The testis is among the male organs with the highest expression of angiotensin-converting
enzyme 2 (ACE2), particularly in Sertoli cells, Leydig cells, spermatogonia,
spermatocytes and spermatids; therefore, the possibility of SARS-CoV-2 infection spread
to the testis and of a direct damage to testicular endocrine function and spermatogenesis
is not a negligible aspect. In addition, the possibility of indirect testicular damage
has been suggested; indeed, orchitis has been reported in patients with SARS-CoV-2,
favored by the activation of a systemic inflammatory response to SARS-CoV-2 infection,
and changes in gonadotropin levels that support the presence of subclinical or
compensated hypogonadism associated with SARS-CoV-2 infection have been highlighted,
although the possibility of effects mediated by the inflammatory state, the use of
corticosteroids or stress cannot be excluded. Controversial data are available regarding
the possibility that SARS-CoV-2 infection can actually spread to semen, and there is
currently no evidence of a direct association between SARS-CoV-2 infection and male
infertility, although an altered expression of ACE2 has been associated with
non-obstructive azoospermia. The widespread expression of ACE2 by endothelial cells
represents an additional susceptibility alert in relation to the male reproductive
system, as well as to sexual function, in particular for the potential direct and
indirect effects of SARS-CoV-2 infection on the penile vascular endothelium; indeed,
multiple evidences support the presence of a multi-organ endothelial dysfunction in
SARS-CoV-2 infection, connected to the direct tropism of the virus mediated by the
diffuse expression of ACE-2 in endothelial cells, as well as to the systemic inflammation
through the increased production of pro-inflammatory cytokines which mediate/favor the
alteration of the function and permeability of the vascular endothelium. In this context,
erectile dysfunction could represent a long-term complication of Covid-19; penile
vascular endothelial dysfunction is indeed recognized as the dominant mechanism in the
onset of vasculogenic erectile dysfunction, and preliminary studies highlight a
significantly higher prevalence of erectile dysfunction in patients with Covid-19,
regardless of other variables affecting erectile function, such as psychological state,
age and body mass index. Anosmia/hyposmia, associated or not with ageusia, has been
frequently reported as a symptom of the onset of SARS-CoV-2 infection, but it could also
remain the only clinical manifestation in some paucisymptomatic patients. The incidence
of anosmia in SARS-CoV-2 patients is around values between 33.9% and 68%, with a
predominance in the female sex. The etiopathogenetic mechanisms underlying the onset of
anosmia in these patients are yet to be fully clarified; the main mechanisms proposed
include damage to olfactory sensory neurons or direct invasion of the brain via the
olfactory bulb. Smell disorders affect nutrition and quality of life with important
psycho-social consequences. In this scenario, it appears of primary importance to
evaluate and monitor the long-term evolution of anosmia in post SARS-CoV-2 infection
through an objective assessment.

The aim of the study is to investigate whether in male patients recovered from COVID-19
disease, SARS-CoV-2 infection has induced: 1) alterations of seminal parameters (oligo-,
astheno-, teratozoospermia, azoospermia, necrozoospermia, leukocytospermia, hypo /
hyperposia); 2) hypogonadism; 3) morpho-structural alterations of the testis evaluated by
ultrasonography (testicular hypotrophy, testicular and / or epididymal inhomogeneity,
testicular calcifications / microlithiasis, testicular solid lesions, hydrocele,
varicocele, altered testicular and / or epididymal vascularization); 4)
prostate-vesicular morpho-structural alterations assessed by ultrasonography; 5)
morpho-structural and hemodynamic alterations of the penis evaluated by ultrasonography
with Color and PowerDoppler performed at baseline, and in some selected cases which will
be identified as pathological at baseline, also performed dynamically after
intra-cavernous infiltration of prostaglandin-E1 (PGE1) (morphological alterations,
nodules, alterations of the albuginea tunic, presence of fibrotic or calcified plaques,
morphological and haemodynamic alterations of the cavernous arteries, anastomosis between
the cavernous arteries and the dorsal artery, presence of other collateral circulation,
presence and site of any occlusions); 6)male sexual dysfunctions (erectile dysfunction,
premature ejaculation, hypoactive sexual desire disorder) assessed by sexological
questionnaires. Moreover, the aim of the study is also to investigate whether in male and
female patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced an
olfactory dysfunction, with evaluation of the eventual correlation between prevalence,
severity, duration and possible permanence of olfactory dysfunction and the severity of
the COVID-19 disease, using the Sniffin 'Sticks test for the evaluation of: odor
threshold (T), odor discrimination (D) and odor identification (I) (TDI score).

Patients will be evaluated at baseline (at discharge from infectious and/or pneumology
unit) and after 3- 12 months.