors such as age and underlying medical conditions such as diabetes or immune deficiency increase vulnerability to severe COVID-19. However, some patients still experience severe COVID-19 for no apparent reason.

A possible explanation may lie in auto-antibodies, which are antibodies that mistakenly target specific proteins produced by one's own body. Under normal circumstances, type I interferons (or 't1-IFNs') play a key role in the body's defence against viral infections; they interfere with viral replication and help activate the immune system. However, auto-antibodies against t1-IFNs can neutralise their activity, thereby compromising the body's defence mechanisms. While detection of these auto-antibodies was uncommon before COVID-19, since the pandemic began there have been several reports of severe COVID-19 patients suffering from them. Could auto-antibodies targeting t1-IFNs be more common than previously thought?

To answer this question, a research team including Chiaki Iwamura, a lecturer at Chiba University in Japan, analysed blood samples from 123 Japanese patients to determine if and how auto-antibodies targeting t1-IFNs relate to the severity of COVID-19. Their findings were published in volume 44 of the journal . Journal of Clinical Immunology on April 22, 2024. The research is co-authored by Dr. Kiyoshi Hirahara and Dr. Kotaro Yokote of Chiba University, as well as Dr. Ami Aoki of Niigata University.

The researchers first conducted enzyme immunoassays to detect autoantibodies to t1-IFNs in blood samples, and then confirmed whether these antibodies could effectively neutralize t1-IFNs in cell culture. “We found that three of 19 severe and four of 42 critical COVID-19 patients had neutralising auto-antibodies to T1-IFN. Interestingly, patients with auto-antibodies to T1-IFN did not have any specific clinical features,” Dr. Iwamura commented. In other words, the data provided no indication as to why these auto-antibodies developed in some COVID-19 patients, even after considering previous infections, treatments received, and underlying immune disorders. “Based on these findings, it is difficult to predict the presence of auto-antibodies to t1-IFNs from routine blood tests and clinical background.” Dr. Iwamura commented.

To shed some light on how auto-antibodies to T1-IFN affected COVID-19 patients, the researchers conducted RNA sequencing and B cell receptor analysis. These experiments showed that conventional dendritic cells and canonical monocytes, two types of white blood cells, displayed weaker IFN signaling in patients in whom auto-antibodies were present. In addition, B cells (another type of immune cell) in these patients had fewer SARS-CoV-2-specific receptors, meaning there was less effectiveness in fighting the infection.

Overall, these findings highlight the importance of looking at auto-antibodies to t1-IFNs in more detail when facing viral pandemics. “People with autoantibodies to T1-IFNs are more susceptible not only to SARS-CoV-2, but also to common viruses such as influenza, and to unknown viruses that may emerge in the future.” Dr. Iwamura warns, “Thus, we hope to collaborate with companies to develop a system to detect auto-antibodies to t1-IFNs in the blood. Ideally, we will develop a test to check for the presence of these auto-antibodies in routine health checkups so that people can know whether they have them or not with less burden.”

Let us hope that his vision becomes a reality soon so that we can be better prepared to diagnose, prevent and fight viral infections.