To the Editor, The thoughtful and engaging letter from Dr. Li in response to our article, “Recovery of Parosmia Preferentially Influences Longitudinal Improvement of Quality-of-Life in C19OD,” highlights some key findings in our study and raises important considerations regarding the interpretation of our findings, particularly in relation to nuances in quality-of-life (QoL) outcome measures 1. The QOD-NS is a validated instrument specific to olfactory-related QoL and was selected to support the study objective of longitudinally characterizing olfactory recovery and associated changes in QoL among individuals with persistent C19OD. In addition, we assessed general health-related QoL in our study population using the validated EQ-5D instrument 2. In this context, we observed no clinically or statistically meaningful associations between chemosensory domains and EQ-5D outcomes. Prior work evaluating these instruments in this population similarly suggests that the QOD-NS, as an olfactory-specific measure, and the EQ-5D, as a generic utility-based health status measure, are not strongly correlated 3. While both tools assess aspects of QoL, the broad domains captured by the EQ-5D may not adequately reflect the specific and nuanced impact of COVID-associated olfactory dysfunction, for which the QOD-NS is more appropriate. This distinction is particularly important, as highlighted in the letter to the editor, given the multifaceted nature of patient-reported outcomes in long COVID. Accordingly, our study aimed to isolate QoL changes driven by COVID-associated olfactory dysfunction by accounting for potential confounding by comorbid neuropsychiatric conditions, such as depression and anxiety, and chronic medical conditions, such as diabetes, cancer, and kidney disease, among others. Framing the analysis in this olfactory-specific context helps maintain focus on the primary research question without conflating broader contributors to health-related QoL in long COVID, and we appreciate the suggestion that this specificity is not fully captured by the study title. We share the sentiment that an important clinical distinction exists between distorted and reduced smell perception. In this regard, the letter from Dr. Li underscores that recovery from parosmia is likely more directly reflective of meaningful improvement in patient-reported olfactory-specific QoL, whereas improvement in odor discrimination may represent a marker of broader olfactory resolution. To further examine the contribution of discrimination to olfactory-specific QoL, we considered evaluating whether the association between longitudinal changes in discrimination and the QOD-NS remains stable after accounting for baseline QOD-NS severity. While we agree that this is a valuable consideration, we believe that such an analysis would be most appropriately pursued in future work, once sufficient additional follow-up data are available to determine that there is no additional recovery in discrimination in our study population. Finally, cohort composition and baseline phenotype represent important considerations for future analysis. As our longitudinal dataset matures, stratified approaches may help clarify subgroup-specific recovery patterns and further refine the clinical applicability of our findings. We are grateful for the additional thoughtful commentary and dialogue to both reinforce the clinical relevance of the work and highlight key directions for continued investigation. Ongoing dialogue of this kind will be essential to improving patient-centered care in persistent C19OD.
Saak et al. (Wed,) studied this question.