Since the start of the COVID-19 pandemic, which was caused by a virus known as SARS-CoV-2, there have been almost 800 million confirmed cases and 7 million deaths. It’s thought that about 10% of those who were infected (and survived) went on to develop long COVID, also known as post-COVID syndrome. This disorder is highly variable and consists of a huge range of symptoms including but not limited to brain fog, fatigue, fever, gastrointestinal distress, sleep disturbances, and muscle or joint pain.
For years, researchers have been trying to determine the cause (or causes) of long COVID, which still affects many people. Some research has suggested that problems in the gut microbiome may be to blame, other studies have found that persistent infection from the virus itself may be involved. But there has been a lot of evidence that immunological and inflammatory problems are connected to long COVID.
A new study published in Cell Reports Medicine has determined that long COVID may be due to antibodies that erroneously attack the body’s own tissues, known as autoantibodies. These autoantibodies may play a major part in the development of long COVID.
In this study, the researchers collected samples from 34 long COVID patients, and isolated one of the major classes of antibodies, called IgGs (immunoglobulin Gs) from the samples. The IgGs were then injected into a mouse model. The investigators saw that the mice then became hypersensitive to pain for at least two weeks after injection. The same results were seen when mice were injected with IgGs that had been isolated from the same patients’ blood samples, taken two years later.
"This finding suggests that the underlying disease mechanism may persist long after the initial infection, potentially explaining why many patients experience long-term symptoms,” said co-senior study author Niels Eijkelkamp, Ph.D., a Professor at UMC Utrecht.
The investigators also grouped blood samples based on brain injury markers, and injected mice with IgGs obtained from these samples. The injections led to unique symptom patterns.
"This finding supports the idea that long COVID is not a single condition but a heterogeneous disease with different biological drivers analyses,” noted co-senior study author Jeroen den Dunnen, Ph.D., an Associate Professor at Amsterdam UMC.
Additional work indicated that there are higher than normal levels of autoantibodies in long COVID patients, which can target many human proteins, some of which are related to neuronal signaling, metabolism, and immune regulation. Some patients carried these autoantibodies for many years.
Since antibodies taken from patients with other disorders, like fibromyalgia, can also cause symptoms in animal models, there may be similar immune pathways involved.
More work will be needed, particularly because of the small number of samples analyzed in this study, but researchers are making headway in our understanding of long COVID, and may eventually be able to use this data to create therapeutics for this serious condition.
Sources: University Medical Center Utrecht, Cell Reports Medicine
