COVID-19 Myocarditis and Severity Factors: An Adult Cohort Study

  1. Kun-Long Ma
  2. Zhi-Heng Liu
  3. Chun-Feng Cao
  4. Ming-Ke Liu
  5. Juan Liao
  6. Jing-Bo Zou
  7. Ling-Xi Kong
  8. Ke-Qiang Wan
  9. Jun Zhang
  10. Qun-Bo Wang
  11. Wen-Guang Tian
  12. Guang-Mei Qin
  13. Lei Zhang
  14. Fu-Jun Luan
  15. Shi-Ling Li
  16. Liang-Bo Hu
  17. Qian-Lu Li
  18. Hai-Qiang Wang

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Abstract

Background

Notwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual’s health conditions; myocarditis incidence rate and hallmarks.

Methods

Demographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors.

RESULTS

In total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008].

Interpretation

T hree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

Research in context

Evidence before this study

We searched Pubmed on March 15, 2020 using the terms (“COVID-19” OR “novel coronavirus” OR “2019 novel coronavirus” OR “2019-nCoV” OR “pneumonia” OR “coronavirus”), AND “Myocarditis” OR “Cycle threshold (Ct)” OR “Altitude”. We found that one article analyzed the risk factors affecting the prognosis of adult patients with COVID-19 in terms of survivorship, without considering Ct values as extrinsic factors. Moreover, there are no reported studies on viral myocarditis caused by COVID-19 and the relationship between the altitude and COVID-19.

Added value of this study

We retrospectively analyzed the clinical data, Ct values, laboratory indicators and imaging findings of 84 adult patients with confirmed COVID-19. Three key-independent risk factors of COVID-19 were identified in our study, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Moreover, altitude should be considered for COVID-19 severity classification, given that oxygen partial pressure and blood oxygen saturation of regional patients vary with altitudes.

Implications of all the available evidence

T hree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.19.20034124: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Ethics Review Committee of Yongchuan Hospital (No. 2020KLS-6).
    Consent: We obtained oral informed consent for involved patients and/or their relatives.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Continuous (means for normally distributed variables and/or interquartile ranges for abnormally distributed variables) and categorical variables (percentage, %) were analyzed using SPSS, version 29.0.
    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:
    There are some limitations in our study. Firstly, the sample size in our study was relatively small, only 84 patients were included. The deadline of the collected data was March 2, 2020, with 16 patients still hospitalized. Secondly, we did not get exact viral load of patients as viral copy numbers due to the urgent outbreak of COVID-19 and limited conditions. We used Ct values as a substitute. Nevertheless, the results of multivariable logistic regress model demonstrated that the Ct value of SARS-CoV-2 is valid and reliable. Thirdly, we diagnosed four cases of viral myocarditis clinically, without evidence of cardiac biopsy as the gold standard of diagnosis. The echocardiography and cardiac MRI were unavailable due to limited protective measures. However, we strictly excluded the interference of the patient’s cardiac history, and made a clinical diagnosis based on the clinical manifestations of myocardial injury, high levels of cardiac enzymes and cTn I, as well as typical ECG changes, which were consistent with the most updated diagnostic criteria of viral myocarditis.12,13

    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 55. 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.

    About SciScore

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  2. Version published to 10.1101/2020.03.19.20034124v1 on medRxiv