One study suggests "Long-COVID" may be related to immune signatures, in which past exposure to the virus affects responses to new infections. Patients with PASC had a weak response to SARS-CoV-2 but a stronger response to OC43, another common cold-causing coronavirus. This understanding could provide guidance for future treatment and risk assessment.
Study results identify a potential marker that could help identify people at high risk for Long-COVID.
Many people infected with SARS-CoV-2, the virus that causes COVID-19, experience symptoms that resolve within days or weeks. But for a significant number of people, symptoms last for weeks, months or even years. This is known as post-acute sequelae of COVID-19 (PASC), commonly known as "long COVID." Although several risk factors for PASC have been proposed, we still don't understand what causes the disease or why some people get it and others don't. To further complicate matters, PASC can have different causes in different people.
Some patients with PASC have changes in certain immune responses, suggesting that the occurrence of PASC is related to immune mechanisms. PASC is particularly common in people with systemic autoimmune rheumatic diseases. This is a chronic disease, like lupus, in which the immune system mistakenly targets the body's own tissues, causing inflammation. Up to 45% of rheumatic patients infected with SARS-CoV-2 develop PASC.
Study results and antibody responses
Funded by the National Institutes of Health (NIH) and led by Dr. Zachary Wallace of Massachusetts General Hospital (MGH), Dr. Jeffrey Sparks of Brigham and Women's Hospital (Brigham and Women's Hospital), and Dr. Galit Alter of MGH, MIT, and Harvard, a research team studied the antibody responses of rheumatic patients infected with COVID-19. The research team measured antibody responses to SARS-CoV-2, various other pathogens, and vaccines. They compared the antibody responses of people with PASC and those without PASC. The research results were published in the journal Science Translational Medicine on September 6, 2023.
The team found that people with PASC had a much weaker antibody response to SARS-CoV-2 than people without PASC. However, PASC patients had an increased response to another coronavirus called OC43, an endemic virus that causes common cold-like symptoms. Furthermore, the stronger the PASC patients' response to OC43, the weaker their response to SARS-CoV-2. This suggests that antibodies against OC43 may also respond to SARS-CoV-2. The researchers observed these patterns in two independent groups of more than 40 rheumatic disease patients, about one-third of whom had PASC.
Western blotting and its effects
The findings suggest that PASC may arise from a phenomenon known as immune imprinting. This refers to how a person's history of previous infections affects their immune response to new infections. In this case, when a person who was previously infected with OC43 becomes infected with SARS-CoV-2, part of their immune system's response is to use the antibodies produced when infected with OC43 to recognize SARS-CoV-2. This "recall" response to OC43 contributes to the overall inefficiency of the response to SARS-CoV-2. Further research is needed to determine whether and how this weak immune response leads to PASC.
"With viruses, the body's first exposure to it affects lifelong immunity," Alter explained. "We know that in the case of influenza, previous exposure to viral strains affects a person's immune response to subsequent strains. This concept may also apply to coronaviruses and may affect the risk of Long-COVID, especially in people with rheumatic diseases."
It remains to be seen whether these findings also apply to people without rheumatic disease. But at least in some cases, these results may help explain the pathogenesis of PASC. They also provide clues that could help guide the development of new treatments. Finally, they also propose a marker that could help identify people at high risk for PASC so they can be enrolled in more targeted clinical trials.