Quantifying mortality burden in patients with cancer due to COVID‐19 in the US: A national cross‐sectional analysis

Abstract Introduction There is limited information on the impact of certain social factors on mortality outcomes in patients with cancer and COVID‐19 on a national scale. This study aims to characterize excess mortality and analyze a subset of sociodemographic trends in COVID‐19 and cancer mortality. Methods Patients with cancer listed on their death certificates from 2018 to 2021 and patients with COVID‐19 and cancer listed on multiple cause of death certificates from the CDC Wide‐Ranging Online Data for Epidemiologic Research database from March 2020 to December 2021 were included. Age‐adjusted mortality rates (AAMR) per 1,000,000 population were compared across race/ethnicity groups, sex, and census regions. Crude mortality rates were compared across different age groups and regions based on urbanization status. Results Average AAMR in patients with COVID‐19 and cancer was 41.7 in 2020 and 56.7 in 2021. Conclusions Mortality rates in patients with cancer and COVID‐19 were significantly higher in certain populations. Targeted interventions are necessary to improve outcomes.

race/ethnicity, age greater than or equal to 85, and residence in a large central metropolitan area were significant risk factors for mortality in patients with cancer and COVID-19. 6This study aims to expand upon this data by (1) characterizing excess mortality due to COVID-19 compared to prepandemic levels using data from 2018 to 2021 and (2) analyzing sociodemographic trends, particularly in race/ethnicity groups, sex, census regions, urbanization status, and age groups, in mortality rates in patients with COVID-19 and cancer with newly available 2021 data to assess the effect of widespread vaccine availability on this relationship.

| METHODS
The Multiple Cause of Death (MCOD) CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database was queried for de-identified data on patients with malignant neoplasms (ICD-10 C00-C97) listed on their death certificates from 2018 to 2021, and COVID-19 (ICD-10 *U07.1) and cancer listed from March 2020 to December 2021. 7Excess mortality was calculated by comparing the increase in total deaths from the prepandemic (March 2018-December 2019) to pandemic period (March 2020-December 2021).Yearly age-adjusted mortality rates (AAMR) per 1,000,000 population and average monthly deaths during the prevaccination (March 2020-January 2021) and vaccination (February 2021-December 2021) periods were compared across race/ethnicity groups, sex, and census regions using 95% confidence intervals (CI).Crude mortality rates were compared across various age groups and regions based on urbanization status.Descriptive statistics were used to evaluate the results.Race/ethnicity groups and the different age groups are shown in Table 1.Urbanization status and nine census divisions were included based on the 2013 NCHS Urban-Rural Classification Scheme for Counties and the U.S. Census Bureau, respectively. 8,9As CDC WONDER Data is de-identified and publicly available, this study was deemed exempt from IRB review.

| Overall changes during the pandemic
Total deaths in patients with cancer during the pandemic was 1,266,958 which was increased by 4.1%, or 50,264 excess deaths, compared to pre-pandemic totals.Deaths in patients with both COVID-19 and cancer listed on MCOD during the pandemic totaled 40,702, or 81.0% of the excess death total in patients with cancer during the pandemic.Yearly totals were 17,392 and 23,310 in 2020 and 2021 respectively.Monthly average deaths decreased by 18.5% in the period of vaccination availability compared to the prevaccination period.(Figure 1).

| AAMR comparisons
AAMR in patients with COVID-19 and cancer on MCOD was 41.7 (95% CI: 41.0-42.3) in 2020 and 56.7 (95% CI: 56.0-57.5) in 2021, an increase of 36%.AAMR was significantly higher in NH American Indian or Alaskan Native, NH Black or African American, and Hispanic or Latino race/ethnicity groups compared to NH White and NH Asian race/ethnicity groups in 2020.In 2021, NH Asian race/ethnicity group had significantly lower AAMR than all other race/ethnicity groups through the course of the pandemic.AAMR was significantly higher in males across both years.(Table 1).
Annual percentage change (APC) in AAMR from 2020 to 2021 for male and female sex increased by 32.2% and 40.6%, respectively.Regarding race/ethnicity groups, NH White had the only significant increase in APC in AAMR of 46.6%.East South Central, Mountain, and Pacific regions had the highest significant increases in APC.(Table 1).

| Crude mortality rate comparisons
Regarding urbanization status, rural counties had significantly higher crude mortality rates across both years and the largest increase in APC.Death rates increased with age, and ages 85 years or greater was associated with the highest crude mortality rates across both years.Ages 25-34 years had the largest increase in APC.(Table 1).

| DISCUSSION
In this study, we found mortality in patients with cancer increased by approximately 4%, over 50,000 excess deaths, during the COVID-19 pandemic.Patients with COVID-19 and cancer as contributing causes of death accounted for approximately 80%, or 40,000 of these deaths.AAMR in patients with cancer and COVID-19 were found to be significantly higher in NH Black or African American, Hispanic or Latino, and NH American Indian or Alaskan Native groups in 2020, exacerbating persistent disparities in health outcomes in these groups in the US.This goes in line with known findings which showed that cancer-associated COVID-19 mortality was higher in Black and Hispanic groups compared to NH White and NH Asian groups. 3 White had the only significant increases in AAMR in 2021, despite the widespread availability of vaccines, which merits further investigation.AAMR was also significantly higher in males compared to females.This finding correlates with prior research which has shown the risk of mortality in COVID-19 patients is higher in males compared to females.Cancer patients are also more likely to be male, a significant predictive factor for COVID-19 mortality. 10Males have a slightly higher chance of being diagnosed with an invasive cancer in their lifetime compared to females which may be due to various behavioral, biological, and environmental factors. 11Crude mortality rates were highest in rural areas, and this disparity only furthered during 2021.AAMR in those 85 and older was highest, but the greatest increase in mortality from 2020 to 2021 was experienced by those ages 45-64.
Limitations included that we did not utilize underlying cause of death to provide broader comparison across groups.Since the study only utilized MCOD data, it may be difficult to ascertain whether the underlying cause of death is from COVID-19, cancer, or another underlying condition that worsened the state of either of the two medical conditions.The study also primarily focused on patients with cancer in general and did not investigate trends in specific cancers, stages, subtypes, and treatments.This is important to acknowledge as certain cancers and stages of cancer, such as lung cancer, may have a more aggressive course and be associated with higher rates of mortality whereas other types may have a more indolent course and may be incidentally detected through screening, such as certain grades of prostate cancer. 11Such research has previously been explored in brief but merits further detailed investigation as a direction for future research once national data becomes available.Furthermore, AAMR in 2020 may be lower because COVID-19 did not become widespread until March 2020, which must be considered when using this comparison; however, this method allows for identification of significant differences across groups.
This study found that rates were higher in minority groups, especially in 2020, but NH White patients had a significant increase in 2021 despite widespread vaccination availability.Identification of patients with cancer at higher risk of death from COVID-19 is important to address disparities in access or care (e.g., vaccination uptake) due to structural racism and other socioeconomic causes to prevent adverse outcomes including mortality.Cancer patients are at an increased risk of developing post-COVID-19 complications that may affect various organs; those especially at risk include male gender and patients 65 years and older. 12THOR CONTRIBUTIONS Bhaghyasree Jambunathan: Conceptualization (lead); investigation (equal); methodology (equal); project administration (equal); writing -original draft (lead); writing -review and editing (equal).Jacob Lang: Conceptualization (equal); formal analysis (lead); investigation (equal); methodology (equal); visualization (lead); writing -original draft (equal); writing -review and editing (equal).Malik Mays: Conceptualization (equal); investigation (equal); writing -original draft (equal); writing -review and editing (equal).Obi Ekwenna: Conceptualization (equal); investigation (equal); methodology (equal); project administration (equal); supervision

F I G U R E 1
Monthly death totals for patients with COVID-19 and cancer listed on MCOD from March 2020 to December 2021.

Urbanization status Crude mortality rate (95% CI) Crude mortality rate (95% CI)
Total deaths, mortality rates, and percentage change across variable sociodemographic groups in 2020 and 2021.
T A B L E 1