Recently, researchers have discovered that some individuals who have had COVID-19 possess auto-antibodies that target their own type 1 interferons, which are essential proteins for immune signaling.
To further explore the prevalence of these auto-antibodies in severe COVID-19 cases and their impact on the immune system, scientists conducted a comprehensive study involving 123 Japanese COVID-19 patients. The findings from this research may provide insights into how auto-antibodies contribute to the severity of COVID-19.
While most people experience mild and short-lived symptoms from COVID-19, some individuals develop severe symptoms, which can even lead to fatalities due to complications like respiratory failure or blood clots. Factors such as age and underlying health conditions like diabetes or weakened immune systems are known to increase the risk of severe COVID-19. However, in some cases, severe illness occurs without any identifiable cause.
One possible explanation for this severe manifestation could be the presence of auto-antibodies, which are antibodies that mistakenly target the body’s own proteins. Type I interferons (t1-IFNs) are crucial for fighting viral infections as they help impede viral replication and activate the immune response. However, auto-antibodies against t1-IFNs can counteract their functions, weakening the body’s defense mechanisms. While auto-antibodies targeting t1-IFNs were rarely detected before the COVID-19 pandemic, numerous reports have surfaced of severe COVID-19 patients exhibiting these auto-antibodies. This raises the question of whether such auto-antibodies are more prevalent than previously known.
In an attempt to address this question, a team of researchers led by Lecturer Chiaki Iwamura from Chiba University, Japan, investigated the relationship between auto-antibodies targeting t1-IFNs and COVID-19 severity by studying blood samples from 123 Japanese patients. Their findings were published in Volume 44 of the Journal of Clinical Immunology on April 22, 2024. The study was co-authored by Dr. Kiyoshi Hirahara, Dr. Koutaro Yokote from Chiba University, and Dr. Ami Aoki from Niigata University.
The researchers initially used an enzyme immunoassay to detect auto-antibodies against t1-IFNs in the blood samples, followed by confirming whether these antibodies could effectively neutralize t1-IFNs in cell cultures. Dr. Iwamura stated, “We observed that three out of 19 severe and four out of 42 critical COVID-19 patients had neutralizing auto-antibodies against t1-IFNs. Interestingly, no specific clinical characteristics were identified among patients with these auto-antibodies.” This suggests that there are no clear indicators explaining why certain COVID-19 patients develop these auto-antibodies, despite considerations of prior infections, treatments received, and underlying immune conditions. Dr. Iwamura pointed out, “Based on these results, assessing the presence of auto-antibodies to t1-IFNs using routine blood tests and medical history is challenging.”
To gain insights into how auto-antibodies against t1-IFNs impact COVID-19 patients, the researchers conducted RNA sequencing and B cell receptor analyses. These examinations revealed that conventional dendritic cells and canonical monocytes, two types of white blood cells, experienced weakened IFN signaling in patients with auto-antibodies. Additionally, B cells in these patients exhibited fewer SARS-CoV-2-specific receptors, suggesting reduced efficacy in combating infections.
Overall, these findings underscore the importance of scrutinizing auto-antibodies against t1-IFNs in times of viral outbreaks. Dr. Iwamura cautioned, “Individuals with auto-antibodies against t1-IFNs are not only more vulnerable to SARS-CoV-2 but also to common viruses like influenza and potentially new viruses that may emerge in the future.” As a result, the researchers aim to collaborate with companies in developing a system for detecting these auto-antibodies in routine health screenings. The goal is to enable individuals to determine their auto-antibody status with minimal inconvenience.
It is hoped that their efforts will materialize soon, enhancing our ability to diagnose, prevent, and combat viral infections effectively.
