Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study

Thromb Haemost. 2021 Aug;121(8):1054-1065. doi: 10.1055/a-1347-6070. Epub 2021 Feb 28.


Introduction: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects
  • COVID-19 / blood
  • COVID-19 / complications*
  • COVID-19 Drug Treatment
  • Female
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Hospital Mortality
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Thrombophilia / blood
  • Thrombophilia / etiology*
  • Thrombophilia / prevention & control*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Heparin