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

**Authors:** William L. Pridgen, David Putrino

PMC · DOI: 10.3389/fimmu.2025.1698271 · Frontiers in Immunology · 2026-01-05

## TL;DR

A case series found that combining IMC-2 with Paxlovid improved fatigue and other symptoms in Long COVID patients more effectively than IMC-2 alone.

## Contribution

This study provides early evidence that a combination of IMC-2 and Paxlovid may offer better outcomes for Long COVID patients compared to IMC-2 alone.

## Key findings

- Patients receiving IMC-2 and Paxlovid showed significantly greater fatigue reduction than those on IMC-2 alone.
- Symptom improvements in the combination group were durable, persisting at 120-, 305-, and 731-day follow-ups.
- The study suggests the need for a larger controlled trial to validate the combination therapy's effectiveness.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** Paxlovid (PubChem CID 155903259)

## Full-text entities

- **Diseases:** fatigue (MESH:D005221), dysautonomia (MESH:D054969), IACCI (MESH:D002908), brain fog (MESH:D005222), LC (MESH:D000094024)
- **Chemicals:** IMC-2 (-), IP (MESH:C041508), Paxlovid (MESH:C000719967)
- **Species:** herpesvirus [taxon 39059], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

23 references — full list in the complete paper: https://tomesphere.com/paper/PMC12812670/full.md

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Source: https://tomesphere.com/paper/PMC12812670