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3CL Protease Inhibitors IN Chronic Long Covid
A Case Review:
Effects of 3CL Protease Inhibitors Paxlovid® and Tollovid™ in a Patient with Chronic
Long Covid
Andrew A. Blumenthal
Lee A. Morgentaler
Author Note
Andrew A. Blumenthal https://orcid.org/0000-0001-9504-4898
Conflict Statement: Andrew Blumenthal is employed by Todos Medical, USA
Correspondence concerning this article should be addressed to Andrew Blumenthal, c/o Todos
Medical, Ltd, 40 Wall St, Suite 2702, New York, NY 10005
Email: Andrew.b@todosmedical.com
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3CL Protease Inhibitors IN Chronic Long Covid
Abstract:
The SARS-COV2 virus continues to impact over 550 million individuals globally and
over 80 million Americans nationally. COVID-19 and Acute Sequelae of SARS-CoV-2 (PASC),
or Long COVID, are major public health problems. Emerging evidence suggests the PASC, for
many, may in fact be due to persistent SARS-CoV-2 infection that is able to evade vaccine or
infection-induced immunity and cause recurring and persistent symptoms. PASC does not appear
to protect against new acute SARS-CoV-2 infection, and PASC may in fact contribute to poor
outcomes in new acute infections and/or recurrent symptoms from prior infection. We report a
case of a patient with SARS-CoV-2 infection and persistent Long Covid symptoms for over 2
years, who received the therapeutic intervention Paxlovid®. After finding no relief using
Paxlovid®, the subject initiated supplementation with the 3CL protease inhibitor immune
support dietary supplement Tollovid™. Within 30 days of using Tollovid™, the subject’s
neutralizing antibodies levels increased by 30% and the subject reported being at 80% of her pre-
COVID baseline health.
Key Words: Tollovid, Paxlovid, long haul, PASC, COVID, cpas, nabs, 3cl, protease
inhibition, neutralizing antibodies, persistent.
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3CL Protease Inhibitors IN Chronic Long Covid
Case Report:
A 40-year-old, 5’ 7”, 150-pound, female was in in good health with hopes to compete in
a bodybuilding competition becomes bedridden post COVID-19 infection. The subject has no
underlying medical conditions and no relevant family history of medical conditions. On March
11, 2020, the subject tested positive for COVID-19 via nasopharyngeal PCR test. The subject’s
initial symptoms were gastrointestinal bloating, diarrhea, fever, sore throat, shortness of breath,
and significant fatigue. Despite testing negative after 14 days of self-quarantine, the subject’s
symptoms persisted with the exception of the GI disturbance. One month after the initial
infection, the subject experienced a loss of olfactory and gustatory senses and shortness of breath
that required her to utilize a CPAP device.
In June 2020, while the subject’s flu-like symptoms and sore throat resolved, she
developed new onset of symptoms including numbness and tingling sensations to the left side of
her body, loss of taste and smell, exacerbation of anxiety symptoms, heat intolerance, nausea,
and shortness of breath with PCO2 level excursions to 92%. The subject was diagnosed with
small fiber neuropathy. Her symptoms remitted and relapsed over a period of months with
deterioration to being primarily bedbound. Subject was later diagnosed with post-exertional
fatigue and dysautonomia, describing herself as feeling “poisoned and electrocuted at the same
time.” In August 2020 the subject received peptide treatments for 2 months and reported
improvement to 60% of her pre-COVID baseline health. In December 2020, a cardiologist
diagnosed the subject with first-degree heart block and supraventricular tachycardia. Over the
next 12 months, the subject sought assistance from 18 medical providers and was diagnosed with
POTS by her neurologist.
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3CL Protease Inhibitors IN Chronic Long Covid
On April 11, 2021, the subject received her first Pfizer-BioNTech SARS-CoV-2 vaccine,
which was followed by the swift return of prior symptoms. The subject was housebound until the
symptoms abated 17 days later. On May 14, 2021, the subject received her second Pfizer-
BioNTech SARS-CoV-2 vaccine. She noted a rapid onset of symptoms including twitching of
the eyes and lips, tinnitus, and brain fog.
The subject resumed peptide treatment in August 2021 but was discontinued after 90
days due to financial considerations. In January 2022, the subject experienced Post Exertional
Malaise (PEM) so severe as to require the use of a wheelchair for 90 days. In April of 2022,
laboratory testing was positive for Epstein Barr Virus, Bartonella, Herpes-6, and roundworm. On
May 12, 2022, the patient started a 5-day regimen of Paxlovid® with no noticeable positive
effect and experienced nausea and a metallic taste in her mouth.
On May 18, 2022, the subject started a regimen of Tollovid™, a known 3CL protease
inhibitor immune support dietary supplement (Todos Medical, 2021). Within 10 days of
initiation, the subject describes being at 55% of her premorbid condition with decreased gastric
discomfort, return of regular bowel function, and increased energy allowing her to return to work
1 day per week.
Tollovid™ supplementation was discontinued at the 10-day mark. Within 3 days of
cessation, there was a gradual return of prior symptoms. On June 2, 2022, the subject initiated a
30-day course of 12 capsules per day of Tollovid Max™ by mouth with a titration down to 8
capsules per day beginning July 1, 2022 and continuing through July 15, 2022 (Ltd, 2022).
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3CL Protease Inhibitors IN Chronic Long Covid
Two weeks later, she noted persisting neuropathy, muscle pain, and fatigue symptoms.
Gastric discomfort and energy levels improved. On July 18, 2022, she reported being at 80% of
her pre-COVID baseline health, a 30% improvement prior to Tollovid™ use. The subject stated,
“I now feel better than I have in the past 27 months.”
Blood samples collected on June 2, 2022, and assayed using the cPass neutralizing
antibody test (surrogate viral neutralization test) demonstrated a 59.2% (1,313 U/ml) inhibition
of SARS-CoV-2 cellular entry suggesting her antibody response was insufficient to neutralize
the viral load (CPass SARS-CoV-2 Neutralization Antibody Detection Kit Instructions for Use,
n.d.).
Subsequent cPass nAb testing collected on July 7, 2022, indicated neutralizing antibody
inhibition increased to 89% (>6,000 U/ml) a 30% increase from the previous measurement. This
increase in neutralizing antibody levels is the likely result of immune response to active infection
and is compelling evidence of viral persistence. The subject is expected to continue taking
Tollovid™ at the therapeutic dosage.
Discussion:
This case study is evidence of the potential role of viral persistence in Long COVID. The
subject had a positive response to extended use of 3CL protease inhibitors resulting in a
reduction of symptoms. Effective symptom management is reported with continued
supplementation with the 3CL protease inhibitor Tollovid™ at the last known effective dose.
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3CL Protease Inhibitors IN Chronic Long Covid
References
cPass SARS-CoV-2 Neutralization Antibody Detection Kit Instructions for use. (n.d.).
https://www.fda.gov/media/143583/download
Ltd, T. M. (2022, May 2). Todos Medical Receives New FDA Certificate of Free Sale for
Tollovid® Max Strength Including 5 Day Dosing, 30 Day Dosing and 3CL Protease
(3CLpro, Mpro, Nsp5) Inhibitor Claim. GlobeNewswire News Room.
https://www.globenewswire.com/news-release/2022/05/02/2433697/0/en/Todos-Medical-
Receives-New-FDA-Certificate-of-Free-Sale-for-Tollovid-Max-Strength-Including-5-
Day-Dosing-30-Day-Dosing-and-3CL-Protease-3CLpro-Mpro-Nsp5-Inhibitor-
Claim.html
Todos medical receives new FDA certificate of free sale for Tollovid Daily including 3CL
protease inhibitor claim. (2021, July 22). Todos Medical
Ltd. https://investor.todosmedical.com/news-events/press-releases/detail/118/todos-
medical-receives-new-fda-certificate-of-free-sale-for