COVID-19 Infection and Vaccination Causes Small Fiber Neuropathy!

Medical News: The COVID-19 pandemic has not only challenged healthcare systems but also raised many questions about its long-term effects on patients. Among the lesser-known impacts is small fiber neuropathy (SFN), a condition affecting the small nerves responsible for sensations like pain and temperature and often linked to autonomic nervous system dysfunction. Italian researchers from the IRCCS Institute of Neurological Sciences in Bologna and the University of Genova recently conducted a study to explore this link, examining patients who developed SFN following either a natural COVID-19 infection or an mRNA COVID-19 vaccination.


COVID-19 Infection and Vaccination Causes Small Fiber Neuropathy!

This Medical News report will dive into their findings, which suggest that both infection and vaccination may be associated with SFN, although the frequency and severity appear more significant in patients with previous COVID-19 infections.
 
What is Small Fiber Neuropathy?
SFN is a type of peripheral neuropathy that affects small nerve fibers, often leading to symptoms like burning pain, tingling, or numbness, primarily in the hands and feet. In some cases, SFN can also impair the autonomic nervous system, which controls bodily functions like sweating, heart rate, and digestion. For people experiencing SFN post-COVID-19, symptoms usually emerge within a few months following infection or vaccination, and they may linger as part of what is sometimes called “long COVID.”
 
Study Overview
The research team recruited 66 patients for this case-control study, dividing them into three groups. The first group consisted of 33 individuals who developed sensory and autonomic symptoms after a natural COVID-19 infection, referred to as "P-COVID." The second group included 33 individuals who experienced similar symptoms after receiving an mRNA COVID-19 vaccine, termed "P-VAC." A control group of 33 healthy individuals was also included for comparison. Patients in the control group had no COVID-19 history and were selected before the pandemic.
 
Key Findings: The Impact of Infection and Vaccination on Small Nerve Fibers
The study results highlighted a notable decrease in somatic small nerve fibers in both P-COVID and P-VAC patients compared to healthy controls. However, while both groups had similar rates of somatic small fiber damage, the P-COVID group showed a higher incidence of SFN. An astounding 94% of P-COVID patients exhibited SFN, compared to 79% in the P-VAC group.
 
The researchers performed skin biopsies to evaluate nerve density in different skin areas. Their analysis showed that small fiber density was lower in both groups compared to healthy individuals, indicating nerve damage. Autonomic innervation (nerves controlling functions like sweating and blood flow) appeared unaffected in skin biopsies, suggesting that the damage was mostly to the sensory small nerve fibers.
 
Autoimmune Dysfunction and Sma ll Fiber Neuropathy
Interestingly, while the study found autoimmune abnormalities common in both P-COVID and P-VAC patients, these were not linked to SFN. This means that even though autoimmune conditions like Hashimoto’s thyroiditis were prevalent, they didn’t seem to contribute directly to SFN. Rather, the researchers suggested that the immune response triggered by the COVID-19 virus or vaccine might be at play.

In fact, about 58% of P-VAC and 55% of P-COVID patients exhibited autoimmune dysfunctions. Some showed elevated antinuclear antibodies (ANA) levels, while others had antibodies against specific antigens like GM1 and GD1d. However, autoimmune conditions did not differ significantly between the groups.
 
Symptom Severity: COVID-19 Infection vs. Vaccination
P-COVID patients not only had a higher rate of SFN but also scored higher on a symptom scale for autonomic dysfunction, known as the COMPASS-31 scale. These scores suggest subtle autonomic impairment, even though skin biopsies did not show clear damage to autonomic nerves.
 
A distinguishing feature was the timing and nature of symptom onset. Most P-VAC patients experienced symptoms shortly after their first dose, while some developed symptoms after the second or third dose. In P-COVID patients, symptoms usually took longer to appear, reflecting a different disease course. For many, symptoms persisted beyond three months, meeting criteria for what is sometimes called "long COVID."
 
Possible Mechanisms: How Might COVID-19 and Vaccination Lead to SFN?
The exact mechanism by which COVID-19 infection or vaccination might cause SFN remains unclear, but researchers propose several possible explanations. Immune activation and inflammation appear to be the leading suspects. COVID-19, in particular, is associated with a “cytokine storm,” an overreaction of the immune system that releases inflammatory substances that might harm nerve cells. Cytokines, molecules involved in inflammation, can bind to nerve receptors and cause a heightened pain response.
 
Another theory is direct viral invasion. SARS-CoV-2 may affect neurons through proteins like neuropilin-1 and ACE2, which the virus uses to enter cells. Though studies have shown that these proteins are present in neurons, no autopsies have definitively found the virus in brain or peripheral nerves. This theory remains speculative but is worth exploring further.
 
Vaccines, especially mRNA vaccines, work by inducing an immune response against the virus's spike protein. Some believe that the immune response generated by these vaccines could also inadvertently activate pain-sensitive neurons or cause low-level inflammation, contributing to symptoms of SFN.
 
Limitations and Future Research Directions
While this study sheds light on the connection between COVID-19, vaccination, and SFN, it has limitations. The study did not include a control group of vaccinated individuals who did not report symptoms, which would have helped determine whether SFN could be present without any associated symptoms. Future studies might include inflammatory markers in skin biopsies to understand better whether inflammation drives SFN in COVID-19 patients.
 
Conclusion
This research is essential for understanding the complexities of post-COVID-19 and post-vaccine health issues, particularly for conditions like SFN that affect daily life. Although both COVID-19 infection and vaccination can be associated with small nerve damage, the higher incidence and severity in P-COVID patients suggest that natural infection may pose a greater risk for developing SFN than vaccination. Researchers also observed that this type of neuropathy primarily affected sensory fibers, leaving autonomic fibers largely intact, though P-COVID patients showed subtle signs of autonomic dysfunction.
 
Given the prevalence of autoimmune abnormalities in these patients, the findings suggest that immune activation, rather than direct viral infection or existing autoimmune diseases, may be a more likely cause of SFN in both post-COVID-19 and post-vaccine conditions. While SFN’s impact on life quality can be profound, this study offers hope by helping clarify the cause, which could inform better management and treatment strategies for those affected.
 
The study findings were published in the peer-reviewed European Journal of Neurology.
https://onlinelibrary.wiley.com/doi/10.1111/ene.16538
 
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https://www.thailandmedical.news/news/harvard-study-shows-that-those-with-prolonged-long-covid-will-likely-suffer-from-nerve-damage-and-peripheral-neuropathy
 
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