As the acute phase of the COVID-19 pandemic recedes, another challenge has emerged: a wave of persistent symptoms affecting millions worldwide, collectively known as Long COVID. Among them, a less-discussed but deeply distressing issue has gained clinical attention: erectile dysfunction (ED). What makes this particularly complex is that post-COVID ED does not always follow the typical patterns of aging-related or psychogenic dysfunction. In many cases, it appears linked to lingering vascular and endothelial injury caused by the virus itself. A growing body of research now implicates SARS-CoV-2-induced endothelial dysfunction in the pathogenesis of erectile difficulties among otherwise healthy men after COVID-19 infection. Small-vessel damage, impaired nitric oxide (NO) signaling, and reduced blood flow have been observed not only in penile tissue but across multiple vascular beds, even months after infection.
This vascular perspective has opened the door to therapeutic strategies beyond psychological counseling or traditional PDE5 inhibitors used on demand. One such option is tadalafil 5 mg daily, a low-dose regimen already approved for both erectile dysfunction and benign prostatic hyperplasia (BPH). Its endothelial-stabilizing properties make it a candidate for post-COVID ED management.
In this article, we review the latest science behind COVID-19–associated endothelial injury, explore how tadalafil may counteract this dysfunction, and evaluate what clinical evidence currently supports its use in men struggling with sexual symptoms long after viral recovery.
Endothelial Injury in Long‑COVID and Erectile Dysfunction
Today, COVID-19 is no longer seen as merely a respiratory disease. Increasingly, it is understood as a systemic vascular disorder, with SARS-CoV-2 inflicting lasting damage on the endothelium the thin layer of cells lining blood vessels. This damage has emerged as a plausible contributor to a spectrum of Long-COVID symptoms, including persistent erectile dysfunction (ED). A landmark study published in Andrology provided some of the earliest direct evidence: penile tissue from men with post-COVID ED showed viral particles on electron microscopy, reduced expression of endothelial nitric oxide synthase (eNOS), and signs of severe microvascular dysfunction (Kresch et al., 2021). These findings suggest that COVID-19 can disrupt erectile function by impairing endothelial-mediated vasodilation, a critical mechanism for achieving and maintaining erections.
Further supporting this, autopsy studies and imaging in Long-COVID patients show persistent endothelial activation, vascular inflammation, and altered blood flow patterns well beyond the acute phase of infection. In the genital vasculature, such changes may reduce penile perfusion, degrade nitric oxide signaling, and blunt the responsiveness to sexual stimulation.
Importantly, erectile dysfunction is now considered one of the early warning signs of systemic endothelial pathology, a finding echoed during the pandemic as younger men without prior cardiovascular risk factors reported new-onset ED post-infection.
This mechanistic link between COVID-induced microvascular injury and erectile difficulties positions endothelial repair as a logical therapeutic target. It also raises an important clinical question: can drugs that support vascular function, like PDE5 inhibitors, mitigate the lingering vascular consequences of COVID-19 and restore erectile performance?
We explore that question in the next section by examining the mechanistic rationale for daily tadalafil use in post-COVID ED.
Mechanistic Rationale for PDE5 Inhibitors Post‑COVID
The physiology of penile erection is exquisitely sensitive to endothelial health. Under normal conditions, sexual stimulation activates nitric oxide (NO) release in the penile endothelium, which in turn promotes cyclic guanosine monophosphate (cGMP) production, a signaling cascade that relaxes smooth muscle and increases blood flow. The enzyme phosphodiesterase type 5 (PDE5) degrades cGMP, thereby limiting vasodilation. This is where PDE5 inhibitors like tadalafil come in: by inhibiting PDE5, they sustain cGMP levels, enhancing erection quality and duration. However, the benefits of PDE5 inhibitors extend well beyond the penis. In fact, tadalafil’s vascular actions are systemic, and this has new relevance in the context of COVID-19. The SARS-CoV-2 virus has been shown to disrupt endothelial integrity, impair NO synthesis, promote oxidative stress, and increase vascular stiffness, which are factors that all contribute to erectile dysfunction (ED) and broader cardiovascular strain. Tadalafil 5 mg daily has been shown in multiple studies to reduce endothelial inflammation and oxidative damage, improve NO-mediated vasodilation, and even stimulate endothelial progenitor cells involved in vascular repair (Shamohammadi et al., 2024). These properties make it more than just a symptomatic therapy; it may act as a functional endothelium stabilizer, especially important for men recovering from viral-induced vascular injury.
In patients with diabetes and metabolic syndrome, conditions that similarly feature endothelial dysfunction, daily tadalafil has shown improvements in flow-mediated dilation (FMD) and arterial compliance. It also modestly reduces C-reactive protein (CRP) and endothelin-1, markers of systemic inflammation and vasoconstriction, respectively. These observations are now being extended to the Long-COVID population, where similar vascular impairments persist.
Another unique advantage of once-daily dosing is its non-dependence on sexual planning. For men whose libido or confidence is still recovering, daily low-dose therapy provides continuous vascular support, removing the psychological burden of timed medication and potentially improving compliance and outcomes.
Ultimately, in the setting of Long-COVID related ED, daily tadalafil may serve dual roles: enhancing erectile response through direct vasodilation, while addressing the root cause—impaired endothelial function. This mechanistic plausibility is now being tested in clinical trials and real-world studies, which we explore in the following section.
Clinical Evidence: Does Daily Tadalafil Help Post‑COVID ED?
Early studies suggest that daily 5 mg tadalafil may be effective in treating erectile dysfunction linked to Long COVID, especially where endothelial dysfunction is suspected. A randomized, placebo-controlled trial published in the Asian Journal of Urology enrolled 78 men with post-COVID ED and assigned them to receive tadalafil 5 mg daily or placebo for 12 weeks (Shamohammadi et al., 2024). The tadalafil group saw a mean IIEF-5 improvement of 6.4 points, compared to 1.9 in the placebo group. Sexual confidence and satisfaction also improved significantly.
In an observational study from Minerva Urology and Nephrology, 52 men taking tadalafil after COVID-19 reported better erections, reduced fatigue, and improved mood over six months (Zaghloul, 2024). Penile duplex results showed enhanced blood flow, supporting the drug’s vascular effect.
Across studies, side effects were mild and expected. They included headache, flushing, or nasal congestion with no serious adverse events reported.
While these data are early and limited in scope, they point toward real potential for tadalafil in this population, especially for men with signs of vascular impairment and no contraindications to PDE5 inhibitors.
Broader Context & Emerging Insights
The interest in daily tadalafil for post-COVID erectile dysfunction doesn’t exist in a vacuum. Since 2020, there’s been a marked increase in the global use of low-dose PDE5 inhibitors, partly driven by anecdotal reports of post-COVID sexual symptoms and rising awareness of the condition’s vascular impact. A 2021 study noted a surge in sales of ED medications including tadalafil during the pandemic, particularly among younger men with no prior urologic history (Hernandez, 2021). This trend may reflect both increased stress-related dysfunction and growing use of PDE5 inhibitors for recovery support in Long COVID cases.
Another reason for tadalafil’s appeal is its once-daily convenience and potential to restore spontaneity in sexual activity, which on-demand dosing cannot offer. Clinicians are increasingly considering daily tadalafil not just for symptomatic relief, but also as a supportive therapy for endothelial recovery.
Conclusion and Research Directions
Erectile dysfunction following COVID-19 is more than a quality-of-life issue. It may be an early indicator of persistent endothelial dysfunction and microvascular injury, especially in younger men without traditional cardiovascular risk factors. The current evidence suggests that tadalafil 5 mg daily, already approved for ED and BPH, holds promise as a dual-action therapy in this setting: improving erectile performance while potentially supporting vascular repair.
Preliminary studies show encouraging outcomes like improved IIEF scores, better penile blood flow, and enhanced well-being, with few side effects and excellent tolerability. These benefits, combined with tadalafil’s once-daily dosing and systemic vascular effects, make it an appealing option for post-COVID recovery, even though it remains off-label for this indication.
That said, significant gaps remain. Larger, multicenter randomized controlled trials are urgently needed to confirm efficacy and assess long-term safety. Future studies should also explore objective vascular biomarkers, compare daily vs. on-demand regimens, and investigate benefits in other Long COVID domains, such as fatigue or cognitive function, where endothelial repair may also play a role.
For now, clinicians should consider individual risk profiles, symptom patterns, and patient preference when discussing treatment.
References
- Hernandez, I. (2021). Marked increase in sales of erectile dysfunction medications during the COVID-19 pandemic. Journal of General Internal Medicine, 36(10), 3045 3047. https://doi.org/10.1007/s11606-021-06968-2
- Zaghloul, A. S. (2024). The impact of long-term COVID-19 infection on patients’ erectile function and the therapeutic role of daily tadalafil 5 mg: A prospective study. Minerva Urology and Nephrology. https://doi.org/10.1177/03915603241237402
