The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

Dental Prosthesis in Esophagus: A Right Cervicotomic Approach.

Foreign body ingestion in the upper digestive tract is a relatively common emergency. Less than 1% have to be treated surgically. We report the case of a 68-year-old man who ingested a dental prosthesis, probably during a seizure, and thus unknowingly, and presented two days later to the emergency department complaining of a mild dysphagia. A chest radiograph showed the presence of a removable dental prosthesis in the upper esophageal tract. The patient was brought to the operating room where a multidisciplinary equipe was assembled. Two attempts of retrieval with a flexible and a rigid endoscope failed because the removable dental prosthesis was stuck in the right pyriform sinus. Therefore, the surgeon performed an uncommon right cervicotomy and retrieved the foreign body through a right-side esophagotomy. The surgical approach depends on the nature and location of the foreign body. Urgent treatment is required whenever the patient develops dyspnea or dysphagia because of the high risk of inhalation and asphyxia. Removal of any esophageal foreign body has to be performed within 12-24 h. Repeated attempts to retrieve large dental prosthesis using an endoscope may result in esophageal perforation therefore when such risk of complication is too high, a surgical approach becomes inevitable. In our opinion, surgery remains the extrema ratio after a failed endoscopic retrieval attempt but can be lifesaving despite high risk of complications.

Pocket-sized, wireless-Bluetooth ultrasound system to perform diagnostic and low-complexity interventional procedures in bedridden patients during the COVID-19 pandemic: from intensive care unit to domiciliary service?

The use of a pocked-sized, wireless-Bluetooth ultrasound portable system with display images presented on a tablet facilitated the work of our radiologists during the first wave of coronavirus disease 2019 (COVID-19) to perform diagnostic and interventional procedures in bedridden patients. The device is equipped with a battery-powered probe without cables that transmits images to a tablet (or a cell phone) through a dedicated App. We hypothesise in future to extend diagnostic and low-complexity interventional procedures from hospitalised patients to at-home patients who are not able to mobilise out of bed or are difficult to transport. This domiciliary service might also reduce the overhead of hospital accesses.

Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study.

BACKGROUND: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the "bystander effect" and "trained immunity." The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. OBJECTIVE: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. METHODS: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients' vaccination history; and (3) a clinical analysis to detect the immunological profile. RESULTS: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022. CONCLUSIONS: We will recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factor serum levels, and immune cell activity. Anamnestic data, such as preceding vaccinations and comorbidities, biochemical findings like lymphocyte immunophenotyping, and pre-existing persistent cytomegalovirus infection, allow depicting the risk profile of severe COVID-19. Proof of the roles of these immunological phenomena in the development of COVID-19 can be the basis for the implementation of therapeutic immunomodulatory treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04375176; https://clinicaltrials.gov/ct2/show/NCT04375176. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29892.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients.

BACKGROUND: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2. METHODS: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively. FINDINGS: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva. INTERPRETATION: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

Two cases of COVID-19 with positive salivary and negative pharyngeal or respiratory swabs at hospital discharge: A rising concern.

We report two cases of COVID-19 showing negative respiratory swabs but positive salivary samples at the same time. These findings rise the concern about how to manage these patients before hospital discharging, thus avoiding contagion among their family members or a second coronavirus wave once the lockdown is over.

Pilot Study: Long-Term Shedding of SARS-CoV-2 in Urine: A Threat for Dispersal in Wastewater.

Only 4 months after the beginning of SARS-CoV-2 epidemic, the world is facing a global pandemic due to a complex and insidious virus that today constantly poses new challenges. In this study, we highlight a persistent shedding of SARS-CoV-2 RNA into the urine, even in patients with a negative nasopharyngeal swab and in patients considered recovered. What does it mean? Besides the fact that the kidney is a probable site of viral replication, the prolonged viral excretion is a matter of great concern for our drainage system contamination.

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. METHODS: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). RESULTS: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). DISCUSSION/CONCLUSION: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.

Pre-graduation medical training including virtual reality during COVID-19 pandemic: a report on students' perception.

BACKGROUND: The Coronavirus Disease 19 (COVID-19) pandemic brought significant disruption to in-hospital medical training. Virtual reality simulating the clinical environment has the potential to overcome this issue and can be particularly useful to supplement the traditional in-hospital medical training during the COVID-19 pandemic, when hospital access is banned for medical students. The aim of this study was to assess medical students' perception on fully online training including simulated clinical scenarios during COVID-19 pandemic. METHODS: From May to July 2020 when in-hospital training was not possible, 122 students attending the sixth year of the course of Medicine and Surgery underwent online training sessions including an online platform with simulated clinical scenarios (Body Interact™) of 21 patient-based cases. Each session focused on one case, lasted 2 h and was divided into three different parts: introduction, virtual patient-based training, and debriefing. In the same period, adjunctive online training with formal presentation and discussion of clinical cases was also given. At the completion of training, a survey was performed, and students filled in a 12-item anonymous questionnaire on a voluntary basis to rate the training quality. Results were reported as percentages or with numeric ratings from 1 to 4. Due to the study design, no sample size was calculated. RESULTS: One hundred and fifteen students (94%) completed the questionnaire: 104 (90%) gave positive evaluation to virtual reality training and 107 (93%) appreciated the format in which online training was structured. The majority of participants considered the platform of virtual reality training realistic for the initial clinical assessment (77%), diagnostic activity (94%), and treatment options (81%). Furthermore, 97 (84%) considered the future use of this virtual reality training useful in addition to the apprenticeship at patient's bedside. Finally, 32 (28%) participants found the online access difficult due to technical issues. CONCLUSIONS: During the COVID-19 pandemic, online medical training including simulated clinical scenarios avoided training interruption and the majority of participant students gave a positive response on the perceived quality of this training modality. During this time frame, a non-negligible proportion of students experienced difficulties in online access to this virtual reality platform.

Saliva is a reliable tool to detect SARS-CoV-2.

OBJECTIVES: This study analyzed salivary samples of COVID-19 patients and compared the results with their clinical and laboratory data. METHODS: Salivary samples of 25 COVID-19 patients were analyzed by rRT-PCR. The following data were collected: age, sex, comorbidities, drugs. Lactate dehydrogenase (LDH) and ultrasensitive reactive C protein (usRCP) values were registered on the same day when a salivary swab was collected. Prevalence of positivity in saliva and association between clinical data and the cycle threshold as a semiquantitative indicator of viral load were considered. RESULTS: Twenty-five subjects were recruited into this study, 17 males and 8 females. The mean age was 61.5 +/- 11.2 years. Cardiovascular and/or dysmetabolic disorders were observed in 65.22% of cases. All the samples tested positive for the presence of SARS-CoV-2, while there was an inverse association between LDH and Ct values. Two patients showed positive salivary results on the same days when their pharyngeal or respiratory swabs showed conversion. CONCLUSIONS: Saliva is a reliable tool to detect SARS-CoV-2. The role of saliva in COVID-19 diagnosis could not be limited to a qualitative detection of the virus, but it may also provide information about the clinical evolution of the disease.