key: cord-0955885-ysjj8fed
authors: Mondaini, Nicola
title: Phosphodiesterase Type 5 Inhibitors and COVID-19: Are They Useful In Disease Management?
date: 2020-06-04
journal: World J Mens Health
DOI: 10.5534/wjmh.200089
sha: d0ef61f2e16c9229394235710b07d2f8291d2fe3
doc_id: 955885
cord_uid: ysjj8fed

nan

this reason, patients with diabetes who already have a damaged endothelium are probably more sensitive to the effects of COVID-19 [4] .

Patients with diabetes often also have erectile dysfunction, which is nothing more than endothelial dysfunction, and in such patients, the use of phosphodiesterase-5 (PDE5) inhibitors is recommended to treat erectile dysfunction. Thus, like diabetes, the presence of erectile dysfunction could also represent a symptom to be taken into consideration when predicting the prognosis of patients with COVID-19. This possibility points to a potential role of PDE5 inhibitors in the management of COVID-19 [5] . The PDE5 inhibitor sildenafil citrate is a vasodilator that was approved in 1998 for treating erectile dysfunction and more recently received an indication for pulmonary arterial hypertension and idiopathic pulmonary fibrosis [6] . Sildenafil is currently under investigation in a phase 3 trial in patients with COVID-19 (NCT04304313), which will help clarify its therapeutic potential [5] . The goal of sildenafil treatment is to prevent or perhaps block the progression of fibrosis and to improve respiratory parameters in patients. Tadalafil has also shown www.wjmh.org PDE5 inhibition with an IC 50 of 5 nM. It possesses high selectivity for PDE5 versus PDE1-4 and PDE6. In particular, tadalafil is more selective against PDE5 than PDE6, whereas sildenafil shows similar potency to inhibit PDE5 and PDE6 [7] . Theoretically, the once-daily use of tadalafil, which is a long acting drug, could be useful to improve tissue vascularization and to combat fibrosis. Tadalafil is probably less effective in the acute phase, but could lend itself to use once daily for possible prevention in patients with erectile dysfunction who are not interested in sexual activity, and for similar purposes it could be administered to all discharged patients recovering from COVID-19.

For this reason, daily tadalafil could be a possible post-infection treatment, as its pharmacokinetic parameters, such as half-life and efficacy, make it an ideal candidate. No clear evidence exists regarding the possibility of SARS-CoV-2 infection in the testes, where sclerosis could result in fertility problems.

Therefore, my suggestion is to evaluate the use of daily tadalafil in future trials to block or prevent endothelial sclerosis in COVID-19 patients.

Endothelial cell infection and endotheliitis in COVID-19

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis

Delivering benefits at speed through real-world repurposing of off-patent drugs: the COVID-19 pandemic as a case in point

A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis

Tadalafil: 15 years' journey in male erectile dysfunction and beyond

The author has nothing to disclose.