Alarming Changes in Transitional B Cells Reveal Hidden Immune Dysregulation in Long COVID Sufferers

Medical News: Russian Scientists Uncover Major Immune Abnormalities in Long COVID Patients by Tracking Key B Cell Subtypes
A new breakthrough study by Russian researchers has shed light on the mysterious immune mechanisms that may be driving long COVID, a debilitating condition affecting millions worldwide. The team found that patients suffering from long COVID have a distinct imbalance in their B cell populations, particularly a dramatic decrease in a specialized group called transitional B cells.


Alarming Changes in Transitional B Cells Reveal Hidden Immune Dysregulation in Long COVID Sufferers

Conducted by scientists from the Laboratory of Molecular Immunology at the Saint Petersburg Pasteur Institute, the Department of Immunology at the First Pavlov State Medical University of Saint Petersburg, and the North-Western District Scientific and Clinical Center named after L.G. Sokolov, this new study explored subtle but powerful shifts in the body’s immune system following SARS-CoV-2 infection. This Medical News report delves into how these discoveries may offer crucial answers to why some people never fully recover from COVID-19.
 
Long COVID and the Puzzle of Persistent Symptoms
Long COVID, officially defined by the World Health Organization, refers to the persistence of symptoms like fatigue, brain fog, shortness of breath, and cardiovascular issues for at least 12 weeks after an acute SARS-CoV-2 infection. The new research involved 63 individuals diagnosed with long COVID and compared them to 47 healthy people who previously had COVID-19 but made a full recovery.
 
Participants with long COVID reported a variety of lingering issues including hair loss (57%), appetite loss (52%), stomach discomfort (46%), and fluctuating blood pressure (100%). A significant number also suffered from fatigue, breathing difficulties, and psychological symptoms like anxiety and depression.
 
No Difference in Antibodies but Major Differences in Immune Cell Types
Interestingly, the study showed that the levels of IgG antibodies targeting SARS-CoV-2 were not significantly different between the long COVID group and the healthy group. This indicates that a person’s antibody response alone cannot explain the long-lasting symptoms.
 
The real discovery lay in the analysis of B cell subpopulations - a crucial group of immune cells responsible for producing antibodies. While the total number of B cells (CD45+CD19+) was similar in both groups, long COVID patients showed notable shifts in specific B cell types. They had an increased percentage of naive mature B cells (CD27 - CD38+), which are usually responsible for responding to new infections. However, their transitional B cells (CD27 - CD38+++) and double-negative B cells (CD27 - CD38−) - both of which play critical roles in immune regulation - were significantly lower than in healthy individuals.
 
Transitional B Cells and Autoimmunity Risk
Transitional B cells are immature B cells that re cently emerged from the bone marrow and are known to have regulatory functions. Their primary role is to ensure self-tolerance, helping the immune system distinguish between the body’s own cells and foreign invaders. A lack of these cells could lead to increased autoimmune activity - where the immune system begins to attack the body itself.

This discovery is deeply concerning, as it suggests that individuals with long COVID may be at greater risk of developing autoimmune complications. Similar reductions in transitional B cells have been observed in diseases like multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.
 
Cytokine Chaos Points to Inflammatory Imbalance
To further understand immune dysfunction in long COVID, the research team analyzed cytokines - chemical messengers released by immune cells. Out of 17 cytokines tested, three were notably elevated in long COVID patients: IL-5, IL-8, and IL-13.
 
Both IL-5 and IL-13 are associated with a branch of the immune response known as Th2 immunity, which plays a role in allergic reactions and antibody production. An increase in these cytokines may reflect heightened inflammatory signaling and contribute to the chronic symptoms seen in long COVID.
 
IL-4, another key Th2 cytokine, showed no significant difference between groups, adding complexity to the picture. IL-17 and MCP-1, other inflammation-related cytokines, were also elevated, hinting at widespread immune activation and possible tissue damage.
 
A New Predictive Marker for Long COVID Identified
One of the most compelling findings from this study came from an advanced statistical analysis known as QUEST classification. This method revealed that the percentage of transitional B cells could be used as a powerful predictor of long COVID. A cutoff value of less than 5.94% transitional cells was enough to classify individuals as long COVID patients with 95% sensitivity and 72% specificity.

This means that a simple blood test measuring transitional B cells could one day help diagnose long COVID or predict who might be at higher risk of developing it.
 
What Do These Findings Mean
The implications of this study are profound. The discovery that transitional B cells are drastically reduced in long COVID patients - paired with increased naive B cells and inflammatory cytokines - points to a deeper and potentially autoimmune-like process occurring in these individuals.
 
This aligns with emerging theories that suggest long COVID may have features in common with autoimmune diseases, where the body’s immune system mistakenly targets its own tissues. While the presence of antibodies alone does not differ between long COVID patients and those who recovered, the immune system's internal regulatory mechanisms appear broken in long COVID.
 
These findings also highlight why some patients suffer cognitive dysfunction, chronic fatigue, and even organ damage months after the initial infection has passed. Transitional B cells not only help regulate the immune system but are also involved in preventing harmful inflammation, particularly in delicate tissues like the brain and lungs.
 
By identifying transitional B cell depletion as a central feature of long COVID, the study lays the groundwork for new diagnostic tools and perhaps even future treatments aimed at restoring immune balance.
 
A Multidisciplinary Future for Long COVID Treatment
Despite the focus on immunological dysfunction, the authors stress that long COVID is not solely an immune disorder. Its development is also shaped by a person’s experience during the acute phase of COVID-19, vaccination status, mental health, and even socioeconomic conditions. For instance, vaccinated individuals are less likely to develop severe long COVID, and those with prior psychological stressors may face worse outcomes.
 
Therefore, treating long COVID will require a multidisciplinary approach that combines immunology, neurology, psychology, and public health to develop comprehensive care strategies.
 
Conclusion
This important study from a team of Russian scientists brings much-needed clarity to the immunological underpinnings of long COVID. While total B cell counts may appear normal, deeper analysis reveals a concerning loss of transitional B cells in affected individuals - cells that play a critical role in immune tolerance and regulation. Their depletion could open the door to autoimmune processes, explaining many of the persistent symptoms in long COVID patients.
 
Additionally, elevated Th2 cytokines such as IL-5 and IL-13 support the theory that long COVID is marked by chronic inflammation and immune misfiring. The ability of transitional B cell levels to predict long COVID with high accuracy is especially promising and could lead to better diagnostic tools. As our understanding grows, so too does the hope for targeted treatments that restore immune balance and improve quality of life for millions suffering from long COVID. But more research is urgently needed to validate these findings and explore therapeutic options to correct these immune abnormalities. In the future, immune profiling may become a standard tool to assess post-COVID risks and guide personalized care.
 
The study findings were published in the peer reviewed journal: Current Issues in Molecular Biology.
https://www.mdpi.com/1467-3045/47/4/245
 
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