Discussion
The administration of heparin was associated with lower mortality in patients admitted with Covid-19. This study has strengths and limitations. Patients were not randomized and the difference in outcome may be explained by factors other than the treatment with heparin. In an effort to control for the severity of disease, or the effects of other drugs, the models were adjusted for clinical markers and other treatments. The observation of a large number of unselected patients in 17 hospitals, and the analyses run with some variations to test the consistency of the results, are also strengths of this study. However, residual confounding is always present in all observational research. For all models the sensitivity analyses described in the methods were used to assess the impact of missing data on the two severity markers, and results were consistent with those presented.
While the nature of the hypoperfusion of lungs in Covid-19 patients is still not fully understood, our findings support that there is a thrombotic component in the development of respiratory distress for these patients [6, 8]. The association between heparin and survival is consistent with the findings of an observational study where among the 99 patients who received heparin, and had a sepsis-induced coagulopathy index > 4, mortality was significantly lower [12]. A recent observational study conducted in a hospital has also reported lower mortality among the 786 Covid-19 patients who received anticoagulation [13].
To the best of our knowledge, there is no interventional evidence on the management of the coagulopathy associated with Covid-19. The positive effect of heparin seems consistent and its use, when indicated, could be considered in clinical settings. Randomized controlled trials are necessary to complement observational studies, and assess the causal associations between heparin, in different therapeutic regimes, and clinical outcomes. Heparin is easy to administer, its use in ambulatory patients, to prevent admissions, or reduce their duration, could also be considered by clinicians and future researchers.