Anakinra in hospitalized COVID-19 patients guided by baseline soluble urokinase plasminogen receptor plasma levels: A real world, retrospective cohort study

PLoS One. 2023 Apr 4;18(4):e0273202. doi: 10.1371/journal.pone.0273202. eCollection 2023.

Abstract

Background: In patients with COVID-19 and baseline soluble urokinase plasminogen receptor plasma (suPAR) levels ≥ 6ng/mL, early administration of anakinra, a recombinant interleukin-1 receptor antagonist, may prevent disease progression and death. In case of suPAR testing unavailability, the Severe COvid Prediction Estimate (SCOPE) score may be used as an alternative in guiding treatment decisions.

Methods: We conducted a monocenter, retrospective cohort study, including patients with SARS-CoV2 infection and respiratory failure. Patients treated with anakinra (anakinra group, AG) were compared to two control groups of patients who did not receive anakinra, respectively with ≥ 6 ng/mL (CG1) and < 6 ng/mL (CG2) baseline suPAR levels. Controls were manually paired by age, sex, date of admission and vaccination status and, for patients with high baseline suPAR, propensity score weighting for receiving anakinra was applied. Primary endpoint of the study was disease progression at day 14 from admission, as defined by patient distribution on a simplified version of the 11-point World Health Organization Clinical Progression Scale (WHO-CPS).

Results: Between July, 2021 and January, 2022, 153 patients were included, among which 56 were treated with off-label anakinra, 49 retrospectively fulfilled prescriptive criteria for anakinra and were assigned to CG1, and 48 presented with suPAR levels < 6ng/mL and were assigned to CG2. At day 14, when comparing to CG1, patients who received anakinra had significantly reduced odds of progressing towards worse clinical outcome both in ordinal regression analysis (OR 0.25, 95% CI 0.11-0.54, p<0.001) and in propensity-adjusted multiple logistic regression analysis (OR 0.32, 95% CI 0.12-0.82, p = 0.021) thus controlling for a wide number of covariates. Sensitivities of baseline suPAR and SCOPE score in predicting progression towards severe disease or death at day 14 were similar (83% vs 100%, p = 0.59).

Conclusion: This real-word, retrospective cohort study confirmed the safety and the efficacy of suPAR-guided, early use of anakinra in hospitalized COVID-19 patients with respiratory failure.

MeSH terms

  • Biomarkers
  • COVID-19*
  • Disease Progression
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Plasminogen
  • RNA, Viral
  • Receptors, Urokinase Plasminogen Activator
  • Respiratory Insufficiency* / chemically induced
  • Retrospective Studies
  • SARS-CoV-2
  • Urokinase-Type Plasminogen Activator

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
  • Plasminogen
  • RNA, Viral
  • Biomarkers

Grants and funding

The author(s) received no specific funding for this work.