Role of race in accelerating progression of colorectal cancer

African Americans present earlier in age and have higher incidence and mortality from colorectal cancer (CRC) compared to Whites. Socioeconomic inequality in the US that leads to higher comorbid illness among African Americans is likely a driver. Subsequent biological differences in African Americans include higher risk adenoma precursors that are more often proximally located in the colon, low microstatellite instability prevalence, and deficient immunologic profiles compared to Whites that contribute to cancer progression and outcome. Screening for CRC among African Americans had been recommended by some organizations to commence at age 45 or 40 years due to the observed epidemiology;this was not implemented until the US Preventive Services Task Force recommended CRC screening to commence at age 45 years for all races and ethnicities in 2021.Screening for CRC is one modality of intervention that can eliminate disparities;both colonoscopic and non-invasive screening have been shown to eliminate incidence and mortality differences between African Americans and Whites when using navigation. Recent gains in screening utilization among African Americans compared to Whites might be erased as a result of the COVID-19 pandemic. Navigated non-invasive CRC screening might help the unevenness of preventive services recovery from the pandemic if it can be fully implemented.

DIARRHEA, ELEVATED AST, AND ELEVATION OF INFLAMMATORYRELATED BIOMARKERS IS A PREDICTOR FOR MORTALITY IN MINORITY HOSPITALISED COVID-19 PATIENTS

Background and Aims: Initial reports on US COVID-19 showed different outcomes in different races. In this study, we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. Methods: We analyzed data from hospitalized COVID- 19 patients (n=5,852) from 8 hospitals. Demographics, comorbidities, symptoms and laboratory data were collected. Results: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and dead patients' mean ages were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, and EA were 14.8%, 7.3%, and 16.3%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation, respiratory failure, shortness of breath (SOB) (p<0.01), fatigue (p=0.04), diarrhea (p=0.02), and increased AST (p<0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had a higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables were age (over 45 years old), male sex, EA, patients hospitalized in Indiana, Michigan, Georgia, and District of Columbia. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP, and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID- 19 death in our cohort. Conclusion: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, predictors of mortality include male gender, diarrhea, elevated AST, comorbidities, respiratory symptoms and failure, and elevation of inflammatory- related biomarkers. These findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to a high frequency of comorbidities and older age among AA.

Potential insights into COVID-19 disparitiesfrom the science of cancer health disparities

Older age as well as health comorbidities that include metabolic syndrome, cardiovascular disease, hypertension, asthma, and chronic kidney disease are listed by the Centers for Diseases Control and Prevention (CDC) as strongrisk factors for severe disease and mortality from COVID-19. Since the outbreak began throughout the world and theUnited States, both gender and race/ethnicity have additionally become associated with infection and severeCOVID-10 disease and mortality. While all humans lacked immunity at its onset to the new SARS-CoV-2 virus, thecause of COVID-19, older-age individuals are likely more susceptible due to age-weakened immune systems, thepresence of health comorbidities, and are the most likely group to be housed within skilled nursing facilities (SNFs)where outbreaks and death from COVID-19 have been frequent. SNFs often lacked isolation protocols, initial viraltesting, and lacked personalized protection equipment (PPE) that was prioritized to hospitals. People with healthcomorbidities regardless of age are more susceptible to severe COVID-19 likely because of weakened health andimmunity. Indeed, patients on immunosuppression for medical conditions were among the first susceptible to severeinfection when the outbreak began. The association of severe COVID-19 and race/ethnicity shows the strongestrationale with socioeconomic inequalities. Those from minority-population backgrounds are often in more urbancrowded areas where mitigating factors of social distancing and opportunities to avoid virus exposure are lessrealized. Many minority populations, as a result of socioeconomic inequality, have more difficult access to healthcare, hold lower-paying jobs, reside in lower-income neighborhoods with grocery store deserts, have higher use oftobacco and alcohol and demonstrate lower physical activity, and have lower use of preventive medicine. This inturn has the physiologic consequences of alteration of the gut microbiome, increased localized inflammation, andcompromised immunity, leading to higher frequencies of health comorbidities, the exact conditions that have beenshown to place an individual at much higher risk for mortality from COVID-19. Other COVID-19 risk factors such asblood group type A and the use of angiotensin-converting enzyme (ACE) inhibitors for the high prevalence ofessential hypertension and cardiovascular disease in racial populations appear not to play a role. Specific spikeprotein variants that have proved to be more virulent have not been evaluated among racial groups. The use ofhydroxychloroquine might play a role in sudden death if used for treatment or prophylaxis of COVID-19 in someAfrican Americans because of the common presence of a cardiac sodium channel polymorphism. The higher risk formen over women for severe COVID-19 disease is intriguing;the SARS-CoV-2 virus requires the use of cell ACE2receptors and the cell serine protease TMPRSS2, both regulated by androgens for expression. Differences inexpression levels as well as trials of antiandrogen therapy are both being explored to assess if these permissive cellfactors are the cause for gender differences.

Insights into disparities observed with COVID-19.

The onset of human disease by infection with SARS-CoV-2 causing COVID-19 has revealed risk factors for disease severity. There are four identified factors that put one at high risk for infection and/or mortality creating a disparity: age, co-morbidities, race/ethnicity and gender. Data indicate that the older a person is, and/or the presence of obesity and diabetes, cardiovascular disease and chronic kidney disease place one at higher risk for COVID-19. In the United States, specific race/ethnicities, particularly African Americans and Native Americans, are strong COVID-19 risk components. Male gender has also emerged as a severity risk factor. For age and racial/ethnicities, the accumulation of health co-morbidities is common precipitating mechanisms. In particular, underlying socio-economic structures in the United States likely drive development of co-morbidities, putting affected populations at higher risk for severe COVID-19. Sudden cardiac death triggered by a common sodium channel variant in African Americans with COVID-19 has not been evaluated as a cause for racial disparity. There is no evidence that racial/ethnic differences for COVID-19 are caused by ABO blood groups, use of angiotensin-converting enzyme (ACE) inhibitors or from amino acid substitutions in the SARS-CoV-2 spike protein. There is growing evidence that androgen-enabled expression of ACE2 receptors and the serine protease TMPRSS2, two permissive elements engaging the SARS-CoV-2 spike protein for infection, may contribute to severe COVID-19 in men. Overall, COVID-19 has generated disparities for who is infected and the severity of that infection. Understanding the mechanisms for the disparity will help nullify the differences in risk for COVID-19.