Although researchers have repeatedly looked for any signs of whole viral genome in long COVID, none has been found. Only mRNA, fragmented RNA, DNA, and spike protein, all of which are foreign to our immune system, have remained. Numerous studies have found lingering spike protein and/or mRNA in various tissues, including:
A recent study showed that viral RNA can persists for years. Researchers specifically identified cellular SARS-CoV-2 RNA in the gut tissue of all participants with long COVID symptoms who underwent biopsy in the absence of reinfection, ranging from 158 to 676 days following initial COVID-19 illness. Using a novel radiopharmaceutical agent that detects specific molecules associated with a type of white blood cell called T lymphocytes, researchers found uptake of the tracer was significantly higher in post-acute COVID-19 participants compared to pre-pandemic controls in the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. The researchers add, “As long COVID is increasingly being framed as having potential neurological underpinnings, it is possible that spinal cord and brainstem tracer uptake observed in this study may represent T cell trafficking to CNS tissues with residual viral components”. Note: all but one of the patients were vaccinated. These autoreactive T cells being fueled by lingering viral fragments/spike protein are a key driver of autoimmune and neurodegenerative disease.
 Image Credit: SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19. https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1 The mRNA vaccines instruct the body to produce spike proteins: But for how long? No one really knows the long-term implications of lingering mRNA post virus or post vaccine. Since the mRNA vaccines were designed substituting methyl-pseudouridine for all the uridine nucleotides to stabilize RNA against degradation, could lingering modified mRNA post vaccine be even more difficult for the body to break down? Theoretically, the lipid nanoparticles (LNPs) in which the mRNA is encapsulated should have a very restricted biodistribution, targeting the draining axillary lymph nodes. However, a pharmacokinetic study performed by Pfizer for the Japanese regulatory agency shows that the LNPs display an off-target distribution on rodents, accumulating most in organs such as the spleen, liver, pituitary gland, thyroid, ovaries and in other tissues. Therefore, it is important to note this widespread distribution via LNP’s to essentially every cell is translating in spike protein production. Spike protein is a very harmful toxin and is responsible for most of the pathology for both the infection and the vaccines. Multiple organs, cells, blood vessels, and even the brain can be harmed.  Striking Similarities and Molecular Mimicry. The spike protein of SARS-CoV-2 has extensive sequence homology with multiple endogenous human proteins and could prime the immune system toward development of both auto-inflammatory and autoimmune disease. Because of molecular mimicry with the spike protein, a diverse spectrum of autoantibodies has been reported. These autoantibodies are the likely cause of Guillain-Barré Syndrome (GBS), transverse myelitis, immune thrombocytopenia, Small Fiber Neuropathy (SFN)/Autonomic neuropathy and many more autoimmune diseases either new onset or flares. Peripheral nerves in the line of fire.  It is estimated that 59% of COVID-19 patients show signs of neuropathy in the mid- or long-term. Over 70% of the vaccine injuries related to the COVID vaccines have neuropathy symptoms.  To study further how and why COVID-related peripheral neuropathies occur including small-fiber neuropathy, multifocal demyelinating neuropathy, and axonal neuropathy, this recent work showed sensory nerves to be quite vulnerable post infection but not due to lingering virus; rather, infected neurons released spike protein, nucleocapsid proteins, and other viral fragments. Sensory neurons exposed to SARS-CoV-2 replicate SARS-CoV-2 RNA and produce viral proteins but do not shed the virus, only viral fragments.  Small Fiber Neuropathy. SFN is a disorder in which only the small sensory cutaneous nerves are affected. Most patients experience symptoms that may include unusual sensations such as pins-and-needles, pricks, tingling and numbness; some may also experience burning pain or coldness and electric shock-like, brief painful sensations. Although diabetes and vitamin B12 deficiency are common causes of SFN, no cause is found in around 50% of the cases known as idiopathic SNF. One recent study examined the incidence of small fiber neuropathy (SFN) post vaccine and post infection. One proposed mechanism of post-vaccine neuropathy is through molecular mimicry. Lingering spike protein can create autoantibodies post virus and post vaccine and may trigger identical immuno-inflammatory cascades resulting in symptoms. For more information about complications arising post vaccine and post COVID, see: https://www.suzannegazdamd.com/blog---long-covid/the-dramatic-rise-in-autoimmune-disease-post-covid-and-post-vaccine Also, see the full long COVID series at: https://www.suzannegazdamd.com/blog---long-covid Once again, we know that spike protein is a very harmful neurotoxin. With post-COVID infection or post-COVID vaccine, the cause of SFN is predominately autoimmune driven. It requires a small fiber nerve biopsy to diagnose SFN. However, a normal SFN biopsy does not rule out SFN; as shown in this study, only 39% of patients with suspected SFN had positive results. Circulation to Peripheral Nerves is Impaired. I suspect as well that many of the SFNs we are seeing now post COVID or post vaccine are also being driven by endothelial damage provoked by lingering spike protein. Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues.
Spike protein binds to the ACE 2 receptors on the endothelial lining of all large and small blood vessels, as it activates platelets and other clotting factors. The microclots formed contain amyloid making them very resistant for the body to breakdown. These microclots can particularly affect the microcirculation, thereby compromising the blood supply to these small nerve fibers. We have seen this before with SFN related to diabetes. SFN may also be secondary to vasculitis. Vasculitis is an autoimmune disease that causes inflammation and narrowing of blood vessels (arteries, veins, and capillaries). There have been multiple case reports of new onset vasculitis post vaccine.  In this next study, dermal vasculitic lesions in COVID-19 were caused by SARS-CoV-2 spike protein deposition (note that no virus was found), followed by endothelial damage. In this photo taken from this study, look at all the blue in the dermal cells. This is a massive amount of spike protein; it’s important to point out as well that visual endothelial changes were found in 60% of the 25 study subjects’ skin samples.  H&E stained skin punch biopsy from patient’s back. Scale bar 50 μm. Small fiber neuropathy can manifest with a wide range of symptoms. While SFN is often associated with cutaneous sensory signs (numbness and tingling). Symptoms can be very diverse, especially when autonomic nerve fibers are impaired. Symptoms of dysautonomia can include temperature dysregulation, variability in heart rate, and blood pressure, POTS, dry eyes and dry mouth, swelling or color and temperature changes in the extremities, vascular changes, gastrointestinal issues, bladder problems, sexual dysfunction, and even visual difficulties. One online survey by the KFF, formerly known as the Kaiser Family Foundation, of over 2,300 adults with long COVID found that 67 percent had moderate to severe autonomic nervous system dysfunction. This was unrelated to the severity of their initial COVID-19 illness. Multiple autoantibodies are identified in both COVID-related autonomic disorders and non-COVID autonomic disorders, implying a possible underlying autoimmune pathology. The prevalence and concentrations of evaluated autoantibodies to vasoregulatory and autonomic nervous system receptors were significantly higher in long COVID and correlates with intensity of cognitive and physical impairment.  Additionally, complex syndromes of chronic pain, fatigue and cognitive impairment can be linked to autoimmune dysautonomia and SFN. Pain with SFN can be very atypical as well, featuring musculoskeletal pain, muscle cramps, fasciculations, and widespread unexplained aches.  The cumulative toxic effect on neurological tissue from chronic exposure to spike protein elicited by persistent expression of spike and or repeated periodic injections is not known. The expression “canary in the coal mine” refers to something which warns of the coming of greater danger or trouble by a deterioration in its health or welfare. And it seems especially relevant now to help us to remember to pay close attention to any rise in potential neurological disease. I encourage you to stay curious. Times have changed and perhaps more than ever, we desperately need stronger clinical acumen to help all our patients.
In hope and healing, Dr. Suzanne Gazda References: Schwartz B, Moudgil S, Pollina F, et al. (August 16, 2023) Small Fiber Neuropathy After SARS-CoV-2 Infection and Vaccination: A Case-Based Comparison. Cureus 15(8): e43600. doi:10.7759/cureus.43600. https://www.cureus.com/articles/162991-small-fiber-neuropathy-after-sars-cov-2-infection-and-vaccination-a-case-based-comparison?utm_medium=email&utm_source=transaction#!/ Akihoko, A. et al. Small Fibre Neuropathy Is Associated With Impaired Vascular Endothelial Function in Patients With Type 2 Diabetes. Front Endocrinol. (2021). https://www.frontiersin.org/articles/10.3389/fendo.2021.653277/full Gawaz, A. et al. SARS-CoV-2 induced vasculitic skin lesions are associated with massive spike protein depositions in autophagosomes. Journal of Investigative Dermatology. (2023). https://www.jidonline.org/article/S0022-202X(23)02501-0/fulltext SARS-CoV-2 mRNA Vaccine (BNT162, PF-0 7302048): 2.6.5.5B. 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