Social Determinants Contribute to Disparities in Test Positivity, Morbidity and Mortality: Data from a Multi-Ethnic Cohort of 1094 GU Cancer Patients Undergoing Assessment for COVID-19

Background: The COVID-19 pandemic exploits existing inequalities in the social determinants of health (SDOH) that influence disease burden and access to healthcare. The role of health behaviours and socioeconomic status in genitourinary (GU) malignancy has also been highlighted. Our aim was to evaluate predictors of patient-level and neighbourhood-level factors contributing to disparities in COVID-19 outcomes in GU cancer patients. Methods: Demographic information and co-morbidities for patients screened for COVID-19 across the Mount Sinai Health System (MSHS) up to 10 June 2020 were included. Descriptive analyses and ensemble feature selection were performed to describe the relationships between these predictors and the outcomes of positive SARS-CoV-2 RT-PCR test, COVID-19-related hospitalisation, intubation and death. Results: Out of 47,379 tested individuals, 1094 had a history of GU cancer diagnosis;of these, 192 tested positive for SARS-CoV-2. Ensemble feature selection identified social determinants including zip code, race/ethnicity, age, smoking status and English as the preferred first language-being the majority of significant predictors for each of this study's four COVID-19-related outcomes: a positive test, hospitalisation, intubation and death. Patient and neighbourhood level SDOH including zip code/ NYC borough, age, race/ethnicity, smoking status, and English as preferred language are amongst the most significant predictors of these clinically relevant outcomes for COVID-19 patients. Conclusion: Our results highlight the importance of these SDOH and the need to integrate SDOH in patient electronic medical records (EMR) with the goal to identify at-risk groups. This study's results have implications for COVID-19 research priorities, public health goals, and policy implementations.

The Evolving Clinical Management of Genitourinary Cancers Amid the COVID-19 Pandemic.

Coronavirus disease-2019 (COVID-19), a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages throughout the world. There is a high incidence of infection and mortality among cancer patients with evidence to support that patients diagnosed with cancer and SARS-CoV-2 have an increased likelihood of a poor outcome. Clinically relevant changes imposed as a result of the pandemic, are either primary, due to changes in timing or therapeutic modality; or secondary, due to altered cooperative effects on disease progression or therapeutic outcomes. However, studies on the clinical management of patients with genitourinary cancers during the COVID-19 pandemic are limited and do little to differentiate primary or secondary impacts of COVID-19. Here, we provide a review of the epidemiology and biological consequences of SARS-CoV-2 infection in GU cancer patients as well as the impact of COVID-19 on the diagnosis and management of these patients, and the use and development of novel and innovative diagnostic tests, therapies, and technology. This article also discusses the biomedical advances to control the virus and evolving challenges in the management of prostate, bladder, kidney, testicular, and penile cancers at all stages of the patient journey during the first year of the COVID-19 pandemic.

COVID-19 in patients with and without cancer: Examining differences in patient characteristics and outcomes.

This study examines differences between patients with and without cancer in patient demographic and clinical characteristics and COVID-19 mortality and discusses the implications of these differences in relation to existing cancer disparities and COVID-19 vulnerabilities. Data was collected as a part of a retrospective study on a cohort of COVID-19 positive patients across Mount Sinai Health System from March 28, 2020 to April 26, 2020. Descriptive, comparative, and regression analyses were applied to examine differences between patients with and without cancer in demographic and clinical characteristics and COVID-19 mortality and whether cancer status predicts COVID-19 mortality controlling for these covariates using SAS 9.4. Results showed that, of 4641 patients who tested positive for COVID-19, 5.1% (N=236) had cancer. The median age of the total sample was 58 years (Q1-Q3: 41-71); 55.3% were male, 19.2% were current/former smokers, 6.1% were obese. The most commonly reported comorbidities were hypertension (22.6%) and diabetes (16.0%). Overall, the COVID-19 mortality rate was 8.3%. Examining differences between COVID-19 patients with and without cancer revealed significant differences (p<0.05) in COVID-19 mortality, hospitalization rates, age, gender, race, smoking status, obesity, and comorbidity indicators (e.g., diabetes) with cancer patients more likely to be older, male, black, obese, smokers, and with existing comorbidities. Controlling for these clinical, demographic, and behavioral characteristics, results of logistic regression analyses showed significant effects of older age and male gender on COVID-19 mortality (p<0.05). While cancer patients with COVID-19 were more likely to experience worse COVID-19 outcomes, these associations might be related to common cancer and COVID-19 vulnerability factors such as older age and gender. The coexistence of these vulnerability age and gender factors in both cancer and COVID-19 populations emphasizes the need for better understanding of their implications for cancer and COVID-19 disparities, both diseases prevention efforts, policies, and clinical management.

A COVID-19 Test Triage Tool, Predicting Negative Results and Reducing the Testing Burden on Healthcare Systems During a Pandemic.

Background: Detecting and isolating cases of COVID-19 are amongst the key elements listed by the WHO to reduce transmission. This approach has been reported to reduce those symptomatic with COVID-19 in the population by over 90%. Testing is part of a strategy that will save lives. Testing everyone maybe ideal, but it is not practical. A risk tool based on patient demographics and clinical parameters has the potential to help identify patients most likely to test negative for SARS-CoV-2. If effective it could be used to aide clinical decision making and reduce the testing burden. Methods: At the time of this analysis, a total of 9,516 patients with symptoms suggestive of Covid-19, were assessed and tested at Mount Sinai Institutions in New York. Patient demographics, clinical parameters and test results were collected. A robust prediction pipeline was used to develop a risk tool to predict the likelihood of a positive test for Covid-19. The risk tool was analyzed in a holdout dataset from the cohort and its discriminative ability, calibration and net benefit assessed. Results: Over 48% of those tested in this cohort, had a positive result. The derived model had an AUC of 0.77, provided reliable risk prediction, and demonstrated a superior net benefit than a strategy of testing everybody. When a risk cut-off of 70% was applied, the model had a negative predictive value of 96%. Conclusion: Such a tool could be used to help aide but not replace clinical decision making and conserve vital resources needed to effectively tackle this pandemic.

Increased Hospitalization and Mortality from COVID-19 in Prostate Cancer Patients.

BACKGROUND: Cancer patients with COVID-19 have a poor disease course. Among tumor types, prostate cancer and COVID-19 share several risk factors, and the interaction of prostate cancer and COVID-19 is purported to have an adverse outcome. METHODS: This was a single-institution retrospective study on 286,609 patients who underwent the COVID-19 test at Mount Sinai Hospital system from March 2020 to December 2020. Chi-square/Fisher's exact tests were used to summarize baseline characteristics of categorical data, and Mann-Whitney U test was used for continuous variables. Univariable logistic regression analysis to compare the hospitalization and mortality rates and the strength of association was obtained by the odds ratio and confidence interval. RESULTS: This study aimed to compare hospitalization and mortality rates between men with COVID-19 and prostate cancer and those who were COVID-19-positive with non-prostate genitourinary malignancy or any solid cancer, and with breast cancer patients. We also compared our studies to others that reported the incidence and severity of COVID-19 in prostate cancer patients. Our studies highlight that patients with prostate cancer had higher susceptibility to COVID-19-related pathogenesis, resulting in higher mortality and hospitalization rates. Hospitalization and mortality rates were higher in prostate cancer patients with COVID-19 when compared with COVID-19 patients with non-prostate genitourinary (GU) malignancies.

Management of patients who opt for radical prostatectomy during the coronavirus disease 2019 (COVID-19) pandemic: an international accelerated consensus statement.

OBJECTIVE: Coronavirus disease-19 (COVID-19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non-metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID-19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic. METHODS: We conducted an accelerated consensus process and systematic review of the evidence on COVID-19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways. RESULTS: Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID-19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID-19 were coined as 'COVID-19 cold' sites. CONCLUSION: Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3-6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID-19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery.

Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.

PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol.

Social Determinants Predict Outcomes in Data From a Multi-Ethnic Cohort of 20,899 Patients Investigated for COVID-19.

Importance: The COVID-19 pandemic exploits existing inequalities in social determinants of health (SDOH) in disease burden and access to healthcare. Few studies have examined these emerging disparities using indicators of SDOH. Objective: To evaluate predictors of COVID-19 test positivity, morbidity, and mortality and their implications for inequalities in SDOH and for future policies and health care improvements. Design, Setting, and Participants: A cross sectional analysis was performed on all patients tested for COVID-19 on the basis of symptoms with either a history of travel to at risk regions or close contact with a confirmed case, across the Mount Sinai Health System (MSHS) up until April 26th 2020. Main Outcomes and Measures: Primary outcome was death from COVID-19 and secondary outcomes were test positivity, and morbidity (e.g., hospitalization and intubation caused by COVID-19). Results: Of 20,899 tested patients, 8,928 tested positive, 1,701 were hospitalized, 684 were intubated, and 1,179 died from COVID-19. Age, sex, race/ethnicity, New York City borough (derived from first 3 digits of zip-code), and English as preferred language were significant predictors of test positivity, hospitalization, intubation and COVID-19 mortality following multivariable logistic regression analyses. Conclusions and Relevance: People residing in poorer boroughs were more likely to be burdened by and die from COVID-19. Our results highlight the importance of integrating comprehensive SDOH data into healthcare efforts with at-risk patient populations.

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients.

Coronavirus disease-2019 (COVID-19), a disease caused by Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages in the United States, and the highest incidence and mortality in adult men. As the pandemic evolves there is limited understanding of a potential association between symptomatic viral infection and age. To date, there is no knowledge of the role children (prepubescent, ages 9-13 years) play as "silent" vectors of the virus, with themselves being asymptomatic. Throughout different time frames and geographic locations, the current evidence on COVID-19 suggests that children are becoming infected at a significantly lower rate than other age groups-as low as 1%. Androgens upregulate the protease TMPRSS2 (type II transmembrane serine protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. Owing to low levels of steroid hormones, prepubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells. As the world anticipates a vaccine against SARS-CoV-2, the role of prepubescent children as vectors transmitting the virus must be interrogated to prepare for a potential resurgence of COVID-19. This review discusses the current evidence on the low incidence of COVID-19 in children and the effect of sex-steroid hormones on SARS-CoV-2 viral infection and clinical outcomes of pediatric patients. On reopening society at large, schools will need to implement heightened health protocols with the knowledge that children as the "silent" viral transmitters can significantly affect the adult populations.

Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer.

The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.

Urologic oncology practice during COVID-19 pandemic: A systematic review on what can be deferrable vs. nondeferrable.

PURPOSE: To provide a review of high-risk urologic cancers and the feasibility of delaying surgery without impacting oncologic or mortality outcomes. MATERIALS AND METHODS: A thorough literature review was performed using PubMed and Google Scholar to identify articles pertaining to surgical delay and genitourinary oncology. We reviewed all relevant articles pertaining to kidney, upper tract urothelial cell, bladder, prostate, penile, and testicular cancer in regard to diagnostic, surgical, or treatment delay. RESULTS: The majority of urologic cancers rely on surgery as primary treatment. Treatment of unfavorable intermediate or high-risk prostate cancer, can likely be delayed for 3 to 6 months without affecting oncologic outcomes. Muscle-invasive bladder cancer and testicular cancer can be treated initially with chemotherapy. Surgical management of T3 renal masses, high-grade upper tract urothelial carcinoma, and penile cancer should not be delayed. CONCLUSION: The majority of urologic oncologic surgeries can be safely deferred without impacting long-term cancer specific or overall survival. Notable exceptions are muscle-invasive bladder cancer, high-grade upper tract urothelial cell, large renal masses, testicular and penile cancer. Joint decision making among providers and patients should be encouraged. Clinicians must manage emotional anxiety and stress when decisions around treatment delays are necessary as a result of a pandemic.