Cardiac impairment in Long Covid 1-year post SARS-CoV-2 infection

  1. A Roca-Fernandez
  2. M Wamil
  3. A Telford
  4. V Carapella
  5. A Borlotti
  6. D Monteiro
  7. H Thomaides-Brears
  8. A Dennis
  9. R Banerjee
  10. M D Robson
  11. G Y H Lip
  12. S Bull
  13. M Heightman
  14. N Ntusi
  15. A Banerjee

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Abstract

Background

Long Covid is associated with multiple symptoms and impairment in multiple organs [1]. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiovascular magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid.

Purpose

We conducted a prospective, longitudinal, 1-year study in individuals with Long Covid to investigate 1) the characteristics and trajectory of cardiac impairment; 2) the impact of acute hospitalisation for COVID-19 on cardiac impairment; and 3) pathways for designing and improving clinical management for individuals at risk of cardiac impairment.

Methods

534 individuals with Long Covid underwent baseline CMR (quantitative T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms. If abnormal findings were reported at baseline, individuals were rescanned at 12.6 months (IQR 11.4, 14.2) (n=330). Symptoms, standardised questionnaires, and blood samples were collected at both timepoints (Figure 1). Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), impaired left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac independent AHA segments. A significant change over time was reported by comparison with 92 healthy controls.

Results

The technical success of this multiorgan assessment in a non-acute setting was 99.1% at baseline, and 98.3% at follow-up, with 99.6% and 98.8% for CMR, respectively. Of individuals with Long Covid, 19% had cardiac impairment at baseline; 70% had complete paired data at 12 months. Of those with paired data, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and reduced GLS were associated with cardiac impairment; however, while elevated T1 was associated with less symptom severity at 12 months, individuals with low LVEF at baseline were associated with ongoing cardiac impairment 1 year post-infection (Figure 2).

Conclusion

Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Radical (EU) and Innovative UK (UK national) (and others)

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  1. Version published to 10.1093/eurheartj/ehac544.219
  2. ScreenIT

    SciScore for 10.1101/2022.04.03.22272610: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participants gave written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Strengths and Limitations: This is the largest longitudinal study to-date of cardiac impairment in Long COVID with detailed biochemical and imaging characterisation of multi-organ function starting in April 2020. We included healthy, age-matched controls. All MRI was non-contrast. We recruited a real-world cohort at lower risk of COVID-19 severity and mortality. Unlike other studies(10), our approach offers quick, scalable assessment using standard MRI scanners. There are limitations. First, our CMR protocol excluded gadolinium contrast due to concerns regarding COVID-19-related renal complications, relying on native non-invasive T1 mapping to characterise myocardial inflammation, validated for acute myocarditis(31). Second, we did not have follow-up scans on individuals without impairment at baseline. Third, we did not have pre-COVID cardiac or multi-organ imaging available in participants. Third, our study population was not ethnically diverse, and COVID-19 has disproportionately affected non-white individuals. Conclusion: CMR shows that cardiac impairment persists in Long Covid in some individuals up to 12 months after first symptoms. Cardiac impairment is associated with acute COVID-19 hospitalisation and male gender, but subtypes of disease (based on symptoms, examination, and investigations) are yet to be established. Therapeutic options and effective clinical pathways require urgent clinical trials.

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

    IdentifierStatusTitle
    NCT04369807Active, not recruitingMapping Organ Health Following COVID-19 Disease Due to SARS-…

    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.

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  3. Version published to 10.1101/2022.04.03.22272610v1 on medRxiv