A recent study published in International Journal of Impotence Research reports that men previously infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19), are at a greater risk of developing new-onset erectile dysfunction.

Study: Prior COVID-19 infection associated with increased risk of newly diagnosed erectile dysfunction. Image Credit: Antonio Marca / Shutterstock.com

The long term effects of COVID-19

As of April 2022, SARS-CoV-2 infected over 80 million individuals and caused over 970,000 deaths in the United States.

Long-term health consequences of COVID-19, which are collectively referred to as long-COVID, have been widely reported. Real-world evidence shows that people with long-COVID can experience a wide range of symptoms that can last for weeks, months, or even years after acute SARS-CoV-2 infection.

In addition to general symptoms of fatigue, post-exertional malaise, and fever, long-COVID is associated with respiratory, cardiovascular, neurological, digestive, and musculo-skeletal complications. A small number of initial reports have also reported a link between COVID-19 and erectile dysfunction in men, which might be attributed to long-term cardiovascular complications.

Existing literature indicates the persistent presence of SARS-CoV-2 viral particles in corporal tissue, the erectile tissue of the penis, several months after COVID-19 infection. This suggests a possible pathophysiological mechanism for erectile dysfunction in men with a history of COVID-19.

Study design

The IBM MarketScan is a large insurance claims database that includes over 215 million policy holders. In the current study, this database was used to identify men who were diagnosed with COVID-19 between January 2020 and January 2021 and subsequently diagnosed with new-onset erectile dysfunction.

The association between prior COVID-19 and new-onset erectile dysfunction was determined after controlling for common erectile dysfunction risk factors including age, prostate cancer, cardiovascular disease, hypogonadism, obesity, smoking, and diabetes mellitus. Bladder cancer, hypertension, hyperlipidemia, spinal cord injury, and geographic region were included in the analysis as additional covariates.

Important observations

A total of 42,406 men with a history of COVID-19 were included in the study. A total of 45,119 age-matched men without prior COVID-19 were also included as experimental controls in the comparative analysis.

Men with a history of COVID-19 were more likely to have a history of diabetes, hypertension, hyperlipidemia, and hypogonadism as compared to those without COVID-19.

A total of 1,111 cases of new-onset erectile dysfunction were identified between January 2020 and January 2021. Among these cases, 54.1% were men with prior COVID-19 and 45.9% were men without COVID-19. The rates of new-onset erectile dysfunction in the COVID-19 and control groups were 1.4% and 1.1%, respectively.  

After controlling for potential confounding factors like diabetes, cardiovascular disease, smoking, obesity, hypogonadism, thromboembolism, and malignancy, the multivariate analysis showed a significant independent association between previously diagnosed COVID-19 and increased risk of new-onset erectile dysfunction.

Study significance

Men with a history of COVID-19 were at a 27% increased risk of developing erectile dysfunction, which is comparable to a new diagnosis of diabetes following recovery from COVID-19. Existing literature indicates that endothelial dysfunction caused by SARS-CoV-2 infection might be responsible for the development of erectile dysfunction.

Some studies have also highlighted the potential involvement of angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which are human cell membrane proteins responsible for SARS-CoV-2 entry. These proteins are ubiquitously expressed in endothelial cells and might be involved in the pathogenesis of COVID-19-related vasculogenic erectile dysfunction.   

In the IBM MarketScan commercial claims database, medical visits and associated diagnoses are captured longitudinally as long as insurance is billed. This allows for an accurate and adequate capturing of longitudinal patient data, which further reduces the risk of underestimating the effect of prior COVID-19 on erectile dysfunction development.

Since the current study included patient data captured during the initial nine months of the pandemic, the analysis did not consider COVID-19 vaccination, home testing, and SARS-CoV-2 variants as potential confounding factors. Thus, these findings may be more representative of the association between COVID-19 and new-onset erectile dysfunction prior to widespread vaccine uptake, home testing, and variant strain transmission.  

Therefore, future studies with longer follow-up durations are needed to determine whether COVID-19 vaccination can reduce the risk of new-onset erectile dysfunction at the population-level, as well as the variant-specific association between COVID-19 and erectile dysfunction.

COVID-19 home or outpatient tests in which an insurance claim is not submitted are not captured in the IBM MarketScan database. Thus, there remains a possibility that the rate of COVID-19 is underestimated.

Individual medical records are not included in the database; therefore, the researchers could not specifically assess the morbidity associated with each infection. These issues should be considered in future studies to more conclusively understand the impact of COVID-19 on new-onset erectile dysfunction.