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 researchsquare.com 1/
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an exciting first step and something that we hope will deepen our understanding of use of combination antivirals in the #LongCOVID community. A bit of background about how we got here: in early 2025 our team was part of a consortium that published a roadmap for targeting viral 2/ reservoir in pwLC. In this statement piece, we spoke about the need to be trialing not just monotherapies, but multi-drug combinations and for longer periods of time than just a few weeks. After publishing this work, we started to seek out docs that thelancet.com 3/
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might be doing this already. 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 called 4/ "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 little 5/ 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. Despite the length of the 7/
protocol (120 days), no one in the dataset dropped out, so we could do a fair comparison of outcomes. Also, Dr Pridgen was rigorous and fastidious in following these patients up for >600 days after the end of the protocol. Because this was not a formal clinical trial, Dr 8/ Pridgen did not use a whole lot of formal instruments to study symptom severity. However, he did capture the Patient Global Impression of Change (a well-validated metric for studying patient perception of improvement and has been used widely for chronic conditions like pain). 9/ The PGIC asks patients to rate their improvement on a scale of 1 to 7. Dr Pridgen captured these data on 3 prominent symptoms of patients attending his clinic: fatigue, brain fog (although we don't love this term, this is the language that was used at the time) and 10/
dysautonomia, and studied the 2 groups across different timepoints: Day 120, Day 305 and Day 731. When we analyzed the data a few interesting things popped out at us. First, IMC-2 + Paxlovid outperforms IMC-2 alone in improving fatigue, dysautonomia and brain fog (p<0.0001). 11/
Second, the effects in the IMC-2 + Pax group were highly durable, beyond 600 days post-treatment. This was encouraging that we weren't necessarily looking at a placebo effect or an antiviral protocol that had to be continued in perpetuity. Also of note: these patients were 12/
not "cured", just vastly improved. So we aren't looking at a silver bullet here, but we are potentially looking at something that can significantly improve someone's baseline. HOW TO THINK ABOUT THESE DATA: - This IS NOT a silver bullet and these data do not replace the need 13/ for a good quality placebo-controlled RCT. - This IS incredibly interesting pilot data that absolutely justifies the need for a rapid large-scale RCT to be performed. - As we turn eyes toward RECOVER-TLC next week, these are the sorts of interventions that we should be 14/ thinking about for the next iteration of clinical trial - novel, long-duration (because persistent pathogens won't be taken out easily), multi-drug (to address the complexity of LC pathobiology) and with early promising signals of efficacy. Finally, none of this would have 15/ possible without the hard work of Dr Pridgen and his team, willing to think outside the box and his amazing patients who have been so willing to speak with our team and recount their experiences. We have a long way to go on validating and developing this protocol, but this 16/ pre-print is an exciting first step in building an evidence-base for combination antiviral approaches to managing #LongCOVID. 🙏 /end