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Another new application of heparin in COVID-19: more than anticoagulation and antiviral
  1. Xianqiang Yu
  1. Medical School, Southeast University–Dingjiaqiao Campus, Nanjing, Jiangsu, China
  1. Correspondence to Dr Xianqiang Yu, Medical School, Southeast University–Dingjiaqiao Campus, Nanjing, Jiangsu 210009, China; yuxianqiang302{at}

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Dear Editor,

We read with great interest an article in your journal about the relationship between heparin dose and anticoagulation effect of COVID-19 infection.1 As the pandemic continues to spread and challenge, it is particularly important to standardize treatment protocols for COVID-19 anticoagulation. To the best of our knowledge, heparin-binding protein (HBP) has important clinical value as an early predictor of COVID-19 and its combination with heparin plays a key role in anticoagulant therapy.2 In particular, the latest reports have unprecedentedly confirmed the anti-inflammatory mechanism of heparin in sepsis. From this perspective, heparin may play a double-edged sword effect in the anti-inflammatory and anticoagulant effects of severe COVID-19.

It is reported that heparin inhibited HMGB1–lipopolysaccharide interactions and prevented macrophage heparinase from degrading glycocalyx.3 HMGB1 is a well-studied component of the damage-associated molecular pattern family. As a key potential therapeutic target in the occurrence and development of sepsis, it has always been the target of drug exploration. It is well known that heparin is a pluripotent drug for clinical favor, including anticoagulant, lipid-lowering, anti-inflammatory, and so on. But to be clear, little is known about the mechanism by which heparin exacts its anti-inflammatory effects. We also noted that even if the anticoagulant part of heparin was removed, it could also play a significant anti-inflammatory effect in sepsis through the HMGB1 pathway. In other words, modified heparin can be used in inflammatory diseases without concern for its classical pharmacological side effects. Severe COVID-19 is often faced with a combination of severe inflammation and coagulation disorders. In particular, elevated HBP levels in patients with severe COVID-19 provide the possibility of carrying exogenous heparin. Therefore, from this point of view, heparin has multiple clinical values of anticoagulation and anti-inflammatory in the treatment of severe COVID-19. We have noted that there are currently a series of randomized controlled trials of heparin in the treatment of COVID-19 anticoagulants. Therefore, the next focus should be to consider which patients with COVID-19 will benefit from heparin treatment, which will not, and which may even be impaired. With this in mind, the appropriate range of heparin in the treatment of patients with COVID-19 and the balance of its anticoagulant and anti-inflammatory doses are urgently needed to be clarified.

As the pandemic continues to spread and brings uncertain risks, targeted intervention drugs for severe COVID-19 are of far-reaching significance. In particular, heparin, as a potentially effective anti-inflammatory agent in severe patients, combined with its own anticoagulant effect may play a significant role in the treatment of severe COVID-19. The clarity of the anti-inflammatory mechanism of heparin through HMGB1 pathway gives us sufficient confidence in its potential anti-inflammatory value in patients with severe COVID-19. After all, there is reason to be optimistic about heparin as a new trial for an old drug.

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  • Contributors XY completed the design and writing of the article and all the relevant contents of the manuscript.

  • Funding This study was funded by Scholarship of Southeast University (No 189351).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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