Treatment of Long COVID With Enoxaparin

We read with great attention the case report by Wright et al. They report a case of Long COVID treated with enoxaparin, which significantly improved physical and mental function, including specific symptoms such as PEM and orthostatic tachycardia. In this regard, we would like to emphasize that enoxaparin, in addition to its antithrombotic potential, has other relevant effects that could help and justify its use in this type of patient who usually has chronic inflammation and acquired thrombophilia that favors the presence of fibrinaloid microclots. These effects are immunomodulatory—anti-inflammatory potential, antiangiogenic potential, anticomplementemic potential, antitumor potential, and antifibrotic potential.1,2 The combinations of these potential effects in the same drug will probably help treat the complex pathophysiology that surrounds Long COVID and the acquired thrombophilia that determines the multiple symptoms reported in this syndrome. Enoxaparin molecules are known to have nonanticoagulant fractions, which can significantly inhibit T-cell activation, suppressing the release of inflammatory cytokines mainly IL-4, IL-5, IL-13, and TNF-α. Likewise, due to its high degree of sulfation, enoxaparin can interact with small molecules such as histamine, proteins with heparin binding sites (antithrombin and fibronectin), selectins (P and L), adhesion molecules (MAC1 and PECAM-1), platelet integrin αIIbβ3, complement receptors CR3 and CR4, and various growth factors (vascular endothelial and fibroblast-derived, whose coreceptor on the cell surface is heparan sulfate).3,4 All the effects discussed above ensure that enoxaparin is a good therapeutic option; however, it is important to conduct controlled clinical trials that support what was observed in this case report, which is undoubtedly an incentive in the search for a treatment for those affected by Long COVID.