Lung perfusion disturbances in nonhospitalized post‐COVID with dyspnea—A magnetic resonance imaging feasibility study

  1. Jimmy Z. Yu
  2. Tobias Granberg
  3. Roya Shams
  4. Sven Petersson
  5. Magnus Sköld
  6. Sven Nyrén
  7. Johan Lundberg

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Abstract

Background

Dyspnea is common after COVID‐19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea.

Objectives

To detect pulmonary perfusion disturbances in nonhospitalized individuals with the post‐COVID condition and persistent dyspnea 4–13 months after the disease onset.

Methods

Individuals with dyspnea and matched healthy controls were recruited for dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), a 6‐min walk test, and an assessment of dyspnea. The DCE‐MRI was quantified using two parametric values: mean time to peak (TTP) and TTP ratio, reflecting the total lung perfusion resistance and the fraction of lung with delayed perfusion, respectively.

Results

Twenty‐eight persons with persistent dyspnea (mean age 46.5 ± 8.0 years, 75% women) and 22 controls (mean age 44.1 ± 10.8 years, 73% women) were included. There was no systematic sex difference in dyspnea. The post‐COVID group had no focal perfusion deficits but had higher mean pulmonary TTP (0.43 ± 0.04 vs. 0.41 ± 0.03, p = 0.011) and TTP ratio (0.096 ± 0.052 vs. 0.068 ± 0.027, p = 0.032). Post‐COVID males had the highest mean TTP of 0.47 ± 0.02 and TTP ratio of 0.160 ± 0.039 compared to male controls and post‐COVID females ( p = 0.001 and p  < 0.001, respectively). Correlations between dyspnea and perfusion parameters were demonstrated in males ( r = 0.83, p  < 0.001 for mean TTP; r = 0.76, p = 0.003 for TTP ratio), but not in females.

Conclusions

DCE‐MRI demonstrated late contrast bolus arrival in males with post‐COVID dyspnea, suggestive of primary vascular lesions or secondary effects of hypoxic vasoconstriction. Since this effect was not regularly observed in female patients, our findings suggest sex differences in the mechanisms underlying post‐COVID dyspnea, which warrants further investigation in dedicated trials.

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  1. Version published to 10.1111/joim.13558
  2. ScreenIT

    SciScore for 10.1101/2022.01.25.22269717: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical considerations: The Regional Ethics Review Board in Stockholm and the Swedish Ethical Review Authority approved this prospective cross-sectional study performed October 2020 and May 2021 (original approval number 2018/2416-31 with amendments 2020-00047, 2020-02535, 2021-00815).
    Consent: Written informed consent was obtained from all participants.
    Sex as a biological variableOne male person with idiopathic pulmonary fibrosis [24], diagnosed by the Respiratory medicine clinic at Karolinska University Hospital, was additionally included as a positive control.
    Randomizationnot detected.
    BlindingThis was performed by J.Y. and independently verified by J.L., blinded to clinical data.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    MRI perfusion series were analyzed using MATLAB (version R2020b, The Mathworks Inc., Natick, USA) as previously described using an in-house developed post-processing pipeline [18].
    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:
    This study has some limitations, including a lack of other supporting imaging modalities. CT scans would likely detect morphological lung changes with higher sensitivity, but the current MRI protocol was optimized with advanced morphological imaging, including ultra-short echo time imaging that has recently been successfully applied in cystic fibrosis [35]. This study can be regarded as exploratory on the potential use of DCE-MRI in post-COVID, and future studies should combine multiple imaging modalities such as CT, echocardiography, and pulmonary physiological measurements such as spirometry. Nevertheless, we detect heterogeneity in our post-COVID group, indicative of a significant systematic difference on the group level. The heterogeneity supports a possible perfusion problem in the post-COVID group. A technical limitation that is hard to mitigate is the possible contribution of inspiration during breath-hold. A higher degree of inspiration can increase pulmonary resistance by stretching alveolar capillaries and by vessel compression due to higher intrathoracic pressure [36]. Nevertheless, the repeatability of a healthy volunteer was excellent. In addition, the unstructured recruitment of patients through a network of self-identified “long haulers” following COVID-19 could be considered both a weakness and a strength. The potentially increased heterogenicity is offset by a better reflection of clinical reality. In hindsight, with regards to perfusion disturbances detected...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

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

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 19. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

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  3. Version published to 10.1101/2022.01.25.22269717v1 on medRxiv