Detecting Auto-Antibodies for Early Identification of High-Risk COVID-19 Cases

Researchers recently discovered that some COVID-19 patients have auto-antibodies against type 1 interferons, which are crucial immunological signaling proteins. To investigate this further, they conducted an in-depth study on 123 Japanese COVID-19 patients to determine how common these auto-antibodies are in severe cases and their impact on the immune system.

Their results may provide insight into how auto-antibodies exacerbate the severity of COVID-19.

While most COVID-19 patients experience mild to moderate symptoms with brief illness duration, some experience exceedingly severe symptoms; in the worst cases, these patients pass away from complications, including thrombosis or respiratory failure.

It is commonly known that susceptibility to severe COVID-19 is increased by age and underlying medical problems such as diabetes or immunodeficiencies. Nonetheless, some people continue to have significant COVID-19 for no obvious cause.

Auto-antibodies, or antibodies that mistakenly target particular proteins made by one's body, could be one explanation. Under normal conditions, the body's defense against viral infections is greatly aided by type I interferons, often known as “t1-IFNs,” which obstruct viral replication and aid in immune system mobilization.

Auto-antibodies against t1-IFNs, on the other hand, can nullify their action and weaken the body's defenses. Although it was rare to find these auto-antibodies before COVID-19, there have been numerous reports of severe COVID-19 patients having them once the pandemic began. Is the prevalence of auto-antibodies against t1-IFNs higher than previously believed?

To determine whether and how auto-antibodies targeting t1-IFNs are associated with COVID-19 severity, a study team comprising Chiaki Iwamura, a Lecturer at Chiba University in Japan, examined blood samples from 123 Japanese patients. The research was published in the Journal of Clinical Immunology. Drs. Kiyoshi Hirahara and Koutaro Yokote from Chiba University and Ami Aoki from Niigata University co-authored this study.

Before confirming whether the auto-antibodies could successfully neutralize t1-IFNs in cell cultures, the researchers used an enzyme immunoassay to find auto-antibodies to t1-IFNs in the blood samples.

We found that three out of 19 severe and four out of 42 critical COVID-19 patients had neutralizing auto-antibodies to t1-IFNs. Interestingly, there were no characteristic clinical features among patients with auto-antibodies to t1-IFNs.”

Chiaki Iwamura, Lecturer, Chiba University

There were no pointers in the data regarding why some COVID-19 patients developed these auto-antibodies, even when considering previous infections, treatments received, and underlying immune disorders.

Based on these findings, it is difficult to estimate the presence of auto-antibodies to t1-IFNs from the usual blood tests and clinical background.”

Chiaki Iwamura, Lecturer, Chiba University

The researchers next carried out RNA sequencing and B cell receptor analysis to provide some insight into how auto-antibodies to t1-IFNs affected COVID-19 patients. These studies demonstrated that two types of white blood cells, canonical monocytes, and conventional dendritic cells, displayed reduced IFN signaling for patients with auto-antibodies.

Furthermore, these patients' B cells, another subset of immune cells, had fewer SARS-CoV-2-specific receptors, suggesting a decreased capacity to fight infection.

All things considered, these results emphasize how critical it is to examine auto-antibodies to t1-IFNs in greater depth when dealing with viral epidemics.

People with auto-antibodies 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, thus, we hope to collaborate with companies to develop a system to detect auto-antibodies to t1-IFNs in the blood. Ideally, we would develop a test to examine the presence of these auto-antibodies in regular health checkups so that people will be able to know whether they have them with little burden.”

Chiaki Iwamura, Lecturer, Chiba University