Pentoxifylline and complicated COVID-19: A pathophysiologically based treatment proposal.

To the Editor,

Accumulating evidence suggests that a subgroup of patients with COVID-19 might suffer from severe complications, such as acute respiratory distress syndrome (ARDS), coagulopathy with thromboses and acute cardiac injury, increasing the risk of mortality. A proposed common pathogenetic mechanism for these complications is a SARS-CoV-2-induced proinflammatory state (cytokine storm syndrome-CSS) [1]. Immunomodulatory medications such as inhibitors of interleukin (IL)-6 (tocilizumab) or IL-1 (anakinra) have been proposed as potential treatments for the CSS.

Pentoxifylline (PTX), a non-specific inhibitor of phosphodiesterases and well-established hemorheological factor, exhibits pluripotent properties which could be of value in the context of COVID-19-associated complications. First, PTX inhibits the synthesis of diverse pro-inflammatory cytokines (tumour necrosis factor-α, IL-1, IL-6) and prevents the activation, cell proliferation, adhesion, polarisation and hemotaxis of T cells and neutrophils [2]. Second, PTX antagonizes the inhibitory effect of TNF-α on surfactant synthesis by human type II pneumocytes, which is a pivotal mechanism of ARDS pathogenesis [3]. Third, PTX inhibits platelet aggregation and promotes the fibrinolytic activity, which might decrease the risk of thromboses [4]. Fourth, it exerts cardioprotective actions mediated by its beneficial hemorheological, anti-platelet and anti-inflammatory properties [5]. Its antiviral activity against SARS-CoV-2 has not been tested, but PTX exerts potent in vitro activity against HIV, herpes simplex virus, rotavirus and tick-borne encephalitis virus [6].

To our opinion, this profile of actions of PTX is identically harmonized with several levels of the pathophysiology of COVID-19-associated complications, justifying its trial for the prevention or treatment of severe COVID-19.

Funding sources

The article has no funding source.

Prior presentation

No data from this manuscript were presented in a scientific meeting before.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.