High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial

Abstract

Background: Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms.

Methods: In this placebo-controlled, double-blind, 2 × 2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for 6 weeks, with crossover treatment after a 4-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the 6-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment.

Findings: From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods - 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43.06 (95% CI: 40.18; 45.94), and the mean EQ-5D health index was 0.66 (95% CI: 0.64; 0.68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0.01; 95% CI: -0.02; 0.04; p = 0.45) or the change in PCC-related symptom score (with a mean difference of -1.18; 95% CI: -3.54; 1.17; p = 0.32).

Interpretation: Based on self-reported data, CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo. However, we observed a significant spontaneous improvement on both scores regardless of treatment during 20 weeks observation.

Funding: Placebo and CoQ10 capsules were provided by Pharma Nord, and the trial was supported by grants from the Novo Nordisk Foundation (NNF21OC0066984). This trial is registered with EudraCT, 2020-005961-16 and ClinicalTrials.gov, NCT04960215. The trial is completed.

Conflict of interest statement

We declare no competing interests.

© 2022 The Author(s).

Figures

Fig. 1

Outline of the study design and trial profile. a) Schematic illustration of the study design. The solid circles indicate the five timepoints for completing the questionnaires. b) Flow diagram showing the number of participants at each stage of the trial.

Fig. 2

Heatmap of PCC-specific symptom scores throughout the study period. Heatmap of mean PPC-specific symptom scores for each visit for the participants in arm A (left) and arm B (right). The questionnaire contains 32 questions regarding PCC symptoms, which were graded for severity from 0 to 4 (higher scores indicate more severe symptoms). Boxes at the bottom indicate the treatment periods.

Fig. 3

Time course of PCC-specific symptom scores and EQ-5D health index. Time course of mean PCC-specific symptom scores (a) and mean EQ-5D health index scores (a) reported by the participants in arm A (black circles) and arm B (blue squares) at the indicated time points. The boxes indicate treatment regimen at the two treatment periods.

Fig. 4

Results of the mixed-effects model analysis for seven symptom groups derived from the PCC-specific questionnaire. The mean regression coefficients (slopes) with a 95% confidence interval are plotted to visualize the difference in the change in symptom scores between CoQ10 and placebo. A negative slope indicates a larger reduction in the symptom score with CoQ10 compared to placebo; the dotted vertical line at 0.0 indicates no difference between CoQ10 and placebo. None of the estimated difference in the symptom groups reached statistical significance.