Closing Gaps in Care: COVID-19 in Patients With Cancer Bring Health Inequities to the Surface

According to the CDC, patients at any age who have cancer are at an increased risk of severe illness due to coronavirus disease 2019 (COVID-19), and this may be aggravated by aspects such as race, ethnicity, and socioeconomic factors.¹ Discrepancies in patient outcomes were explored in a virtual symposium on health inequities in the COVID-19 pandemic at the COVID-19 and Cancer meeting, hosted by the American Association for Cancer Research.

The United States has the highest number of reported cases of COVID-19 cases in the world, with deaths occurring more often in patients with advanced age and comorbidities. The disparity for COVID-19 deaths is seen for all age groups, with African Americans showing the highest death rates at any age. Compared with non-Hispanic whites, both African American and Hispanic COVID-19 deaths outpace those of non-Hispanic whites, even at younger ages.

“In my own state of Michigan, African Americans’ share of cases, as well as deaths, greatly outstrip the proportion of African Americans in the state population,” John M. Carethers, MD, professor and chair of the Department of Internal Medicine and professor of human genetics at the University of Michigan Medical School in Ann Arbor, said during his presentation.² “Overall, African Americans make up 13% of the population but make up 23% of COVID-19 deaths. If you assess this per 100,000 population, [deaths in] non-Hispanic whites occur at a rate of 27 per 100,000, [whereas] African Americans are at a whopping 62 per 100,000.”

In one cross-sectional study evaluating the association between COVID-19 infection and mortality rate from 369 counties of 7 states, African Americans were observed to be more vulnerable to the virus than any other ethnic group. Variables irrespective of race that were most closely associated with death rates in the study were medical disabilities, lack of grocery mobility, and poverty.³

In a cohort of patients hospitalized with laboratory-confirmed COVID-19, cancer status, race and ethnicity, and descriptive statistics for baseline characteristics were collected to analyze the cumulative effects in patient mortality.

The findings showed that patients in the COVID-19–positive cancer population were more likely to be African American, present at an older age, and have an increased risk of intensive care stay and intubation, as well as a longer duration of hospital and intensive care time, compared with the COVID-19–positive population without cancer. There was a trend toward higher rates of death in African Americans, men, and patients on Medicare/Medicaid in the COVID-19–positive cancer population, but those associations were not found to be statistically significant.⁴

“There was a disproportionate number of men and specifically, African American men, who were coming in and requiring hospitalization,” Steven S. Chang, MD, director of the Head and Neck Cancer Program at the Henry Ford Cancer Institute in Detroit, Michigan, said while presenting the data. “Once they are in the hospital, their outcomes were similar regardless of race, but the factors that led to the emergency room door were probably the drivers of morbidity.”

Can Baseline Biological Factors Explain COVID-19 Outcomes?

It has been surmised that higher mortality and infection rates among racial minorities may be due to disproportionally increased non–COVID-19 comorbidities seen in stratified patient subgroups.

“African Americans in particular carry more health conditions making them more susceptible to COVID-19, with a higher vulnerability index in the middle and older ages and higher numbers of comorbid risk factors…compared with non-Hispanic whites,” Carethers said.

However, recent studies suggest that this may not represent the full scope of the issue. In one study, the risk of testing positive for the virus by race and ethnicity compared with the non-Hispanic white population carried higher odds ratios (ORs) in patients who identified as Hispanic/Latino (age-adjusted OR, 2.69; 95% CI, 2.14-3.39), African American (age-adjusted OR, 3.69; 95% CI, 2.83-4.81), and Asian (age-adjusted OR, 1.87; 95% CI, 1.36-2.58). When adjusted for sex, history of diabetes, heart disease, lung disease, kidney disease, current smoker status, and body mass index, corresponding ORs in the same patient subgroups did not change drastically (multivariate OR, Hispanic/Latino [2.68; 95% CI, 2.13-3.38], African American [3.51; 95% CI, 2.68-4.60], and Asian [1.97; 95% CI, 1.43-2.73]).⁵

Hydroxychloroquine, a drug used to prevent and treat COVID-19 in the early days of the pandemic, was since found to offer no benefit to infected patients.⁶ In patients who have a sodium channel variant known as p.Ser1103Tyr-SCN5A, seen in 1 in 13 African Americans, there is a higher risk of heart arrythmia and sudden cardiac death, which can be exacerbated by COVID-19–related conditions such as hypoxia, myocardial injury, cytokine storm, and use of QTc-prolonging drugs.⁷

“The coalescing of these 3 items puts the patient at extremely high risk for sudden cardiac death,” said Carethers, although he noted that there aren’t any study findings to confirm this association.

Sexual dimorphic responses to COVID-19 may be due to expression of the receptor ACE2 and serine protease TMPRSS2 for S protein priming, which both are necessary cellular factors for virus entry to human cells.⁸ Preexisting conditions may explain why these have upregulated expression in certain patients. In patients with asthma, those who were men, African American, and/or had diabetes all had increased ACE2 and/or TMPRSS2 from collected sputum cells, providing rationale for monitoring these subgroups for COVID-19 outcomes.⁹ Patients with lung diseases, including cancer, also have increased expression of TMPRSS2.¹⁰

Impact of Socioeconomic Factors

Carethers also pointed out that a societal picture could provide the greatest rationale for disparities in infection rates and outcomes in patients infected with COVID-19

“It starts with socioeconomic inequality, where you have lower status, lower level of education, and difficult access to health care that causes downstream consequences [FIGURE],” Carethers said.^2,11 “This in turn causes changes to physiology, which include alterations to the lung and gut microbiome, increased localized inflammation, and compromised immunity. That affects the pathophysiologic health morbidities of cancer, obesity, diabetes, COPD [chronic obstructive pulmonary disorder] and asthma, hypertension, and cardiovascular and chronic kidney disease.”

The high unemployment rate, in large part caused by the pandemic, worsens inequities in health care. According to the Bureau of Labor and Statistics, the rate of unemployment in May was at 13.3, the highest since level since the Great Depression. Importantly, job loss for many patients also leads to loss of medical insurance and in turn reduces access to cancer screening.

In one study that used data from the National Health Interview Survey, the relationship between unemployment, health insurance status, and cancer screening was examined to inform the potential lasting effects of COVID-19. Forty percent of patients who were unemployed were also uninsured versus roughly 10% of those who were currently working, with unemployed individuals more likely to have Medicaid. Racial minority groups were also more likely to be unemployed than employed, including Hispanic and African American respondents.¹²

Controlling for nonmodifiable risk factors, unemployed individuals were less likely to be up-to-date on breast and colorectal cancer screenings, leading the investigators to conclude that unemployment is adversely associated with guideline-recommended care.

“This is concerning because we know that cancer screening can potentially save lives,” Stacey A. Fedewa, PhD, an epidemiologist and senior principal scientist in the Surveillance and Health Services Research Program at the American Cancer Society, said while presenting the study data. “Because a growing number of people are losing their jobs and several racial and ethnic minority groups are more likely to be unemployed, this could drive disparities even further than what is seen now.”

Carethers concluded by reflecting on how socioeconomic and biological factors together explain why these differences in outcome may exist. “In many ways, the disparities observed with COVID-19 may start from socioeconomic vulnerabilities that enter a vicious cycle of comorbidities, increased ACE2 and TMPRESS2 expression that [boosts] one’s susceptibility to COVID-19, and lead to severe illness and death,” he said. “If one survives, they become more vulnerable from the aftereffects of COVID-19 and more socioeconomically disadvantaged with loss of jobs.”

Although Carethers acknowledged that there is no quick fix for these issues, he is optimistic that bringing these data to the surface will help undermine some of the structural issues that are responsible for aggravating health disparities. “COVID-19 has enhanced the visibility of some of the [structural inequalities] that we have in the United States, and most people are seeing that,” he said.

This is the first article in a series related to health disparities and their effects on patients with cancer. In the next issue, inequities seen in conducting clinical trials will be reviewed.

_References:

_{1. People with certain medical conditions. CDC. Updated July 17, 2020. Accessed July 23, 2020. https://bit.ly/2WOVvN0}

_{2. Carethers JM. Potential insights into COVID-19 disparities from the science of cancer health disparities. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.}

_{3. Abedi V, Olulana O, Avula V, et al. Racial, economic and health inequality and COVID-19 infection in the United States. medRxiv. Published online May 1, 2020. doi:10.1101/2020.04.26.20079756}

_{4. Chang SS, Hwang C, Elshaikh MA, et al. Outcomes by race for cancer patients hospitalized with SARS-CoV-2 infection. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.}

_{5. Lo CH, Nguyen LH, Drew DA, et al. Racial and ethnic determinants of Covid-19 risk. medRxiv. Published online June 20, 2020. doi:10.1101/2020.06.18.20134742 6. Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;382(25):24112418. doi:10.1056/NEJMoa2012410}

_{7. Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ. Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans. Heart Rhythm. Published online May 5, 2020. doi:10.1016/j. hrthm.2020.04.045}

_{8. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. doi:10.1016/j. cell.2020.02.052}

_{9. Peters MC, Sajuthi S, Deford P, et al. COVID-19-related genes in sputum cells in asthma. relationship to demographic features and corticosteroids. Am J Respir Crit Care Med. 2020;202(1):83-90. doi:10.1164/ rccm.202003-0821OC}

_{10. Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. medRxiv. Published online March 27, 2020. doi:10.1101/2020.03.21.20040261}

_{11. Carethers JM, Doubeni CA. Causes of socioeconomic disparities in colorectal cancer and intervention framework and strategies. Gastroenterology. 2020;158(2):354-367. doi:10.1053/j.gastro.2019.10.029}

_{12. Fedewa SA, Yabroff KR, Zheng Z, et al. Unemployment and cancer screening: baseline estimates to inform healthcare provision in the context of COVID-19 economic distress. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.}