Health-related quality of life in immunocompromised adults with mild–moderate COVID-19 treated with nirmatrelvir-ritonavir: results from the randomized, double-blinded EPIC-IC trial

Abstract Background Little is known about health-related quality of life (HRQoL) in immunocompromised people during and after COVID-19 illness. We describe HRQoL outcomes from the EPIC-IC trial, which included participants with immunocompromise and mild–moderate COVID-19. Methods EPIC-IC was a randomized, double-blind trial. Participants were assigned 1:1:1 to 5-day, 10-day, or 15-day nirmatrelvir-ritonavir (NMV/r) and completed the SF-36 and EQ-5D-5L through Week (W)24. HRQoL was analyzed across and by treatment arms for the evaluable population (N = 150) and in post hoc subpopulations with severe (n = 57) and non-severe (n = 93) immunocompromise. Mixed-effects longitudinal models compared 5-day vs. 10-day or 15-day NMV/r. Results In the overall sample, mean baseline SF-36 domain scores (norm-based; mean = 50, SD = 10) ranged from 35.7 to 44.1, mean Physical Component Summary (PCS) score was 37.9, and mean Mental Component Summary (MCS) score was 41.5 – all substantially worse than cancer comparator norms and age-matched general population (AMGP) norms. Baseline mean EQ-5D-5L Index score was 0.65; participants reported problems with pain/discomfort (90% of participants), usual activities (73%), mobility (50%), anxiety/depression (48%), and self-care (29%). These proportions improved through Day (D)15 (change from baseline [CFB]: − 49%-points for pain/discomfort, − 38%-points usual activities, − 22%-points mobility, − 24%-points anxiety/depression, − 19%-points self-care) and then stabilized. From the earliest post-baseline assessment (EQ-5D-5L: D5, SF-36: D10), all overall-sample outcomes improved significantly (-5D-5p < 0.05), with all mean improvements exceeding published minimum important difference thresholds (SF-36: 2–4-point; EQ-5D-5L Index: 0.03–0.05-point). Mean EQ-5D-5L Index score surpassed AMGP norms from D5 and peaked at D15 (0.21-point CFB). Mean SF-36 outcomes improved through W12; PCS surpassed AMGP norms at W12, while MCS approached but remained below AMGP norms. Improvements were sustained through W24 (W24 CFB: PCS, 10-point; MCS, 8-point; EQ-5D-5L Index, 0.20-point). EQ-5D-5L improvements appeared similar across immunocompromised subpopulations, whereas SF-36 improvements appeared slower and smaller in severely vs. non-severely immunocompromised participants. No significant treatment-arm differences were observed, except lower D10 PCS scores among severely immunocompromised participants treated with 5-day vs. 10-day NMV/r (p = 0.03). Conclusion Immunocompromised individuals with mild–moderate COVID-19 experienced various HRQoL decrements, followed by rapid improvements during treatment that were sustained through W24. Interpretation is limited by the absence of an untreated control group. Clinical trial registration Clinical trial number: NCT05438602. Registry: ClinicalTrials.gov. Registration date: June 28, 2022. URL: https://clinicaltrials.gov/ct2/show/NCT05438602 .