Trial Report Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid® in a Long COVID cohort: a case series, 2026, Pridgen et al

Chandelier

Chandelier

Senior Member (Voting Rights)
Preprint, see post #14 for peer-reviewed paper.
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Full title: Comparison of IMC-2 alone and IMC-2 and Paxlovid® shows substantial short and long-term efficacy in reducing symptoms of Long COVID with combination therapy: a case series

Comparison of IMC-2 alone and IMC-2 and Paxlovid® shows substantial short and long-term efficacy in reducing symptoms of Long COVID with combination therapy: a case series

IntroductionLong COVID (LC), an infection-associated chronic illness (IACI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may have uti...
www.researchsquare.com www.researchsquare.com

Authors: David Putrino, William Pridgen

Abstract​


Introduction​

Long COVID (LC), an infection-associated chronic illness (IACI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may have utility in treating patients with the illness.

Methods​

We studied a convenience sample of patients engaged in an extended course of a combination of antiviral medications, either IMC-2 Only (IO) or IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label, to people with LC being treated at an outpatient clinic. The Patient Global Impression of Change (PGIC) was used to measure response to the therapy over time, with a primary focus on fatigue symptom reporting and a secondary focus on brain fog and dysautonomia symptoms. In addition, visual analogue scales (VAS) were used to track perceived symptom improvements.

Results​

Twenty-seven people with LC were approached for treatment, of whom 24 completed one or both protocols. Twelve were treated with IO and twelve were given the continuous IP combination. A reduction in fatigue, reported on the PGIC, was observed in both groups, but those who received IP experienced a statistically significant improvement compared to those who received IO (p < 0.0001). Similarly, using a VAS, patients reported an average 55.3% (p < 0.0001) greater reduction of fatigue in the IP group, compared with the IO group. Patients who completed the IP intervention demonstrated significant durability in their clinical benefit, with reported symptom improvements remaining consistent at 120-, 305- and 731-day follow-ups.

Discussion​

This small, open-label case series provides pilot evidence to support the need for a larger trial of combination antivirals for people living with LC. Based on these results a larger, controlled trial of IMC-2 paired with Paxlovid should be conducted.

Conflict of interest​

WLP is a partner and founder at PridCor Therapeutics, a company that holds a patent containing components making up IMC-2.



Acknowledgements​

We are grateful to the Polybio Research Foundation and the Steven & Alexandra Cohen Foundation for supporting DP in manuscript preparation duties. We would also like to express our gratitude to the people with Long COVID who permitted their data to be shared for this publication.
 
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IMC-2 is a novel combination of Valacyclovir and Celecoxib that may have utility in addressing persistent or reactivating herpesviruses and may be relevant to the clinical care of people with Long COVID.

Pridgen has been pushing this stuff for a while.
 
Jaybee00 said:
Where is the paxlovid only treatment???

Probably didn’t want to show that you don’t need the IMC-2.
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Well, studies have already shown Pax not to work, so you purposefully don't have a only Pax group because otherwise you'd run into the problem of showing something works as well as something that doesn't work at all. But of course Putrino has already published a largely identical study for only Pax...
 
Jonathan Edwards said:
It seems that this was open label, which rather destroys any usefulness. Why on earth was it not blinded?
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Page by Putrino Lab | @putrinolab.bsky.social

Happy to share some new #LongCOVID data that went to pre-print today. Before we begin breaking this down, one caveat: this work MUST be validated by a well-powered placebo-controlled randomized controlled trial before we can get too excited, but this is www.researchsquare.com 1/
skywriter.blue

After listening to members of the community, we met Dr Skip Pridgen: a brilliant clinician who had been working with Long COVID patients utilizing combination antivirals. Prior to COVID, Dr Pridgen had been working with a drug formulation he called4/
"IMC-2": a combination of Valtrex and Celebrex that had antiviral activity, especially for alpha- and gamma-herpesviruses, in folks with complex chronic illnesses such as #fibromyalgia. Working on instinct, Dr Pridgen trialed this protocol in #LongCOVID and saw a little5/
improvement, but felt that more could be done. So, working on instinct, a 15-day pulse of Paxlovid was added and more impressive results arose. All patients in this case series consented to the use of off-label meds and for their data to be used in this case series. Based on 6/
individual patient choice, we had the makings of a natural experiment, where some patients decided they wanted to try IMC-2 alone, whilst others wanted to try IMC-2 + Paxlovid. So we were able to split the data we had access to into two groups.
Click to expand...
 
dave30th said:
it's a case series, not a trial.
Click to expand...

I think that is quite generous.
Chandelier said:
We studied a convenience sample of patients engaged in an extended course of a combination of antiviral medications, either IMC-2 Only (IO) or IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label, to people with LC being treated at an outpatient clinic.
Click to expand...

It seems it was a pseudo-trial. I have never heard of a convenience sample before. But it seems they were deliberately comparing two treatments (without any proper methodology). It is time people who claim to have a 'biomedical' interest in these conditions showed some attempt to do better than the BPS people in terms of methodology. Otherwise what's the point? Fluge and Mella have shown that it can be done.
 
Chandelier said:

Page by Putrino Lab | @putrinolab.bsky.social

Happy to share some new #LongCOVID data that went to pre-print today. Before we begin breaking this down, one caveat: this work MUST be validated by a well-powered placebo-controlled randomized controlled trial before we can get too excited, but this is www.researchsquare.com 1/
skywriter.blue
Click to expand...
I think I'll adopt that phrase: "working on instinct" when I feel the need.

Per the above report: (my bolding)

"....alpha-gamma-herpesviruses, in folks with complex chronic illnesses such as #fibromyalgia. Working on instinct, Dr Pridgen trialed this protocol in #LongCOVID and saw a little5/improvement, but felt that more could be done. So, working on instinct, a 15-day pulse of Paxlovid was added and more impressive results arose."
 
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Sharing in light of my above comment about celecoxib possibly being what is helping people (if these are real responses in this and the other celecoxib/antiviral trials)



If there ever actually is a sizeable controlled study the investigators have a moral duty to include a celecoxib alone arm. Otherwise they run the risk of mass unnecessary prescription of antivirals in the event the trial is successful.
 
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Merged posts
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Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid® in a Long COVID cohort: a case series

William L. Pridgen, David Putrino

Introduction: Long COVID (LC) is an infection-associated chronic condition and illness (IACCI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may be useful in treating patients with the illness.

Methods: A convenience sample of patients undergoing an extended course of antiviral therapy was studied. Patients received either 120 days of IMC-2 only (IO) or 120 days of IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label at an outpatient clinic for people with LC. The Patient Global Impression of Change (PGIC) was used to measure therapy response over time, with primary focus on fatigue and secondary focus on brain fog and dysautonomia. Visual analog scales (VAS) were also used to track perceived symptom improvements.

Results: A total of 27 people with LC were approached for treatment, of whom 24 completed one or both protocols. Twelve received the IO protocol, and 12 received the continuous IP combination. Both groups reported reductions in fatigue on the PGIC, but participants receiving IP experienced a statistically significant improvement compared with those receiving IO (p < 0.0001). Similarly, using a VAS, patients in the IP group reported an average 55.3% (p < 0.0001) greater reduction in fatigue than the IO group. Participants who completed the IP intervention demonstrated durable clinical benefit, with symptom improvements remaining consistent at 120-, 305-, and 731-day follow-ups.

Discussion: This small, open-label case series provides pilot evidence supporting the need for a larger trial of combination antivirals for people living with LC. Based on these results, a larger, controlled trial of IMC-2 paired with Paxlovid is recommended.

Frontiers | Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid® in a Long COVID cohort: a case series

IntroductionLong COVID (LC) is an infection-associated chronic condition and illness (IACCI) with no currently approved treatments. In order to address SARS-...
www.frontiersin.org www.frontiersin.org
 
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IMC-2, a novel combination of valacyclovir and celecoxib, may have utility in addressing persistent or reactivating herpesviruses and could be relevant to the clinical care of people with LC.
Click to expand...
 
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