Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells.

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.

Proviral role of human respiratory epithelial cell-derived small extracellular vesicles in SARS-CoV-2 infection.

Small Extracellular Vesicles (sEVs) are 50-200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu-sEVs) produced by human nasal epithelial cells (HNECs) in SARS-CoV-2 infection. We show that uninfected HNECs produce mu-sEVs containing SARS-CoV-2 receptor ACE2 and activated protease TMPRSS2. mu-sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an 'open' conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu-sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS-CoV-2 virions prone to entry into target cells using the 'early', TMPRSS2-dependent pathway instead of the 'late', cathepsin-dependent route. These results indicate that prefusion Spike priming by mu-sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS-CoV-2 infection, but instead facilitates it.

Online Public Interest in Urological Cancers During the COVID-19 Pandemic: What Can "Dr. Google" Teach Us?

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected health care priorities. OBJECTIVE: To explore and analyse trends in public online search for urological cancers. DESIGN SETTING AND PARTICIPANTS: We performed a retrospective analysis using the Google Health Trends online tool. Data related to urological cancer terms ("prostate cancer", "kidney cancer", and "bladder cancer") were extracted. We analysed trends for the whole world and for five countries: Italy, the UK, France, Sweden, and the USA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A join-point regression model was used to define significant changes in trends over time. Week percentage changes (WPCs) were estimated to summarise linear trends. The Mann-Whitney test was used to compare the search volume during the COVID-19 pandemic period (from January 2020 to April 2021) and the equivalent period of 2018 and 2019. RESULTS AND LIMITATIONS: During COVID-19, worldwide online interest decreased significantly for all urological cancers, especially prostate cancer (WPC: -13.9%, p = 0.004; WPC: -5.4%, p < 0.001; and WPC: -4.3%, p < 0.001, for prostate, kidney, and bladder cancers, respectively). The most important decline was observed in the USA. The interest for all cancers was significantly less during the COVID-19 pandemic than in the same periods of 2018 and 2019. CONCLUSIONS: Online interest in urological cancers decreased significantly during the COVID-19 pandemic. Future studies will tell us whether this will translate into worse oncological outcomes. PATIENT SUMMARY: Patients are increasingly searching the Internet to get information on cancer. We explored Google queries during the COVID-19 pandemic and found that online interest decreased significantly for all urological cancers, especially prostate cancer. We do not know yet whether this will translate into worse prognosis for patients.

Impact of the COVID-19 pandemic on oncological and functional robotic-assisted surgical procedures.

The COVID-19 pandemic led to a decrease in surgical activity to avoid nosocomial contamination. Robotic-assisted surgery safety is uncertain, since viral dissemination could be facilitated by gas environment. We assessed the impact and safety of the COVID-19 pandemic on robotic-assisted surgery. Data were collected prospectively during lockdown (March 16th-April 30th 2020) in 10 academic centres with robotic surgical activity and was compared to a reference period of similar length. After surgery, patients with suspected COVID-19 were tested by RT-PCR. During the COVID-19 lockdown we evidenced a 60% decrease in activity and a 49% decrease in oncological procedures. However, the overall proportion of oncological surgeries was significantly higher during the pandemic (p < 0.001). Thirteen (7.2%) patients had suspected COVID-19 contamination, but only three (1.6%) were confirmed by RT-PCR. The COVID-19 pandemic resulted in a significant decrease in robotic-assisted surgery. Robotic approach was safe with a low rate of postoperative COVID-19 contamination.

Preliminary assessment of patient and physician satisfaction with the use of teleconsultation in urology during the COVID-19 pandemic.

PURPOSE: Lockdown during the COVID-19 pandemic compelled urologists to change access to healthcare, especially for oncology patients. Teleconsultation is a safe way to receive medical advice without a risk of infection, and was implemented urgently in our academic centres. Our purpose was to evaluate patient and physician satisfaction with teleconsultation set up during the COVID-19 pandemic. METHODS: From March 16th 2020, all face-to-face consultations were cancelled in France, except for emergencies. Teleconsultation was started immediately by five senior urologists in two academic hospitals. All patients received an email survey including the validated Teleconsultation Satisfaction Questionnaire (TSQ) and demographic questions. Data were collected prospectively. Physicians also responded to the TSQ. Patient satisfaction was measured objectively with the validated 14-item TSQ. Each item was scored on a 5-point Likert scale. Factors associated with positive satisfaction with teleconsultation were assessed by multivariable logistic regression. RESULTS: Overall, 105 patients replied to the survey (91.3%). Median age was 66 years (IQR: 55‒71) and 95 were men (90.5%). Median overall TSQ score was 67 (IQR: 60‒69); teleconsultation was judged to be a good experience by 88 patients (83.8%) and four physicians (80%). Patients who met their surgeon for the first time were more likely to have a good experience (OR = 1.2 [95% CI 1.1‒1.5], p = 0.03). CONCLUSION: Introduced rapidly during the COVID-19 lockdown, urology teleconsultation attained a high level of satisfaction among both patients and physicians. A major change in telemedicine use is foreseen in the post COVID-19 era.