madman
Super Moderator
Introduction
COVID-19, the coronavirus disease caused by SARS-CoV-2, is an unprecedented issue for healthcare: the rapid spread of the different viral strains, the lack of universally viable treatments, and the high prevalence of patients requiring intensive care contributed to a large number of casualties worldwide. As of September 30th, 2021, the World Health Organization has estimated over 4,7 million deaths for COVID-19 among more than 232 million cases [1]. This is largely suggestive of the largely variable clinical phenotype of the disease [2], with the vast majority of patients having contracted SARS-CoV-2 being asymptomatic, or having only mild symptoms [3,4] during the acute phase of the disease.
As new evidence started piling up, it became increasingly apparent that long-term chronic complications of COVID-19 were to be expected [5]. These complications, initially greeted with skepticism by many physicians, were defined as “long COVID” on social media [6], while from a more pathophysiological basis, they would more appropriately be defined as “post-acute” or “chronic”, according to the duration and onset [7]. At present, a growing body of evidence supports the notion that some patients might develop long-term, multiorgan complications of COVID-19 which may affect the patients’ quality of life and result in long-lasting disability, or increased vulnerability to other conditions. In fact, only some patients with COVID develop long-term complications, suggesting the idea that the presence of several risk factors, including demographic and lifestyle factors [8], the severity of the underlying infection and the resulting duration of in-patient stay, and prior health conditions could overexpress the effects of COVID infection for a longer period. Dyspnea, fatigue, and anxiety are among the chief complaints of COVID long-haulers; however, other residual effects of SARS-CoV-2 have been identified in more recent reports. This condition has been defined by the National Institute for Health and Care Excellence (NICE) as the persistence of symptoms occurring during or after SARS-CoV-2 infection in the absence of any other possible medical explanation [9], and by the NIH and CDC (National Institutes of Health and Centers for Disease Control, respectively) as all COVID-19 sequelae persisting beyond four weeks after the onset of disease [10].
COVID-19 affects many organs and systems, largely owing to the almost ubiquitous expression of the angiotensin-converting enzyme 2 (ACE2) receptor allowing internalization of the virus in target cells [11]. According to current evidence, SARS-CoV-2 invades endothelial cells through ACE2 and transmembrane protease serine 2 (TMPRSS2) [12], and the resulting endothelial damage has been investigated as one of the main features of the immunological hyper-response associated with worse outcomes for acute COVID-19 [13]. It is therefore largely expected that the same organs targeted by SARS-CoV-2 may be affected by long COVID [14], therefore providing a plausible explanation for its variable clinical phenotype.
This finding makes COVID-19 a relevant condition for sexual medicine experts, with the involvement of the endothelium in erectile function [15] being only the most obvious reason for concern [16]. Sexual function for patients with acute COVID-19 has barely been investigated, also owing to the disease severity; however, the persisting endothelial dysfunction occurring in long COVID might become a relevant issue for many individuals, made even more worrisome by the prevalence of the “post-acute COVID-19 syndrome” among younger individuals and by the possible interaction between different organic and non-organic mechanisms of action.
*This review aims to investigate and highlight the mechanisms through which long-term consequences of COVID-19 can affect erectile function, also discussing the current evidence concerning the epidemiology of long COVID and the potential treatments, wherever available.
*Neuropsychiatric complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Respiratory complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Cardiovascular complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Endocrine complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Other long-term complications of COVID-19
Conclusions and future directions
COVID-19 is a typical viral, obviously transmissible disease where social behavior, i.e., lifestyle, plays a major role. In fact, the clinical impact of the COVID -19 is largely based on age and on the presence of comorbidities with chronic, non-communicable diseases (NDCs), which are also largely dependent on lifestyles. Finally, the seriousness of the long COVID itself is very frequently, but not always, proportional to the presence and to the severity of NCDs. These findings are highly relevant in the context of sexual medicine, owing to the shared risk factors for sexual dysfunctions (particularly concerning ED) and COVID-19: several factors could contribute to the onset of sexual health issues in COVID patients, including endothelial dysfunction, prolonged hypoxia due to respiratory impairment, anxiety and depression, and endocrine disorders.
Taken together, all these aspects could be featured in a sexual long COVID (SLC) syndrome, which may not only have a pathophysiological and taxonomic value but could also act as a biomarker of the clinical impact of the “general” long COVID. As ED is a widely accepted clinical biomarker of cardiovascular and general health [183–185], it makes sense to hypothesize SLC as a clinical biomarker of long COVID, once again highlighting the relevance of sexual function outside the boundaries of sexual medicine. Plenty of evidence, in fact, clarifies how sexual health is lost at the earliest stages of chronic diseases and belatedly recovered in the process of complete healing. In this light, SLC might become the clinical biomarker of all systemic underlying factors featured in long COVID (figure 1): patients who develop symptoms of the SLC might indeed have worse risk profiles concerning all other complications of long COVID compared to those who maintain a good erectile function. Erectile disorders might therefore be a clinically tangible warning of the complex web of underlying vascular, endothelial, metabolic, neuropsychiatric, and pulmonary risk factors [186]. This is also supported by the bidirectional relationship existing between COVID-19 and ED, suggesting not only that COVID-19 patients are more likely to develop ED, but also that, owing to the shared risk factors, the odds ratio for developing COVID-19 is much higher in men having worse erectile function [186,187].
Another possible merit of the taxonomic introduction of the SLC could be education. It is well known that arguments related to sexual health may have a much higher psychological impact on shifting from wrong behavioral habits to healthy lifestyles. This is particularly true for young people, a group peculiarly interested in sexual health and, unfortunately, still reluctant to vaccinate [187,188]. The ghost of SLC may help in the double effort to educate to get vaccinated and to improve healthy behaviors. “No vax, no sex” could become, in this light, a tremendously powerful motivational claim.
Hence, a flow such as that proposed in figure 2 may highlight the mentioned relationships, which, once again, represent the role of lifestyles in the development of sexual dysfunctions dependent on both communicable (as COVID-19) and non-communicable diseases (as NCDs, increasing the COVID19-related risks).
Future studies should be addressed at identifying the prevalence of ED among long COVID patients, using both validated questionnaires, such as the International Index of Erectile Function [189,190], and specific diagnostic tests, including dynamic duplex ultrasound of the penis [191]. These studies will provide much-needed evidence concerning the extent to which erectile function is affected by long COVID and the exact mechanics behind this impairment. Additionally, more studies might be considered in order to measure whether patients developing SLC following the acute phase of the disease show worse outcomes for cardiovascular, respiratory, or neurologic function, compared to those who did not incur into any sexual dysfunction – once again suggesting a clinical phenotype in which erection is the “tip of the iceberg” of more systemic dysfunction.
At present, despite the piling up evidence concerning the long-term complications of COVID-19, sexual health has drawn little attention from the medical community; however, as erectile function is among the most reliable mirrors of a man’s overall health [184,185], also possibly predicting cardiovascular events [184,185], we strongly believe it is time to investigate more systematically the sexual function of COVID-19 long haulers.
COVID-19, the coronavirus disease caused by SARS-CoV-2, is an unprecedented issue for healthcare: the rapid spread of the different viral strains, the lack of universally viable treatments, and the high prevalence of patients requiring intensive care contributed to a large number of casualties worldwide. As of September 30th, 2021, the World Health Organization has estimated over 4,7 million deaths for COVID-19 among more than 232 million cases [1]. This is largely suggestive of the largely variable clinical phenotype of the disease [2], with the vast majority of patients having contracted SARS-CoV-2 being asymptomatic, or having only mild symptoms [3,4] during the acute phase of the disease.
As new evidence started piling up, it became increasingly apparent that long-term chronic complications of COVID-19 were to be expected [5]. These complications, initially greeted with skepticism by many physicians, were defined as “long COVID” on social media [6], while from a more pathophysiological basis, they would more appropriately be defined as “post-acute” or “chronic”, according to the duration and onset [7]. At present, a growing body of evidence supports the notion that some patients might develop long-term, multiorgan complications of COVID-19 which may affect the patients’ quality of life and result in long-lasting disability, or increased vulnerability to other conditions. In fact, only some patients with COVID develop long-term complications, suggesting the idea that the presence of several risk factors, including demographic and lifestyle factors [8], the severity of the underlying infection and the resulting duration of in-patient stay, and prior health conditions could overexpress the effects of COVID infection for a longer period. Dyspnea, fatigue, and anxiety are among the chief complaints of COVID long-haulers; however, other residual effects of SARS-CoV-2 have been identified in more recent reports. This condition has been defined by the National Institute for Health and Care Excellence (NICE) as the persistence of symptoms occurring during or after SARS-CoV-2 infection in the absence of any other possible medical explanation [9], and by the NIH and CDC (National Institutes of Health and Centers for Disease Control, respectively) as all COVID-19 sequelae persisting beyond four weeks after the onset of disease [10].
COVID-19 affects many organs and systems, largely owing to the almost ubiquitous expression of the angiotensin-converting enzyme 2 (ACE2) receptor allowing internalization of the virus in target cells [11]. According to current evidence, SARS-CoV-2 invades endothelial cells through ACE2 and transmembrane protease serine 2 (TMPRSS2) [12], and the resulting endothelial damage has been investigated as one of the main features of the immunological hyper-response associated with worse outcomes for acute COVID-19 [13]. It is therefore largely expected that the same organs targeted by SARS-CoV-2 may be affected by long COVID [14], therefore providing a plausible explanation for its variable clinical phenotype.
This finding makes COVID-19 a relevant condition for sexual medicine experts, with the involvement of the endothelium in erectile function [15] being only the most obvious reason for concern [16]. Sexual function for patients with acute COVID-19 has barely been investigated, also owing to the disease severity; however, the persisting endothelial dysfunction occurring in long COVID might become a relevant issue for many individuals, made even more worrisome by the prevalence of the “post-acute COVID-19 syndrome” among younger individuals and by the possible interaction between different organic and non-organic mechanisms of action.
*This review aims to investigate and highlight the mechanisms through which long-term consequences of COVID-19 can affect erectile function, also discussing the current evidence concerning the epidemiology of long COVID and the potential treatments, wherever available.
*Neuropsychiatric complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Respiratory complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Cardiovascular complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Endocrine complications of long COVID
-Pathophysiology and prevalence
-Relevance for erectile function
*Other long-term complications of COVID-19
Conclusions and future directions
COVID-19 is a typical viral, obviously transmissible disease where social behavior, i.e., lifestyle, plays a major role. In fact, the clinical impact of the COVID -19 is largely based on age and on the presence of comorbidities with chronic, non-communicable diseases (NDCs), which are also largely dependent on lifestyles. Finally, the seriousness of the long COVID itself is very frequently, but not always, proportional to the presence and to the severity of NCDs. These findings are highly relevant in the context of sexual medicine, owing to the shared risk factors for sexual dysfunctions (particularly concerning ED) and COVID-19: several factors could contribute to the onset of sexual health issues in COVID patients, including endothelial dysfunction, prolonged hypoxia due to respiratory impairment, anxiety and depression, and endocrine disorders.
Taken together, all these aspects could be featured in a sexual long COVID (SLC) syndrome, which may not only have a pathophysiological and taxonomic value but could also act as a biomarker of the clinical impact of the “general” long COVID. As ED is a widely accepted clinical biomarker of cardiovascular and general health [183–185], it makes sense to hypothesize SLC as a clinical biomarker of long COVID, once again highlighting the relevance of sexual function outside the boundaries of sexual medicine. Plenty of evidence, in fact, clarifies how sexual health is lost at the earliest stages of chronic diseases and belatedly recovered in the process of complete healing. In this light, SLC might become the clinical biomarker of all systemic underlying factors featured in long COVID (figure 1): patients who develop symptoms of the SLC might indeed have worse risk profiles concerning all other complications of long COVID compared to those who maintain a good erectile function. Erectile disorders might therefore be a clinically tangible warning of the complex web of underlying vascular, endothelial, metabolic, neuropsychiatric, and pulmonary risk factors [186]. This is also supported by the bidirectional relationship existing between COVID-19 and ED, suggesting not only that COVID-19 patients are more likely to develop ED, but also that, owing to the shared risk factors, the odds ratio for developing COVID-19 is much higher in men having worse erectile function [186,187].
Another possible merit of the taxonomic introduction of the SLC could be education. It is well known that arguments related to sexual health may have a much higher psychological impact on shifting from wrong behavioral habits to healthy lifestyles. This is particularly true for young people, a group peculiarly interested in sexual health and, unfortunately, still reluctant to vaccinate [187,188]. The ghost of SLC may help in the double effort to educate to get vaccinated and to improve healthy behaviors. “No vax, no sex” could become, in this light, a tremendously powerful motivational claim.
Hence, a flow such as that proposed in figure 2 may highlight the mentioned relationships, which, once again, represent the role of lifestyles in the development of sexual dysfunctions dependent on both communicable (as COVID-19) and non-communicable diseases (as NCDs, increasing the COVID19-related risks).
Future studies should be addressed at identifying the prevalence of ED among long COVID patients, using both validated questionnaires, such as the International Index of Erectile Function [189,190], and specific diagnostic tests, including dynamic duplex ultrasound of the penis [191]. These studies will provide much-needed evidence concerning the extent to which erectile function is affected by long COVID and the exact mechanics behind this impairment. Additionally, more studies might be considered in order to measure whether patients developing SLC following the acute phase of the disease show worse outcomes for cardiovascular, respiratory, or neurologic function, compared to those who did not incur into any sexual dysfunction – once again suggesting a clinical phenotype in which erection is the “tip of the iceberg” of more systemic dysfunction.
At present, despite the piling up evidence concerning the long-term complications of COVID-19, sexual health has drawn little attention from the medical community; however, as erectile function is among the most reliable mirrors of a man’s overall health [184,185], also possibly predicting cardiovascular events [184,185], we strongly believe it is time to investigate more systematically the sexual function of COVID-19 long haulers.
