BREAKING! U.S. NIH Study Shows That A Variety Of Neuropathic Symptoms May Manifest After COVID-19 Shots!

A surprising new study led by researchers from the National Institute of Neurological Disorders and Stroke- U.S. National Institutes of Health-Bethesda that also involved medical scientists from Thomas Jefferson University, Icahn School of Medicine at Mt Sinai, Johns Hopkins University School of Medicine, Massachusetts General Hospital and Harvard University has found that a variety of neuropathic symptoms may manifest after COVID-19 shots and in some patients, it  might be due to an immune-mediated process.


 
To date it has been reported that various peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation.
 
However, it has not been explored if similar manifestations can occur with the vaccination remains unknown.
 
In an observational study, the research team studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination.
 
Almost 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01-10%) and 19% showed abnormal axonal swelling.
 
Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17).
 
In all, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5-9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks.
 
The study findings from this observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2022.05.16.22274439v1
 
The study team noted that vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) essentially reduce morbidity and mortality and are crucial tools to contain the COVID-19 pandemic. FDA-approved vaccines are associated with a relatively small number of post-immunization adverse effects.
 
Thailand Medical News notes that currently in the United States (US), reports to the Vaccine Adverse Event Reporting System (VAERS) consist of various systemic and neurologic manifestations. It was reported that these adverse events are observed after mass vaccination programs and might have similar immunologic mechanisms wit h post-infection neurologic complications. Although rare, immune-mediated neurologic complications are less severe than after infection.
 
The study team in the current observational study clinically evaluated patients with new-onset paresthesia regardless of autonomic symptoms incident to COVID-19 vaccination. From January to September 2021, 23 patients were assessed for new onset of polyneuropathic symptoms within a month of SARS-CoV-2 vaccination. Medical records of the patients were abstracted to collect data. Excluded persons were those with recurrent neurologic symptoms or having non-neurologic complications and those at risk of developing dysautonomia and neuropathy.
 
All participants with autonomic symptoms were subjected to standard autonomic nervous system (ANS) testing.
 
Variability in heart rate after six to eight slow deep breaths per respiratory cycle was assessed. Tilt table tests were performed for 10 minutes following 20 minutes of supine rest. Postural orthostatic tachycardia syndrome (POTS) was defined as the sustained increase of 30 beats per minute or higher from the baseline after 10 minutes in the upright position without orthostatic hypotension.
 
Also, two skin biopsies were removed from the lower leg to evaluate small fiber neuropathy (SFN).
 
In the study, the median age of the 23 subjects was 40 years, and a majority were women (21). None of the patients had prior neurologic illnesses. Five patients reported tachycardia, skin-flushing, and elevated blood pressure after administration of the COVID-19 vaccine, which lasted for 30 minutes or less and resolved entirely.
 
Interestingly, all patients showed neurologic symptoms in at least 21 days following COVID-19 vaccination. Subjects were vaccinated with Pfizer’s BNT162b2, Moderna’s mRNA-1273, AstraZeneca’s ChAdOx1, or Janssen’s JNJ-78436735 vaccine. Fourteen patients showed neurologic symptoms after the first dose, while nine developed after receiving the second.
 
All the research participants complained of moderate to severe paresthesia and burning sensation in upper or lower limbs. About 60% of the participants developed autonomic symptoms, including new-onset Raynaud’s phenomenon, episodic tachycardia, and heat intolerance. Of the 12 patients undergoing ANS testing, abnormal findings were observed for 11 of them and six fulfilled the criteria for POTS. Seven subjects had diminished length-dependent sweat production, a characteristic feature of SFN. Magnetic resonance imaging (MRI) of the brain or spine available for 16 patients revealed no significant abnormalities.
 
Importantly, of the 16 participants who underwent skin biopsies, five patients showed subthreshold nerve fiber density, two with borderline density at the distal side of the leg, and three showed axonal swellings in the fibers, all of these exhibited nerve conduction velocities which confirmed small-fiber axonal neuropathy.
 
Also, C4d complement deposition on endothelial cells was observed in five patients compared to nine age-matched controls.
 
In the study, twelve patients were treated with oral corticosteroids; seven received a standard prednisone dose for a week with a subsequent taper of 20% of the initial dose showed significant improvement in neurologic symptoms after two weeks.
 
However, three patients showed persistent symptoms of dysautonomia and SFN for five to nine months and were managed on intravenous immunoglobulin (IVIg) treatment. IVIg treatment was significant as symptoms improved in two weeks, resolving entirely for one of them and remaining as mildly residual in the other two. Among the non-recipients of immune therapies, partial recovery was evident in seven patients, complete in just one participant (by 12 weeks post-onset of symptoms), and three had no improvement.
 
The study team observed that all patients experienced neuropathic symptoms within three weeks of vaccination.
 
However, referral bias limits the findings given the study’s observational nature, and the lack of a control group precludes attributing a causative role despite the temporal association of vaccines to symptoms.
 
Significantly, oligoclonal bands in two of the five tested patients’ cerebrospinal fluid, deposition of immune complexes (C4d), and response to immunotherapy suggest a possible immune association.
 
Despite some patients responding positively to corticosteroids or IVIg treatment, their use should be cautiously monitored or viewed in the context of clinical trials.
 
The study team says that further research is necessary, however, to determine whether the SARS-CoV-2 vaccines causes neuropathies. 
 
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