Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study.

PURPOSE: While SARS-CoV-2 infection appears not to be clinically evident in the testes, indirect inflammatory effects and fever may impair testicular function. To date, few long-term data of semen parameters impairment after recovery and comprehensive andrological evaluation of recovered patients has been published. The purpose of this study was to investigate whether SARS-CoV-2 infection affect male reproductive health. METHODS: Eighty patients were recruited three months after COVID-19 recovery. They performed physical examination, testicular ultrasound, semen analysis, sperm DNA integrity evaluation (TUNEL), anti-sperm antibodies (ASA) testing, sex hormone profile evaluation (Total testosterone, LH, FSH). In addition, all patients were administered International Index of Erectile Function questionnaire (IIEF-15). Sperm parameters were compared with two age-matched healthy pre-COVID-19 control groups of normozoospermic (CTR1) and primary infertile (CTR2) subjects. RESULTS: Median values of semen parameters from recovered SARS-CoV-2 subjects were within WHO 2010 fifth percentile. Mean percentage of sperm DNA fragmentation (%SDF) was 14.1 ± 7.0%. Gelatin Agglutination Test (GAT) was positive in 3.9% of blood serum samples, but no positive semen plasma sample was found. Only five subjects (6.2%) had total testosterone levels below the laboratory reference range. Mean bilateral testicular volume was 31.5 ± 9.6 ml. Erectile dysfunction was detected in 30% of subjects. CONCLUSION: Our data remark that COVID-19 does not seem to cause direct damage to the testicular function, while indirect damage appears to be transient. It is possible to counsel infertile couples to postpone the research of parenthood or ART procedures around three months after recovery from the infection.

Proceedings of the VI National Meeting of the Italian Group of Paleopathology (GIPaleo)

The presence of numerous scientific contributions in the program is certainly demonstrative of the fact that research in the field of paleopathology and anthropology has not stopped since the beginning of Covid-19. Furthermore, the same emergency that we are still partially feeling, has pushed our community scientific research to question itself more intensely in connection to the epidemic relationship and measures that repeatedly led to profound transformations in the societies of the past from different points of view: demographic, economic, social and the history buried under the bioarchaeological strata is today more capable than ever to show this connection. It can do this by bringing to light the paleodemographic data that is obtained from the study of human remains. Today we will listen to many paleopathological stories and among these I am very happy to also present ours. Twenty years ago, the University of Insubria started a collaboration with the Archaeological Superintendence of Lombardy for the study of osteological remains found mostly during emergency archaeology recoveries. These experiences led us to reach those bioarchaeological sites again with the aim of extracting all those cemetery layers that remained there because they were not subjected at that time by building reclamation interventions. Returning to those sites that in the past brought to light fragmentary anthropological data means allowing oneself the possibility of obtaining new palaeodemographic and palaeopathological data which are decisive for reconstructing the demographic and epidemiological history of the populations of the past. These new interventions led us to create an operational model that immediately intended to underline the importance of an evident continuity between the archaeological recovery and the anthropological study of the finds through the setting up of physical anthropology and paleopathology laboratories directly on the sites of the finds. All this in harmony with the final design of the projects or the museumization of bioarchaeological sites in their complexity aimed at enhancing cultural tourist routes in the area. In this regard, I would like to thank the community foundation of Varese and the Cariplo foundation for supporting our current initiatives. These include the project financed by the emblematic provincial tender and which has as its final objective the enhancement of three bioarchaeological sites in Valcuvia: the medieval sites of San Biagio in Cittiglio, Sant’Agostino in Caravate, and the modern crypt of the church of the Convent of Azzio. Today, our Research Centre works in Piedmont in different sites in the province of Vercelli and Alessandria. Aware of the importance of a physical anthropological approach in the field, our young Centre goes beyond the continental borders to reach Eritrea, the ancient city of Adulis, because it is in dissecting the taphonomic events and the funeral actions that will make it possible to identify the funerary ritual adopted by the ancient populations. The operational model of paleopathological research, which gradually enriches itself thanks to the multidisciplinary nature of the interventions and thanks to the individual experiences in the field, is thus continuously transferred and adapted to other anthropological contexts that retain potential both in terms of investigative and enhancement of the bioarchaeological heritage. Through the musealization of the sites it is also possible to acquire an attractive force towards all those potentially bioarchaeological areas but which today are in conditions of neglect because they are marginal with respect to the conventionally understood cultural tourist good. And we all know how important it is to transfer the study data even outside the academic context because making this aspect of archaeology, the truly human one, usable too, cannot fail to arouse a strong awareness of our past. We also know how much more we will have to work, following in the footsteps of the professors who started this path, to ensure that the d sciplines of paleopathology and physical anthropology arrive within all those degree courses still discovered today by these teachings to heal an important lack: knowing the human past from a physical and pathological point of view allows us to understand the evolutionary path of some pathologies, especially those of infectious nature. If my title of the speech “Paleopathology and osteoarchaeology in the province of Varese” does not respond to what is being said today, it is because my feeling about paleopathology and osteoarchaeology in the province of Varese is understood as that of carrying out research, what I could feel everywhere, through the operational model, the enthusiasm for paleopathological research and of course the people I am lucky enough to work with. The Morgagni Museum of Pathological Anatomy of the University of Padua preserves a wide series of pathological specimens, mostly from the second half of the 19th century and the early 20th century. The Museum was recently renewed, as the result of an intervention of enhancement of the museum and cultural heritage of the University of Padua and its Medical School, being also testimony to the history and evolution of human pathology and past population lifestyle. In the collection of the Morgagni Museum there are several specimens affected by atherosclerotic lesions. Atherosclerosis is characterized by a chronic inflammatory disease in which different factors are involved, such as lipoproteins, immune cells and endothelial damage. The main clinical syndromes related to atherosclerosis are angina pectoris, acute myocardial infarction, transient ischemic attack, cerebral stroke, intermittent claudication, aortic aneurysm and nephro-vascular hypertension. Atherosclerosis was believed to be a modern disease, related almost exclusively to age and current lifestyle. The cases from the Morgagni Museum are therefore useful for studying the presence of the atherosclerosis in a recent past population. In the collection there were identified six atherosclerotic cases: an atherosclerotic aneurysm of the ascending aorta: the specimen highlights the left ventricular outflow tract and the aortic root. There is a severe atherosclerosis of the ascending aorta with saccular aneurysm including a large thrombus;a syphilitic aortitis complicated by atherosclerosis: the finding highlights the left ventricular outflow tract and aortic root. It is possible to note the intima of the ascending aorta with ulcer-calcific atherosclerotic plaques and “tree-bark” whitish areas;an atherosclerotic aneurysm of the abdominal aorta: abdominal aorta with saccular atherosclerotic aneurysm, proximal to the iliac bifurcation;a case of aortic atherosclerosis: aorta with severe atherosclerosis complicated by calcification and thrombosis;a case of aortic atherosclerosis: massive dissemination of atheromatous-calcific plaques;a case of aortic atherosclerosis with parietal thrombi: widespread presence of plaques along the aortic wall. Thanks to this collection, it is possible to notice the spread of pathology on an atheromatous basis in the recent past populations. Moreover, current paleopathological investigations on ancient populations mummified remains also showed traces of atherosclerotic lesions in both sexes and different ages. It is therefore possible to support a ubiquitous diffusion in space and time of this complex multifactorial pathology which has so far considered to be almost an exclusive prerogative of old age and current lifestyle. The Morgagni Museum of Pathological Anatomy of the University of Padua, founded by Lodovico Brunetti (1813-1899) in the 1860s, gathers important pathological specimens mainly from the 19th century. Among them, there is a very peculiar preparation: it consists of a dried head representing a case of argyria dating back to 1873. The specimen is preserved in a sealed jar, all the skin has a blue-gray coloration with white-blonde hair and beard. The eyes are not preserved, but since the ocular cavities remain open, it is possible to presume that origin lly there were glass eyes. Two glass sticks are inserted inside the mouth to show that also tongue and gums have the same blue-gray pigmentation as the face. The upper teeth are strongly eroded. Argyria is a rare disease caused by chronic absorption of products with a high silver content, which surpass body’s renal and hepatic excretory capacities, leading to silver granules being deposited in the skin and its appendages, mucosae and internal organs. It is characterized by blue-gray or black staining of the skin and mucous membranes. Our case was first mentioned in 1862 as a syphilitic man who was treating himself with some caustic silver nitrate, the so called “infernal stone”, since 1840s. According to him, this medicament cured the syphilis, but turned him into a “graphite man”. The patient died in 1873 of an intestinal infection, most likely related to the prolonged ingestion of the silver nitrate. This case was described as “spectacular” by Austrian dermatologist Isidor Neumann (1832-1906), who studied a sample of the tongue of the specimen sent by Brunetti. In fact, Brunetti performed the autopsy on the body of the individual and prepared also a plaster cast of the head along with the sample for Neumann. Thus, we can assume Brunetti was also the one who preserved the original head, taxidermizing it (so-called stuffed head preparation) in order to preserve the skin color, because his famous tannisation method would not maintained the original characteristics. Human taxidermy is quite rare, and it is limited to a few cases in the 19th century. Moreover, there are just a few known human stuffed heads in the world, making the Paduan specimen particularly unique both for the pathology and the technique used for the preparation.

Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

Molecular diagnosis of SARS-CoV-2 in seminal fluid.

PURPOSE: Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. METHODS: A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - "Sapienza" University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank "Loredana Gandini'' of the same hospital. RESULTS: The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with Ct values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. CONCLUSION: These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation.

SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità).

PURPOSE: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) METHODS: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria. RESULTS: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects. CONCLUSION: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

Sperm cryopreservation during the SARS-CoV-2 pandemic.

PURPOSE: Sperm cryopreservation is fundamental in the management of patients undergoing gonadotoxic treatments. Concerns have risen in relation to SARS-CoV-2 and its potential for testicular involvement, since SARS-CoV-2-positive cryopreserved samples may have unknown effects on fertilization and embryo safety. This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. METHODS: We recruited 10 cancer patients (mean age 30.5 ± 9.6 years) referred to our Sperm Bank during the Italian lockdown (from March 11th to May 4th 2020) who had not undergone a nasopharyngeal swab for SARS-CoV-2 testing. Patients were administered a questionnaire on their exposure to COVID-19, and semen samples were taken. Before cryopreservation, SARS-CoV-2 RNA was extracted from a 150 µl aliquot of seminal fluid in toto using QIAamp viral RNA kit (Qiagen) and amplified by a real time RT PCR system (RealStar SARS-CoV2 RT PCR, Altona Diagnostics) targeting the E and S genes. RESULTS: The questionnaire and medical interview revealed that all patients were asymptomatic and had had no previous contact with COVID-19 infected patients. All semen samples were negative for SARS-CoV-2 RNA. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation.

Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab.

INTRODUCTION: The recent appearance of SARS-CoV-2 in Wuhan in 2019 has started a pandemic which has involved over a million people worldwide. A matter of debate is the possible viral detection in different body fluids than respiratory droplets. Thus, we evaluated the possible presence of SARS-CoV-2 in semen and urine samples of a volunteer with confirmed COVID-19. MATERIALS AND METHODS: A 31-year-old man with fever, myalgia, anosmia, and ageusia was tested and found positive for SARS-CoV-2 through a pharyngeal swab. Eight days after he provided semen and urine samples in which viral RNA presence was measured using a Real time RT PCR system (RealStar SARS-CoV-2 RT-PCR, Altona Diagnostics) targeting E and S viral genes. RESULTS AND DISCUSSION: Semen and urine samples search for SARS-CoV-2 RNA was negative. Although this should be interpreted cautiously, it may be possible that either the viral clearance kinetics in these matrices matches the progressive clinical recovery of the patient or that the virus was never present in these fluids at the time of the laboratory diagnosis.