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Review 2: "Virtual reality exercise to help COVID patients with refractory breathlessness"

This preprint evaluates whether a virtual reality-based rehabilitation program could improve breathing comfort in patients recovering from COVID-19 and found this iVR-based DTx treatment protocol was effective. Reviewers rated the study as potentially informative but confounded.

Published onJan 25, 2022
Review 2: "Virtual reality exercise to help COVID patients with refractory breathlessness"
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key-enterThis Pub is a Review of
Virtual reality exercise to help COVID patients with refractory breathlessness

SummaryBackgroundImmersive virtual reality (iVR)-based digital therapeutics (DTx) are gaining clinical attention in the field of pain management. Based on known analogy between chronic pain and dyspnea, we investigated the effects of visual respiratory feedback in iVR, on refractory breathlessness in patients recovering from severe COVID-19 pneumonia.MethodsWe performed a controlled, randomized, single-blind, cross-over clinical study to evaluate an iVR-based intervention to alleviate refractory breathlessness in patients recovering from COVID-19 pneumonia. The single-site study was conducted at the university hospital of Geneva, Switzerland. Patients reported refractory breathlessness (≥5 on a 10-point dyspnea scale) and had a MoCA score of ≥24. Cross-over groups were randomly assigned, concealed from the referring clinician. Participants received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched avatar in iVR. Prior to the first exposure and following both experimental conditions, patients completed questionnaires. Breathing patterns were captured continuously. The COVVR clinical study is registered with (NCT04844567) and is now closed.FindingsStudy enrollment was open between November 2020 and April 2021. A total of 26 patients (27% women; age: mean=57, SD±12) were enrolled; 14 patients were randomly assigned to the “synchronous/asynchronous” sequence, 12 to the “asynchronous/synchronous” sequence. Data was available for all except two (7.7%) of 26 patients. The mean rating of breathing comfort was 0.1 at baseline, 0.8±1.8 for asynchronous, and 1.3±1.4 synchronous feedback (estimated difference of 0.5 (95%CI 0.05 to 1.04; p<0.05) between iVR conditions). Of all patients, 91.2% were satisfied with the intervention (1.8±1.6, t=5.201, p<0.0001, 95%CI 1.173 to inf) and 66.7% perceived it as beneficial for their breathing (0.7±1.9, t=1.806, p<0.05, 95%CI 0.036 to inf). No adverse events were reported.InterpretationBased on these findings, we propose that our iVR-based DTx is a feasible and safe neuro-rehabilitation tool that improves breathing comfort in patients recovering from severe COVID-19 infection. More research is needed to generalize this tool in other groups of patients suffering from refractory breathlessness.FundingMarie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2019 894111/ RESPVR), Bertarelli Foundation

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



The current submission includes a controlled, single-blind, cross-over clinical study focused on evaluating an immersive virtual reality setup (iVR) to improve clinical conditions of 26 patients with Covid-19 pandemic outcomes and pneumonia with refractory breathlessness (RB). Two experimental conditions were assessed, namely (a) synchronous and (b) asynchronous. Outcomes were assessed through self-reports evaluated on a 7 point Likert scale. Results evidenced 91% of participants' satisfaction by using the IVR setup. Furthermore, 66% perceived a breathing positive effect (i.e., it was considered beneficial). Therefore, the iVR setup was considered an effective, suitable, and feasible technological tool in clinical settings.

I found the paper interesting, relevant, and appropriate. However, I feel that some relevant issues should be addressed in a suitable revision. My concerns are listed below.

1. Even if panel research in the context, evidence before the study, and an added value were presented, I feel that a concise overview of the current literature on the specific topic should be provided in the Introduction section, and a strong rationale should be further provided and argued.

2. The authors stated that randomization was not restricted. No stratification or minimization factors were applied. However, both sentences are unclear to me. Were the participants randomly and systematically assigned to the experimental conditions? Clarification is needed.

3. Participants' characteristics, currently missing based o my reading, should be detailed and fully included either in a narrative way or summarized in a synoptic table, depending on authors' discretion.

4. Table and Figures layout should be improved.

5. I would include the limitations that the current investigation was based on self-reports. An objective and direct observation of the breath cycles would be preferable or, at least, necessary.

6. Future research perspectives, currently missing, should be added.

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