Elevated HScore is Associated with Poor Clinical Outcomes in COVID-19, Even in the Absence of Secondary Hemophagocytic Lymphohistiocytosis

  1. Rafael Benavente
  2. Camila Peña
  3. Allyson Cid
  4. Nicolás Cabello
  5. Pablo Bustamante
  6. Marco Álvarez
  7. Elizabeth Henríquez
  8. Andrés Soto
  9. Erika Rubilar

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Abstract

Introduction

Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome, that leads to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. However, it has not been prospectively studied on these patients. A scoring system (HScore) has been validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19.

Methods

143 patients aged ≥18 years admitted because of COVID-19 were enrolled in a prospective, single-center, cohort study. HScore was calculated within the 72 hours since admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between HScore ≥130 points and either the requirement of mechanical ventilation or 60-days mortality was explored.

Results

The median age of enrolled patients was 57 (21-100), and 63.6% were male. The median HScore was 96 (33-169). One patient was diagnosed with sHLH (incidence 0,7%), due to a HScore of 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥130 was independently associated with the composite clinical outcome (HR 2.13, p=0.022).

Conclusion

sHLH is not frequent among COVID-19 patients. HScore can efficiently predict the risk for poor outcomes.

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    SciScore for 10.1101/2021.01.26.21249335: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The study protocol received ethical approval from the institutional ethics committee (Comité de Ética Científica del Servicio de Salud Metropolitano Oriente. Santiago, Chile).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFor the multivariate analysis, a Cox proportional hazards model was used including other reported risk factors for worse outcomes: age, male sex, multiple comorbidities, and obesity.

    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:
    There are some limitations in our study. First, we did not have access to all tests listed in sHLH diagnostic criteria. Namely, NK-lymphocytes study is not currently available in our country; while the soluble CD25 (sCD25) study is not available in our institution. As previously stated, bone marrow study was not performed in all patients, to minimize the researchers’ exposure to the virus, and because it was not considered useful for patient management in most cases. Nevertheless, we believe that we can reasonably rule out sHLH as a cause of hyperinflammation in our patients. Finally, during the data collection, hydroxychloroquine or lopinavir/ritonavir were commonly prescribed, while steroids were not. Data from large RCT have modified this practice [35-36] in favour of steroid use, which in turn could affect the power of HScore to predict poor outcomes. Conclusion: In COVID-19 patients, sHLH seems to be a rare event, but excessive inflammation is common. In our cohort, high HScore (≥130), even at a lower threshold than required for sHLH diagnosis, was associated with poor outcomes. Further studies validating this finding could be helpful to select patients for more aggressive immunosuppressive treatments. The authors declare that they have no conflict of interest.

    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: 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.

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  2. Version published to 10.1101/2021.01.26.21249335v1 on medRxiv