Virtual reality intervention alleviates dyspnea in patients recovering from COVID pneumonia

  1. Betka Sophie
  2. Kannape Oliver Alan
  3. Fasola Jemina
  4. Lance Florian
  5. Cardin Sylvain
  6. Schmid Aline
  7. Similowski Thomas
  8. Soccal Paola Marina
  9. Herbelin Bruno
  10. Adler Dan
  11. Blanke Olaf

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Abstract

Background

Immersive virtual reality (iVR)-based digital therapeutics (DTx) are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnea, we investigated the effects of visual-respiratory feedback, on persistent dyspnea in patients recovering from COVID-19 pneumonia.

Methods

We performed a controlled, randomized, single-blind, cross-over clinical study to evaluate an iVR-based intervention to alleviate dyspnea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnea (≥5 on a 10-point scale) and preserved cognitive function (MoCA>24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. Outcomes were assessed using questionnaires and breathing recordings. COVVR is registered with ClinicalTrials.gov ( NCT04844567 ).

Findings

Study enrollment was open between November 2020 and April 2021. Twenty-six patients were enrolled (27% women; age: median=55, interquartile range (IQR)=18). Data were available for 24 of 26 patients. The median (IQR) rating on a 7-point Likert-scale of breathing comfort improved from 1(2) at baseline, to 2(1) for synchronous feedback, but remained unchanged at 1(1.5) for asynchronous feedback (p<0.05) between iVR conditions). Moreover, 91.2% of all patients were satisfied with the intervention (p<0.0001) and 66.7% perceived it as beneficial for their breathing (p<0.05). No adverse events were reported.

Interpretation

Based on these findings, our iVR-based DTx presents a feasible and safe respiratory rehabilitation tool that improves breathing comfort in patients recovering from COVID-19 infection presenting with persistent dyspnea. Future research should investigate the DTx’s generalizability to persistent dyspnea with other etiologies and its potential for preventing chronification.

Funding

Marie Sklodowska-Curie Individual Fellowship (H2020-MSCA-IF-2019 894111/ RESPVR), Bertarelli Foundation

Article activity feed

  1. Version published to 10.1101/2021.10.26.21265510v2 on medRxiv
  2. Rapid Reviews Infectious Diseases

    Giuseppe Riva

    Review 1: "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.

  3. Rapid Reviews Infectious Diseases

    Fabrizio Stasolla

    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.

  5. ScreenIT

    SciScore for 10.1101/2021.10.26.21265510: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Furthermore, patients had to be able to give consent and to understand and speak French or English.
    Sex as a biological variablenot detected.
    RandomizationStudy Design: A controlled, randomized, single-blind, cross-over clinical study was conducted to evaluate both efficacy and feasibility of a Virtual Reality biofeedback intervention to alleviate RB in patients recovering from severe COVID-19 pneumonia.
    BlindingParticipant masking (blinding) was achieved by keeping both the procedure and the virtual environment identical for both tested conditions.
    Power AnalysisStatistical Analysis: Based on previous work on breathing agency 13, a necessary sample size of 21 patients was estimated, using a two-sided paired t-test with an effect size of 0.65, alpha of 0.05 and a power of 0.8 to demonstrate a difference of 0.5 between the two experimental conditions.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Software developed by the laboratory in collaboration with MindMaze allowed to collect and filter respiratory data and to render a computer-generated virtual environment in real-time.
    MindMaze
    suggested: None
    All analyses were performed using R (version 4.1.0) and Matlab (version 2020a).
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study comes with certain limitations. The main limitation is the small sample size, although it has been based on an adequate power calculation for a proof-of-concept study. Another limitation is that we included only a homogeneous population of patients recovering from severe COVID-19 infection. Our intervention should now be tested in a larger cohort of patients with refractory breathlessness to improve generalizability. Another important unanswered question is whether central desensitization to breathlessness while training with iVR DTx can persist when patients are off-treatment. Longer term studies with breathlessness ecological momentary assessments are therefore needed before such treatment can be widely accepted in a clinical setting. One important innovation this study demonstrates is the improved efficacy linked to real-time biofeedback, going beyond the classically admitted distraction from suffering offered by iVR30. Relying on the recent expansion of Internet of Things (IoT) technologies and of wearable physiological sensors in particular, our approach highlights how iVR DTx interventions can now more specifically target the neural mechanisms of pain and RB. Although in its current form our technology did not fulfill the expectations for home-use in our patients’ cohort, it paves the way for future e-health products that would not only provide monitoring but also a continuum of interventions from hospital bed to patient’s home. In conclusion, our study shows ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04844567RecruitingVirtual Reality Intervention to Alleviate Breathlessness (CO…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  6. Version published to 10.1101/2021.10.26.21265510v1 on medRxiv