Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome

  1. Ann Monaghan
  2. Glenn Jennings
  3. Feng Xue
  4. Lisa Byrne
  5. Eoin Duggan
  6. Roman Romero-Ortuno

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Abstract

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres ® NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25–78; 74% women), of which 56 (66%) reported OI during AS (OI AS ). OI AS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HR nadir : 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HR nadir was the only OI AS predictor (OR = 1.09, 95% CI: 1.01–1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOH AS ) orthostatic hypotension, but neither correlated with OI AS . Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OI tilt ). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOH tilt (2 to HR > 120 bpm), but six did not report OI tilt . In conclusion, OI AS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OI AS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

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  1. Version published to 10.3389/fphys.2022.833650
  2. ScreenIT

    SciScore for 10.1101/2021.12.19.21268060: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participants were eligible for inclusion under all the following criteria: (1) age 18 years or older; (2) history of confirmed or suspected SARS-CoV-2 infection; (3) experiencing prolonged symptoms such as fatigue; (4) able to mobilise independently (with or without aid); (5) able to transfer independently or with minimal assistance of one person from lying to standing; and (6) able to give informed consent.
    IRB: Statistical significance was defined as P<0.05. 2.8 Ethical approval: This study received full approval by the St James’s Hospital/Tallaght University Hospital Joint Research Ethics Committee (Submission Number: 104: TROPIC; Approval Date: 4 May 2021) and the St James’s Hospital Research & Innovation Office (Reference: 6566; Approval Date: 14 May 2021).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.1 Study and cohort description: This was a cross-sectional observational study on a participant cohort recruited for the TROPIC (Technology assisted solutions for the Recognition of Objective Physiological Indicators of post-Coronavirus-19 fatigue) investigation at Trinity College Dublin and St James’s Hospital Dublin, Ireland.
    Trinity
    suggested: (Trinity, RRID:SCR_013048)
    We utilised the SPSS Chart Builder to visualise hemodynamic differences between subgroups via cluster line chart with representation of 95% confidence intervals (CI) around means.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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 has limitations. Firstly, from a study design perspective, generalisability of the findings cannot be assumed given the non-probabilistic recruitment. The evidence we presented is cross-sectional and observational, hence causation cannot be inferred. In addition, we did not have a sample of controls, which can be beneficial in the study of long COVID (Amin-Chowdhury and Ladhani, 2021). Statistical underpower is likely, given the many instances where the statistic of choice for comparisons was the Fisher’s exact test, and a small sample size that precluded inclusion of a greater number of predictors in the regression models. Another limitation is that our testing protocol did not include other standardised autonomic tests such as heart rate variability with paced breathing or blood pressure response to Valsalva maneuver. However, in the same clinical environment, Townsend et al. performed those tests on a different long COVID cohort and reported negative findings (Townsend et al., 2021). Our study did not have more detailed measures of baroreflex function, or any imaging or biomarker information (e.g., hematological, biochemical, immunological). For ethical approval reasons, in some cases our research tilts had to be stopped sooner (e.g., with only mild symptoms) than is often the case for tilts used in clinical practice to look for full symptom reproduction. From a haemodynamic data processing point of view, other studies have extracted the raw data from the Finapre...

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

    IdentifierStatusTitle
    NCT05027724RecruitingTechnology Assisted Solutions for the Recognition of Objecti…

    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2021.12.19.21268060v1 on medRxiv