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. 2021 Jul 21;16(7):e0254809. doi: 10.1371/journal.pone.0254809

The impact of race and ethnicity on outcomes in 19,584 adults hospitalized with COVID-19

Ann M Navar 1,*, Stacey N Purinton 2, Qingjiang Hou 2, Robert J Taylor 2, Eric D Peterson 1
Editor: Stanislaw Stepkowski3
PMCID: PMC8294547  PMID: 34288941

Abstract

Introduction

At the population level, Black and Hispanic adults in the United States have increased risk of dying from COVID-19, yet whether race and ethnicity impact on risk of mortality among those hospitalized for COVID-19 is unclear.

Methods

Retrospective cohort study using data on adults hospitalized with COVID-19 from the electronic health record from 52 health systems across the United States contributing data to Cerner Real World DataTM. In-hospital mortality was evaluated by race first in unadjusted analysis then sequentially adjusting for demographics and clinical characteristics using logistic regression.

Results

Through August 2020, 19,584 patients with median age 52 years were hospitalized with COVID-19, including n = 4,215 (21.5%) Black and n = 5,761 (29.4%) Hispanic patients. Relative to white patients, crude mortality was slightly higher in Black adults [22.7% vs 20.8%, unadjusted OR 1.12 (95% CI 1.02–1.22)]. Mortality remained higher among Black adults after adjusting for demographic factors including age, sex, date, region, and insurance status (OR 1.13, 95% CI 1.01–1.27), but not after including comorbidities and body mass index (OR 1.07, 95% CI 0.93–1.23). Compared with non-Hispanic patients, Hispanic patients had lower mortality both in unadjusted and adjusted models [mortality 12.7 vs 25.0%, unadjusted OR 0.44(95% CI 0.40–0.48), fully adjusted OR 0.71 (95% CI 0.59–0.86)].

Discussion

In this large, multicenter, EHR-based analysis, Black adults hospitalized with COVID-19 had higher observed mortality than white patients due to a higher burden of comorbidities in Black adults. In contrast, Hispanic ethnicity was associated with lower mortality, even in fully adjusted models.

Introduction

The COVID-19 pandemic caused approximately 375,000 deaths in the United States in 2020, and was either the cause of death or contributing cause of death for 11.3% of all deaths in the United States [1]. Likely due to COVID-19, the age-adjusted mortality increased in the United States by 15.9% in 2020 [2]. Among patients hospitalized for COVID-19, the mortality rate has generally decreased over time, but has been shown to vary across hospitals, with one study showing a 50% variability in risk-standardized event rates of mortality or referral to hospice among COVID-19 patients in the first six months of the pandemic [3].

COVID-19 has also had a disproportionate impact on Black and Hispanic populations [4, 5]. Specifically, Black and Hispanic adults in the United States are at increased risk of severe infection and are nearly 3 times more likely to die of COVID-19 compared with non-Hispanic white person [6]. It has been less clear, however, whether Black and Hispanic patients hospitalized with COVID-19 have higher mortality. To date, reports on the impact of race and ethnicity on mortality in patients hospitalized with COVID-19 have come from either single center databases, specialized populations such as the Veterans Affairs hospital, or from selected centers participating in a prospective registry [711]. Accurate information regarding the impact of race and ethnicity on outcomes is important to help physicians identify higher risk patients when admitted, to identify potential biological mechanisms affecting prognosis, and to target public health interventions appropriately. Most importantly, differences in outcomes by race and ethnicity may serve as an indicator of systemic biases in the healthcare system, with differential treatment leading to differential outcomes.

National data from electronic health records (EHR) from community hospitals offer the ability to evaluate risk factors for complications of COVID-19 and mortality. In 2020, Cerner Corporation, partnered with Amazon Web Services to create a national EHR-based deidentified dataset of all patient hospitalized with COVID-19 who participate in Cerner Real World DataTM.

Using this dataset, we sought to evaluate race and ethnic differences in patients hospitalized for COVID-19 from across the United States, and the impact of race and ethnicity on mortality.

Methods

This study was deemed exempt from human subjects review as it used de-identified data by the Duke University Institutional Review Board (Pro00105396). Data from Cerner’s COVID-19 database derived from Cerner Real World DataTM were used to identify patients hospitalized with COVID-19. The dataset for this analysis was created in August 2020 using data through August 3, 2020. In order to de-identify the data, all dates are shifted up to 8 weeks for each patient, therefore the shifted dates in the study dataset (as opposed to the actual dates of the hospitalizations) ranged from December 1, 2019 through September 2, 2020. For this analysis, we identified all patients age 18 or older who were hospitalized with COVID-19, including those with a positive lab test for SARS-CoV-2 during or within 2 weeks of the hospitalization, as well as patients hospitalized with a diagnosis consistent with COVID-19 disease (S1 Table). Laboratory tests assessed included antigen-based tests; antibody tests were not used. Patients with positive laboratory tests for other coronaviruses than SARS-CoV-2 were also excluded. Only one hospitalization per patient was used; for patients with multiple hospitalizations the most recent hospitalization was considered. For patients admitted from the emergency room, emergency room visit information was combined with the inpatient admission to create a single episode of care.

Demographic data available on the study sample patients included age, sex, race, insurance status, ethnicity, and first digit of ZIP code. For some patients, race and ethnicity data were reported multiple times across different encounters. To determine race and ethnicity, we evaluated for the presence of an indicator of race within 3 years of and including the analysis hospitalization. For patients with different races listed across different encounters, the patient’s race was set to “multiple races.” Geographic location for patients included first digit of zip code for the patient. Encounter information for the study COVID-19 hospitalization included admission and discharge dates (shifted within patient to de-identify as above), medications administered, procedures, diagnoses, and laboratory data.

Patient comorbidities at the time of hospital admission, were defined using international classification of disease, version 10 (ICD-10) diagnosis codes, MEDCIN codes, and SNOMED codes recorded during previous inpatient and outpatient encounters in the same healthcare system in the past 3 years. Patients without any encounters in the Cerner electronic health record prior to hospitalization were excluded from models that included comorbidities. Obesity was defined using the body mass index (BMI) or weight and height measurements taken during the hospital visit, or if not available, then the most recent body mass index measurement prior to the index admission was used, with a cutoff for obesity of > 30.0 kg/m2.

Clinical complications of COVID-19 were identified using diagnosis and procedure codes from the hospitalization. Mortality was assessed among patients either discharged alive or who died during the index stay. Patients transferred to other facilities, those discharged to hospice, and those still admitted at the time of dataset creation were excluded from the analysis.

Descriptive statistics are presented for characteristics and outcomes for patients hospitalized COVID-19 by race and ethnicity, with t-tests used for continuous variables and Pearson Chi-squared tests or Fisher’s exact tests used for categorical variables when applicable.

To evaluate the impact of race and ethnicity on the risk of mortality, univariable logistic regression was first used to evaluate the association between sex, race, ethnicity, insurance, geographic region, age, and calendar date of admission. Age and date of admission were modeled using a restricted cubic spline (RCS) function to account for their non-linear effect with knots selected at 5 (5, 27.5, 50, 72.5, 95) and 3 (27.5, 50, 72.5) percentile points, and then considered as such for inclusion in the multivariable model, respectively. Multivariable logistic regression was then performed to evaluate the association between nonclinical factors and the in-hospital mortality including age, sex, race, ethnicity, insurance category, geographic region, and time of hospital admission. Patients with sex as either missing or “other” were excluded from the multivariable analysis given small overall numbers (n = 47). Patients with missing data for race, ethnicity, insurance status, or ZIP code were not excluded; these variables were modeled as “missing”. Reference categories for race and ethnicity were white and non-Hispanic, respectively.

Next, a multivariable model was created to evaluate the association between race and ethnicity and outcomes further adjusting for patient comorbidities including asthma, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, end stage renal disease, heart failure, hypertension, and BMI. This analysis only included those who had at least one prior visit in the dataset to determine prior comorbidities and those for whom BMI data were available. BMI was modeled with RCS function with knots selected at 3 (27.5, 50, 72.5) percentile points to account for nonlinearity. All demographic, race, and ethnicity variables were included in the model, with stepwise variable selection used for clinical variables with a retention p-value of <0.05.

Results

Cohort characteristics and unadjusted outcomes

We identified 28,299 patients hospitalized with COVID-19 during the analytic window. At the time the dataset was created, n = 1729 (6.1%) were still hospitalized, n = 466 (1.6%) had been discharged to hospice, n = 4689 (16.6%) were transferred to another facility, and discharge status was unknown for n = 1,831 (6.5%). The breakdown of those with unknown discharge status is presented in S2 Table; Black patients had the highest rates of unknown discharge status while white patients had highest rates of transfers. This left a total of 19,584 patients for whom discharge disposition was available. Race data was missing for n = 1,017 (5.19%) of patients overall.

Differences in hospitalized cases by race and ethnicity

Overall, 51.0% (n = 9994) of our sample was white while 21.5% were recorded as Black (n = 4215). Table 1 shows differences between Black and white adults admitted with COVID-19. Black adults were younger (median age 59 vs 62 years), less likely to be male (47.3% vs 53.0%), less likely to be Hispanic (1.9% vs 36.3%), had higher BMIs (median BMI 30.7 vs 38.9), and different distribution of insurance coverage (p<0.001 for all). Black patients also had higher rates of diabetes, hypertension, coronary artery disease, heart failure, chronic kidney disease, and end stage renal disease, and lower rates of COPD and asthma (see Table 1).

Table 1. Characteristics of white, Black, Hispanic, and non-Hispanic patients hospitalized with COVID-19.

White N = 9994 Black N = 4215 Hispanic N = 5761 Non-Hispanic N = 11,269
Age
    Median (IQR) 62 (49, 76) 59 (47, 71) 62 (49, 76) 59 (47, 71)
    18–39 1,432 (14.33) 671 (15.92) 1,198 (20.8) 1,499 (13.3)
    40–49 1,137 (11.38) 556 (13.19) 937 (16.26) 1,227 (10.89)
    50–59 1,846 (18.47) 903 (21.42) 1,236 (21.45) 2,126 (18.87)
    60–69 1,974 (19.75) 919 (21.8) 1,049 (18.21) 2,430 (21.56)
    70–79 1,737 (17.38) 710 (16.84) 684 (11.87) 2,054 (18.23)
    80–89 1,863 (18.64) 453 (10.75) 652 (11.32) 1,927 (17.10)
    ≥90 5 (0.05) 3 (0.07) 5 (0.09) 6 (0.05)
Sex
    Male 5,297 (53.00) 1,994 (47.31) 3,045 (52.86) 5,758 (51.10)
Race
American Indian or Alaska 23 (0.40) 438 (3.89)
Asian or Pacific islander 24 (0.42) 626 (5.56)
Black or African American 80 (1.39) 3,955 (35.10)
Mixed racial group 1 (0.02) 3 (0.03)
Other racial group 1,501 (26.05) 426 (3.78)
Unknown racial group 500 (8.68) 228 (2.02)
White 3,632 (63.04) 5,593 (49.63)
Ethnicity
    Hispanic 3,632 (36.34) 80 (1.90)
BMI
    Median (IQR) 28.9 (25.0, 34.1) 30.7 (26.0, 37.0) 29.3 (25.9, 34.0) 29.2 (24.9, 35.0)
    <25 1,816 (25.49) 778 (20.36) 1,281 (33.62) 2,781 (28.49)
    25–29.9 2,202 (30.91) 983 (25.73) 753 (19.76) 2,509 (25.70)
    ≥30 3,106 (43.6) 2,060 (53.91) 1,776 (46.61) 4,471 (45.80)
ZIP (first digit)*
    0 1,299 (14.97) 670 (16.55) 501 (10.06) 1,766 (16.25)
    1 751 (8.66) 206 (5.09) 217 (4.36) 995 (9.15)
    2 634 (7.31) 1,841 (45.47) 100 (2.01) 2,524 (23.22)
    3 1,654 (19.07) 481 (11.88) 1,289 (25.87) 941 (8.66)
    4 829 (9.56) 314 (7.76) 143 (2.87) 1,076 (9.90)
    5 93 (1.07) 15 (0.37) 22 (0.44) 90 (0.83)
    6 321 (3.7) 82 (2.03) 69 (1.38) 411 (3.78)
    7 797 (9.19) 158 (3.90) 571 (11.46) 484 (4.45)
    8 380 (4.38) 121 (2.99) 244 (4.9) 1,054 (9.70)
    9 1,917 (22.10) 161 (3.98) 1,826 (36.65) 1,528 (14.06)
Insurance
    Uninsured 587 (5.87) 151 (3.58) 557 (9.67) 333 (2.96)
    Medicare 3,098 (31.00) 1,442 (34.21) 807 (14.01) 4,187 (37.16)
    Medicaid 1,042 (10.43) 704 (16.70) 1,022 (17.74) 1,448 (12.85)
    Government 166 (1.66) 78 (1.85) 70 (1.22) 241 (2.14)
    Private 3,185 (31.87) 1,232 (29.23) 1,710 (29.68) 3,274 (29.05)
    Other 239 (2.39) 50 (1.19) 124 (2.15) 267 (2.370)
    Missing 1,677 (16.78) 558 (13.24) 1,471 (25.53) 1,519 (13.48)
Comorbidities
N (%) with comorbidity data available 7,437 (74.41) 3,228 (76.58) 3,857 (66.95) 8,582 (76.16)
    Diabetes 2,114 (28.43) 1,205 (37.33) 1,144 (29.66) 2,783 (32.43)
    Hypertension 3,692 (49.64) 1,940 (60.10) 1,645 (42.65) 4,788 (55.79)
    Heart Failure 1,110 (14.93) 545 (16.88) 398 (10.32) 1,452 (16.92)
    ESRD 273 (3.67) 313 (9.70) 202 (5.24) 500 (5.83)
    COPD 1,036 (13.93) 357 (11.06) 253 (6.56) 1,231 (14.34)
    Asthma 701 (9.43) 414 (12.83) 318 (8.24) 920 (10.72)
    Coronary artery disease 1,517 (20.40) 576 (17.84) 528 (13.69) 1,793 (20.89)

*ZIP: ZIP code data exclude those with missing ZIP code

*p-value for differences by race and ethnicity all <0.001 with two exceptions: difference in coronary artery disease by race p-value was 0.03, and diabetes prevalence difference by ethnicity p-value was 0.002.

IQR = interquartile range, ESRD = end stage renal disease, COPD = chronic obstructive pulmonary disease

Table 1 also shows characteristic of adults stratified by ethnicity. Among those for whom ethnicity data were available (n = 17,030), n = 5,761 were Hispanic (33.8%) while 11,269 were non-Hispanic. Compared with non-Hispanic adults, Hispanic patients were older, more likely to be male, and less likely to be non-white race. Statistically significant differences were also seen in the geographic distribution of patients by ethnicity as well as the insurance type. Rates of comorbidities including diabetes, hypertension, heart failure, COPD, asthma, and CAD were all lower in Hispanic adults, while ESRD and was slightly higher.

Factors associated with mortality

Of the 19,584 patients included, n = 4050 (20.7%) died during the hospital stay. Table 2 shows characteristics of adults overall and stratified by in-hospital mortality. Among those that died, the median length of stay was 7.9 days (interquartile range 3.6–14.5 days). Among those who were discharged alive, median length of stay was 4.5 days (IQR 2.4–8.1 days). Complication rates were low overall: 4.96% of patients had a myocardial infarction, 1.47% had stroke, 1.80% ventricular tachycardia, and 2.03% pulmonary embolism.

Table 2. Characteristics of adults hospitalized with COVID-19 overall and stratified by in-hospital mortality.

Overall In-Hospital Mortality Discharged Alive
Overall sample 19,584 4,050 (20.68) 15,534 (79.32)
Length of stay
    Median (IQR) 4.97 (2.55, 9.15) 7.89 (3.60, 14.47) 4.54 (2.38, 8.05)
Age
    Median (IQR) 52 (37, 65) 75 (64, 84) 49 (35, 61)
    18–39 3,272 (16.71) 89 (2.02) 3,183 (20.49)
    40–49 2,597 (13.26) 132 (3.26) 2,465 (15.87)
    50–59 3,897 (19.9) 421 (10.40) 3,476 (22.38)
    60–69 3,974 (20.29) 820 (20.25) 3,154 (20.30)
    70–79 3,058 (15.61) 1,084 (26.77) 1,974 (12.71)
    80–89 2,775 (14.17) 1,498 (36.99) 1,277 (8.22)
    ≥90 11 (0.06) 6 (0.15) 5 (0.03)
Sex
    Female 9,294 (47.46) 1,689 (41.7) 7,605 (48.96)
    Male 10,243 (52.3) 2,353 (58.1) 7,890 (50.79)
    Other/missing 47 (0.24) 8 (0.20) 39 (0.24)
Race
    American Indian or Alaska 474 (2.42) 114 (2.81) 360 (2.32)
    Asian or Pacific islander 679 (3.47) 134 (3.31) 545 (3.51)
    Black or African American 4,215 (21.52) 955 (23.58) 3,260 (20.99)
    Mixed racial group 4 (0.02) 1 (0.02) 3 (0.02)
    Other racial group 3,201 (16.34) 497 (12.27) 2,704 (17.41)
    Unknown racial group 1,017 (5.19) 271 (6.69) 746 (4.8)
    White 9,994 (51.03) 2,078 (51.31) 7,916 (50.96)
Ethnicity
    Ethnic group unknown 2,554 (13.04) 503 (12.42) 2,051 (13.20)
    Hispanic or Latino 5,761 (29.42) 732 (18.07) 5,029 (32.37)
    Not Hispanic or Latino 11,269 (57.54) 2,815 (69.51) 8,454 (54.42)
BMI
    Mean (STD) 30.46 (7.31) 29.11 (7.67) 30.66 (7.23)
    <25 3,624 (18.5) 1,101 (27.19) 2,523 (16.24)
    25–29.9 4,801 (24.51) 1,037 (25.6) 3,764 (24.23)
    ≥30 7,118 (36.35) 1,275 (31.48) 5,843 (37.61)
    N missing 4,041 (20.63) 637 (15.73) 3,404 (21.91)
ZIP
    0 3,094 (15.8) 964 (23.8) 2,130 (13.71)
    1 1,608 (8.21) 466 (11.51) 1,142 (7.35)
    2 3,260 (16.65) 733 (18.1) 2,527 (16.27)
    3 2,263 (11.56) 273 (6.74) 1,990 (12.81)
    4 1,256 (6.41) 211 (5.21) 1,045 (6.73)
    5 120 (0.61) 8 (0.20) 112 (0.72)
    6 499 (2.55) 85 (2.10) 414 (2.67)
    7 1,103 (5.63) 244 (6.02) 859 (5.53)
    8 1,353 (6.91) 288 (7.11) 1,065 (6.86)
    9 3,441 (17.57) 609 (15.04) 2,832 (18.23)
    Insurance
    Uninsured 1,057 (5.4) 76 (1.88) 981 (6.32)
    Medicare 5,459 (27.87) 2,138 (52.79) 3,321 (21.38)
    Medicaid 2,939 (15.01) 304 (7.51) 2,635 (16.96)
    Government 322 (1.64) 45 (1.11) 277 (1.78)
    Private 5,945 (30.36) 657 (16.22) 5,288 (34.04)
    Other 418 (2.13) 163 (4.02) 255 (1.64)
    Missing 3,444 (17.59) 667 (16.47) 2,777 (17.88)
    Complications*
    Myocardial Infarction 959 (4.96) 532 (13.33) 427 (2.78)
    Stroke 284 (1.47) 159 (3.98) 125 (0.81)
    Ventricular tachycardia 349 (1.80) 202 (5.06) 147 (0.96)
    Pulmonary embolism 393 (2.03) 104 (2.61) 289 (1.88)
    Total Length of Stay (days) 4.99 (2.57, 9.17) 7.88 (3.59, 14.47) 4.56 (2.40, 8.06)

*Complications data excludes n = 241 overall (59 who died and 182 who survived) who are missing diagnoses data from hospitalization to evaluate complication rates

**All p-values <0.0001 comparing in-hospital mortality vs discharged alive

IQR = interquartile range, STD = standard deviation, ESRD = end stage renal disease, COPD = chronic obstructive pulmonary disease BMI = body mass index

Statistically significant differences (p<0.05) were seen in survival across a number of demographic and clinical variables with increasing mortality seen in older adults, males, those with comorbidities, by ZIP code, insurance status, and BMI. Age and BMI were nonlinear in their association with mortality and were modeled using restricted cubic splines (S1 and S2 Figs). Time of admission was also associated with changes in the risk of mortality in a nonlinear fashion with increasing mortality early, peaking in mortality around May, and then decreased through the first three quarters of 2020 (S3 Fig).

Mortality and complications by race and ethnicity

Table 3 shows rates of mortality and complications among adults hospitalized with COVID-19 by race and ethnicity. Among the n = 4215 Black adults, 955 (22.7%) died, whereas n = 2078 of 9994 (20.8%) white adults died, a difference that was statistically significant in univariable analysis (OR 1.12, 95% CI 01.02–1.22, p = 0.013).

Table 3. Mortality and complications among Black, white, Hispanic, and non-Hispanic adults hospitalized for COVID-19.

Black N = 4215 White N = 9994 OR (Black vs white) p-value Hispanic N = 5761 Non-Hispanic N = 11,269 OR p-value
Mortality 955 (22.66) 2078 (20.79) 1.11 (1.02–1.22) 0.014 732 (12.71%) 2815 (24.98%) 0.44 (0.40–0.48) <0.001
Myocardial Infarction 214 (5.17) 487 (4.91) 1.04 (0.89–1.23) 0.53 234 (4.09) 603 (5.45) 0.75 (0.64–0.87) <0.001
Stroke 76 (1.83) 137 (1.38) 1.32 (1.00–1.75) 0.045 47 (0.82) 185 (1.67) 0.49 (0.36–0.68) <0.001
Pulmonary Embolism 105 (2.53) 174 (1.76) 1.44 (1.13–1.84) 0.002 78 (1.36) 263 (2.38) 0.57 (0.45–0.74) <0.001
Ventricular Tachycardia 116 (2.80) 194 (1.96) 1.43 (1.13–1.80) 0.003 65 (1.14) 243 (2.20) 0.52 (0.39–0.68) <0.001
Length of Stay Among those Discharged alive 4.65 (2.49, 8.10) 4.25 (2.24, 7.68) 0.024 4.37 (2.25, 7.92) 4.55 (2.42, 8.01) 0.99
LOS Among deceased 7.94 (3.98, 13.87) 7.02 (3.11, 13.49) 0.75 9.07 (4.21, 17.94) 7.21 (3.29, 13.20) <0.0001

+ 69 white and 68 black adults were missing diagnoses codes from hospital stay to determine complications and excluded from the denominator for these calculations, leaving 5724 Hispanic, 11073 non-Hispanic, 5733 white, and 3151 Black adults for the denominator for complications

Non-Hispanic adults had higher mortality rates than Hispanic adults (12.7% vs 25.0%, OR 0.44, 95% CI 0.40–0.48, p<0.001). In addition to mortality, Hispanic adults had lower rates of complications of COVID-19 including lower rates of myocardial infarction, stroke, ventricular tachycardia, and pulmonary embolism (p<0.001 for all). Compared with White adults, Nlack adults had similar rates of myocardial infarction, but higher rates of stroke, ventricular tachycardia, and pulmonary embolism.

In multivariable modeling adjusting for demographic factors (age, sex, race, ethnicity, ZIP code and time of admission), Black race was associated with increasing risk of mortality (OR 1.13, 95% CI 1.01–1.27 compared with white race), and Hispanic ethnicity was associated with lower risk of mortality (OR 0.74, 95% CI 0.65–0.83).

Adjusting for demographic factors, race, and ethnicity, BMI, asthma, diabetes, heart failure, and chronic kidney disease were also associated with the risk of mortality (S3 Table). However, after comorbidities and BMI were included in the model, racial differences were attenuated and no longer statistically significant (Fig 1, OR for Black vs white: 1.07, 95% CI 0.93–1.23), while differences by ethnicity remained statistically significant (OR for Hispanic vs non-Hispanic 0.71, 95% CI 0.59–0.86).

Fig 1. Association between Black race and Hispanic ethnicity and inpatient mortality.

Fig 1

The figure shows odds ratios and 95% confidence intervals (CI) for race (Black vs white) and ethnicity (Hispanic vs non-Hispanic) in unadjusted models (Model 0, black diamond), adjusting for demographic characteristics (Model 1, white circle), and comorbidities and body mass index (model 2, grey square).

Discussion

In a nationwide, EHR-based database of 19,584 patients from 52 health systems across the United States, mortality among patients hospitalized for COVID-19 was higher in Black patients compared with white patients. This increasing risk of mortality remained statistically significant after adjusting for demographics such as age and sex. However, Black patients with COVID-19 had a higher burden of comorbid illnesses. As a result, after adjusting for comorbidities racial differences in mortality were no longer statistically significant. In contrast, Hispanic adults had lower overall mortality than non-Hispanic adults, a finding that remained statistically significant even after accounting for demographic and clinical differences among those hospitalized.

Prior findings regarding the association between race, ethnicity, and mortality after hospitalization are mixed. In one single-center study from an academic Medical Center in New York, Black and Hispanic patients hospitalized with COVID-19 had lower mortality rates overall, which remained statistically significant even after adjusting for age, sex, socioeconomic status, and comorbidities [12]. Other studies from either single centers or regions or specialized populations found either lower rates of mortality in Hispanic and Black adults or no association in multivariable adjusted analyses [49, 13]. Recent data from a national prospective registry found that Black and Hispanic adults represented a disproportionate number of those hospitalized with COVID-19 compared with the general population. In unadjusted analyses, both Hispanic adults and Black adults had lower all-cause mortality compared with non-Hispanic white adults, though these differences were not statistically significant after adjusting for age, medical history, and sociodemographic factors [7].

The findings of this multi-center study with larger patient numbers are slightly different from these prior reports, as Black race did appear to be a risk factor for mortality in unadjusted models and in models adjusting for demographics. However, consistent with other findings, once comorbidities were included the association between Black race and increasing mortality was no longer statistically significant.

This finding should be interpreted with caution. That adjusting for comorbidities attenuated the association between race and mortality does not indicate that there are no differences in mortality from COVID-19 by race particularly given the disproportionate burden of comorbidities associated with increased risk of complications and mortality from COVID-19 such as obesity, hypertension, diabetes, and chronic kidney disease in Black adults in the United States [14]. Rather, our findings suggest that a significant proportion of the difference in mortality between Black and white adults hospitalized with COVID-19 can be attributed to differences in the underlying burden of these comorbidities.

In contrast to race, we did find differences in survival among patients hospitalized with COVID-19 by ethnicity, with Hispanic ethnicity being associated with lower mortality. Compared with non-Hispanic patients, Hispanic patients were older and slightly more likely to be male, but had lower rates of most comorbidities including diabetes, hypertension, and coronary artery disease. In both univariable and multivariable analysis adjusting for these differences, Hispanic ethnicity remained associated with lower mortality. This has been shown in a multi-center study in the past: in a large registry, Hispanic adults had lower mortality compared with non-Hispanic adults, though this difference did not remain statistically significant after multivariable adjustment [7].

On the relative scale, the increased mortality seen in Black compared with white adults hospitalized with COVID-19 is still far less than the relative differences in mortality seen in the overall population [3]. However, compared with their overall representation in the general population, Black and Hispanic adults represented a much greater proportion of patients hospitalized with COVID-19 in our dataset. Specifically, nationwide, 13% of persons in the United States are Black, whereas 22% of patients in our dataset were Black. Similarly, Hispanic persons make up 19% of the overall population, far less than the 29% of patients hospitalized with COVID-19 in our dataset [15]. Thus, we conclude that the disproportionate burden of mortality in Black and Hispanic communities most likely represents their increased prevalence of COVID-19 infections rather than differences in outcome among those hospitalized [1, 2].

Our study also demonstrates the sobering severity of COVID-19. Overall, over 1 in 5 adults hospitalized with COVID-19 died during their inpatient stay, including over 50% of those hospitalized age 80 and older, highlighting the critical need to increase immunization efforts to curb the pandemic. Black adults are less likely to report willingness to be vaccinated, largely due to concern about side effects and decreased reported trust in vaccines [16]. Efforts are needed to improve educational efforts about vaccine safety and efficacy in high-risk communities with a focus on Black communities in order to maximize the impact of vaccination in reducing health disparities [13]. In addition to education to improve vaccine acceptance, vaccine delivery systems should focus on highest risk communities. However, early data raise the concern that Black and Hispanic persons are receiving a lower proportion of vaccines compared with white persons, potentially due to differential access to vaccine [17]. Unfortunately, efforts to prioritize Black and Hispanic at-risk communities have been prohibited in at least one large metropolitan area [18].

This study has several important limitations. First, race and ethnicity were based on EHR data, which is usually captured by patient self-report, but is subject to potential errors in both data entry and incomplete data capture. Our data on race and ethnicity reflect these as social constructs and not biological ones which would have required genetic ancestry. Other limitations of using data from the electronic medical record include incomplete capture of patient comorbidities particularly among those who did not receive care at that institution previously. Excluding those without prior comorbidity data did not appear, however, to impact our mortality estimates: The overall mortality in the sample was 21%, compared with 20% among those who had prior comorbidity data available. Finally, we defined COVID-19 illness using either a positive laboratory test or a clinical diagnosis of COVID-19. This may have included some cases that were misdiagnosed clinically without lab confirmation, or patients hospitalized for other reasons who were incidentally determined to be infected with COVID-19 based on screening lab tests. Finally, discharge status was unavailable in 6.5% of patients, and 16.6% were transferred to another facility, so their ultimate outcomes were unknown. If transfers were variable by race, and survival was different among those who were transferred vs remained hospitalized, this may have impacted our findings, which may only apply to those patients who remain hospitalized.

Conclusion

Black adults hospitalized for COVID-19 had higher in-hospital mortality than white adults due to increased prevalence of comorbidities that increase the risk of death among adults hospitalized with COVID-19. In contrast, Hispanic adults had lower mortality rates even after accounting for differences in patients hospitalized with disease.

Supporting information

S1 Fig

(JPG)

S2 Fig

(JPG)

S3 Fig

(JPG)

S1 Table

(PDF)

S2 Table

(PDF)

S3 Table

(PDF)

Data Availability

Data from the Cerner Real World Data COVID dataset are available on request to Cerner corporation (contact via Kendra.Stillwell@Cerner.com). Per the user agreements between Cerner and the contributing health systems, all research requests must be approved by the governance council which consists of representatives from both Cerner and contributing health systems. Upon approval, researchers can access the de-identified datasets on the Cerner platform; individual patient data (even de-identified data) are never released outside of the analytic environment to protect patient confidentiality based on the agreements in place between Cerner and participating sites.

Funding Statement

This study was supported by Cerner Corporation who provided access to the dataset and employee time to participate on the research study. The dataset for this study was created by Cerner for use by academic researchers with support from Amazon Web Services, and is available for access to external researchers upon request. Cerner Corporation-employed co-authors (QH, RT, SP) received salary from Cerner corporation during the time they participated on this research project. Cerner Corp. provided in-kind support for the study through their effort and through providing access to data. Cerner Corp. co-authors were a part of the study team and had roles in creating the dataset and data acquisition (RT, SP), data analysis (QH), the concept and design of the study, data interpretation, and critical revision of the manuscript (QH, RT, SP). EP and AMN receive fees for research consulting to Cerner Corporation outside of the present work. EP and AMN were not compensated for their work on this manuscript.

References

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Decision Letter 0

Francesco Di Gennaro

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

22 Apr 2021

PONE-D-21-07038

The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

PLOS ONE

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"This study was supported by Cerner Corporation who provided access to the dataset and employee time to participate on the research study. The dataset for this study was created by Cerner for use by academic researchers with support from Amazon Web Services, and is available for access to external researchers upon request. Ann Marie Navar and Eric Peterson receive support for consulting to Cerner Corporation for activities outside of this work, but were not compensated for work on this analysis. Rob Taylor, Qingjiang Hou, and Stacey Purinton are employees of Cerner Corporation. They were not compensated for their work on this study beyond their regular salary for employment with Cerner."

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Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

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Reviewer #2: Yes

**********

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Reviewer #2: Yes

**********

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Reviewer #1: Reviewer comment for PLOS ONE

Date of review: 14 April 2021

Manuscript Number: PONE-D-21-07038

Article Type: Research Article

Full Title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

Suggested title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19 in the United States

Corresponding Author: Ann Marie Navar, UT Southwestern: The University of Texas Southwestern Medical Center, Dallas, UNITED STATES

Reviewer comment

Summary of the research and overall impression

This manuscript identified whether race and ethnicity impact on risk of death among those hospitalized for COVID-19 in the US. Generally, the paper presented well. The introduction is short and required to add more data about the burden of the disease and background situation in the hospitals or States included in the study. Methods session presents how the analysis was carried out. Results are comprehensive, however, a few editions are suggested.

BTW, I don’t see the line number in the manuscript in PDF version and it is difficult to provide the direction of the comments.

Discussion on specific area of improvement

Abstract

Well-written and clearly presented abstract.

1. Results - line 3: “[22.7% vs 20.8%, unadjusted 1.12 (95% CI 1.02-. I think it should be unadjusted OR 1.12.

2. The paper was said “in adult”, please add the mean (or median) age of participants in the results.

Introduction

3. Introduction is too short; it is incomplete information. Suggest to add more data on COVID-19 pandemic outbreak prevalence of (burden) across the US, differences in States, proportion of hospitalized patient and mortality rates, etc. (burden of disease)

4. Suggest to include other studies findings on race and ethnicity diversion on disease burden and mortality in other infectious diseases and any literature on COVID-19 in other countries. No data is the data to present. (gap in knowledge)

5. Suggest to add how race and ethnicity can influence for diagnosis and treatment for preventing life-threatening situation or reduce the mortality in certain diseases, more appropriately with infectious diseases or COVID-19. (gap in knowledge)

6. Lastly, why this study is important to conduct (justification) and how this study can provide information or input to the health system.

Materials and methods

7. Pg. 10, 3rd paragraph, 1st line: “ICD-10 diagnosis codes” – please spell this out and add reference.

8. Pg. 10, 3rd paragraph, 3rd line: “Cerner EHR” – please spell this out. Add reference for using cut off point for obesity.

Results

9. Pg. 12, 1st paragraph: to add text about age (said “younger”, but please specify), sex and geographic distribution of cases

10. Pg. 12, the title is not matched with the text, it is talking about “demographic characteristics and comorbidity of the cases”, not “race and ethnicity”

11. Again, the paragraph does not refer to any table. Please add reference table for the data presented in the text.

12. Tables: the data (numbers) is suggested to right-aligned, rather than centered.

13. Pg. 18, table 3: Please add odds ratios (OR) and CI in the tables. You may use * for p-values that are significant (eg. *p<0.001, #p<0.01)

Discussion and conclusions

14. Pg. 19, 1st paragraph, line 1: please use the exact sample size, do not use “nearly 20,000 patients” and use “52 health systems”.

15. Pg. 20, 2nd paragraph: line 1-3: please add reference.

Recommendation

I would like to propose the minor revision for this manuscript.

Please add the ethical approval number from Duke University.

Reviewer #2: The investigators conducted a retrospective cohort study to evaluate, among patients hospitalized for COVID-19, the differences in race and ethnicity and their association with death.

The manuscript is presented clearly and concisely. The following comments may help in improving the manuscript.

General

1. Persons/patients, consider using one uniformly.

2. Mortality/death consider using one uniformly.

3. clinical comorbidities/comorbidities consider using one uniformly.

Methods

1. “..we utilized any available encounter within 3 years of and including the analysis hospitalization”. Consider revising this text for clarity.

2. “those discharged on hospice”. Should it be“to” instead of “on”?

Results

1. Consider reporting, % of participants for whom data on race and ethnicity were missing.

2. “Compared with White adults, black adults had similar rates of myocardial infarction, but higher rates of myocardial infarction, stroke, ventricular tachycardia, and pulmonary embolism.” In this sentence, should the text “but higher rates of myocardial infarction” be omitted?

Tables

1. Expand abbreviations in footnotes (e.g. ESRD)

2. There is no data in Table 1 on complications, and survival, consider revising the Table title

Discussion

1. Outcome (mortality) data for a significant proportion of participants (about 31%) was not available. Consider mentioning this as a limitation and its likely implications.

Conclusion

1. Consider revising to exclude redundant text and for clarity.

**********

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Reviewer #1: Yes: Poe Poe Aung

Reviewer #2: No

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Attachment

Submitted filename: Reviewer comment_PONE-D-21-07038_14Apr2021.docx

PLoS One. 2021 Jul 21;16(7):e0254809. doi: 10.1371/journal.pone.0254809.r002

Author response to Decision Letter 0


10 Jun 2021

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

RESPONSE: The manuscript has been reformatted as requested to align with guidelines.

2. Thank you for providing the following Funding Statement:

"This study was supported by Cerner Corporation who provided access to the dataset and employee time to participate on the research study. The dataset for this study was created by Cerner for use by academic researchers with support from Amazon Web Services, and is available for access to external researchers upon request. Ann Marie Navar and Eric Peterson receive support for consulting to Cerner Corporation for activities outside of this work, but were not compensated for work on this analysis. Rob Taylor, Qingjiang Hou, and Stacey Purinton are employees of Cerner Corporation. They were not compensated for their work on this study beyond their regular salary for employment with Cerner."

We note that one or more of the authors is affiliated with the funding organization, indicating the funder may have had some role in the design, data collection, analysis or preparation of your manuscript for publication; in other words, the funder played an indirect role through the participation of the co-authors.

If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study in the Author Contributions section of the online submission form. Please make any necessary amendments directly within this section of the online submission form.

Please also update your Funding Statement to include the following statement: “The funder provided support in the form of salaries for authors [insert relevant initials], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”

If the funding organization did have an additional role, please state and explain that role within your Funding Statement.

Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc.

Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

RESPONSE: Cerner was not a “funder” in the sense that funds were made available to the project, which is why we didn’t include them initially. This has been added and that box has checked. We took this information out of the “acknowledgement section” per formatting requirements.

A funding statement is now in the comments section of the submission system:

Cerner provided in-kind support for the study by providing access to data and through the work of Cerner co-authors. Cerner co-authors would have received their regular salary during the course of their work on this project, but this was not linked directly to this manuscript

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

The competing interests statement is now in the comments section of the submission system, and author contributions are clearly defined in the manuscript:

RESPONSE: The updated financial statement provided outlines this information now in more detail:

Cerner Corporation-employed co-authors (QH, RT, SP) received salary from Cerner corporation during the time they participated on this research project. Cerner Corp. provided in-kind support for the study through their effort and through providing access to data. Cerner Corp. co-authors were a part of the study team and had roles in creating the dataset and data acquisition (RT, SP), data analysis (QH), the concept and design of the study, data interpretation, and critical revision of the manuscript (QH, RT, SP). EP and AMN receive fees for research consulting to Cerner Corporation outside of the present work. EP and AMN were not compensated for their work on this manuscript.

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

RESPONSE: Thank you for the opportunity to clarify. We have added this information to the cover letter:

Data from the Cerner Real World Data COVID dataset are available on request to Cerner corporation Kendra.Stillwell@Cerner.com. Per the user agreements between Cerner and the contributing health systems, all research requests must be approved by the governance council which consists of representatives from both Cerner and contributing health systems. Upon approval, researchers can access the de-identified datasets on the Cerner platform; individual patient data (even de-identified data) are never released outside of the analytic environment to protect patient confidentiality based on the agreements in place between Cerner and participating sites.

This has also been clarified in the manuscript.

Per the user agreements between Cerner and participating health systems, individual patient data cannot be shared externally but approved researchers can access the data for individual studies.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

RESPONSE: The supplement has been edited to include a figure captain for all captions.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

RESPONSE: Thank you to the reviewers for the thoughtful and thorough reviews, which have strengthened our manuscript.

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

RESPONSE: See above for edits on the data sharing statements

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

________________________________________

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewer comment for PLOS ONE

Date of review: 14 April 2021

Manuscript Number: PONE-D-21-07038

Article Type: Research Article

Full Title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

Suggested title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19 in the United States

Corresponding Author: Ann Marie Navar, UT Southwestern: The University of Texas Southwestern Medical Center, Dallas, UNITED STATES

Reviewer comment

Summary of the research and overall impression

This manuscript identified whether race and ethnicity impact on risk of death among those hospitalized for COVID-19 in the US. Generally, the paper presented well. The introduction is short and required to add more data about the burden of the disease and background situation in the hospitals or States included in the study. Methods session presents how the analysis was carried out. Results are comprehensive, however, a few editions are suggested.

BTW, I don’t see the line number in the manuscript in PDF version and it is difficult to provide the direction of the comments.

Discussion on specific area of improvement

Abstract

Well-written and clearly presented abstract.

1. Results - line 3: “[22.7% vs 20.8%, unadjusted 1.12 (95% CI 1.02-. I think it should be unadjusted OR 1.12.

RESPONSE: This has been corrected – thank you

2. The paper was said “in adult”, please add the mean (or median) age of participants in the results.

RESPONSE: This has been added as requested

Through August 2020, 19,584 patients with median age 52 years were hospitalized with COVID-19, including n=4,215 (21.5%) Black and n=5,761 (29.4%) Hispanic persons

Introduction

3. Introduction is too short; it is incomplete information. Suggest to add more data on COVID-19 pandemic outbreak prevalence of (burden) across the US, differences in States, proportion of hospitalized patient and mortality rates, etc. (burden of disease)

RESPONSE: We added data on the burden of disease in COVID-19 to the first paragraph of the intro

The COVID-19 pandemic caused approximately 375,000 deaths in the United States in 2020, and was either the cause of death or contributing cause of death for 11.3% of all deaths in the United States.[ ] Likely due to COVID-19, the age-adjusted mortality increased in the United States by 15.9% in 2020.[ ] Among patients hospitalized for COVID-19, the mortality rate has generally decreased over time, but has been shown to vary across hospitals, with one study showing a 50% variability in risk-standardized event rates of mortality or referral to hospice among COVID-19 patients in the first six months of the pandemic.[ ]

4. Suggest to include other studies findings on race and ethnicity diversion on disease burden and mortality in other infectious diseases and any literature on COVID-19 in other countries. No data is the data to present. (gap in knowledge)

RESPONSE: As this study is focused on the US we did not include race/ethnicity data on COVID-19 from other countries.

5. Suggest to add how race and ethnicity can influence for diagnosis and treatment for preventing life-threatening situation or reduce the mortality in certain diseases, more appropriately with infectious diseases or COVID-19. (gap in knowledge)

RESPONSE: We added the following to the introduction

Accurate information regarding the impact of race and ethnicity on outcomes is important to help physicians identify higher risk patients when admitted, to identify potential biological mechanisms affecting prognosis, and to target public health interventions appropriately. Most importantly, differences in outcomes by race and ethnicity may serve as an indicator of systemic biases in the healthcare system, with differential treatment leading to differential outcomes.

6. Lastly, why this study is important to conduct (justification) and how this study can provide information or input to the health system.

RESPONSE: See response to the above comment which we feel highlights the importance of understanding variability by race

Materials and methods

7. Pg. 10, 3rd paragraph, 1st line: “ICD-10 diagnosis codes” – please spell this out and add reference.

RESPONSE: This has been spelled out. We noted an error in that we also used MEDCIN and SNOMED codes, this has been clarified in the manuscript. We don’t have a specific reference for ICD-10.

8. Pg. 10, 3rd paragraph, 3rd line: “Cerner EHR” – please spell this out. Add reference for using cut off point for obesity.

RESPONSE: EHR has been fully spelled out. This is a universally used cutoff for BMI for obesity.

Results

9. Pg. 12, 1st paragraph: to add text about age (said “younger”, but please specify), sex and geographic distribution of cases

RESPONSE: We added the numbers into the text for this section as requested.

Overall, 51.0% (n=9994) of our sample was white while 21.5% were recorded as Black (n=4215). Table 1 shows differences between Black and white adults admitted with COVID-19. Black adults were younger (median age 59 vs 62 years), less likely to be male (47.3% vs 53.0%), less likely to be Hispanic (1.9% vs 36.3%), had higher BMIs (median BMI 30.7 vs 38.9), and different distribution of insurance coverage (p<0.001 for all). Black patients also had higher rates of diabetes, hypertension, coronary artery disease, heart failure, chronic kidney disease, and end stage renal disease, and lower rates of COPD and asthma (see Table 1).

10. Pg. 12, the title is not matched with the text, it is talking about “demographic characteristics and comorbidity of the cases”, not “race and ethnicity”

RESPONSE: On page 12 we are discussing characteristics of patients by race and ethnicity. We discuss differences in comorbidities and demographics of cases by race and ethnicity, which is why this appears in this section.

11. Again, the paragraph does not refer to any table. Please add reference table for the data presented in the text.

RESPONSE: We have clarified this-

Of the 19,584 patients included, n=4050 (20.7%) died during the hospital stay (Table 2). Table 2 shows characteristics of adults overall and stratified by in-hospital mortality.

12. Tables: the data (numbers) is suggested to right-aligned, rather than centered.

RESPONSE: We will defer to the editors on the journal preference regarding formatting and choice of left, right, vs center aligned.

13. Pg. 18, table 3: Please add odds ratios (OR) and CI in the tables. You may use * for p-values that are significant (eg. *p<0.001, #p<0.01)

RESPONSE: We have added these ORs to this table.

Discussion and conclusions

14. Pg. 19, 1st paragraph, line 1: please use the exact sample size, do not use “nearly 20,000 patients” and use “52 health systems”.

RESPONSE: This has been corrected as follows:

In a nationwide, EHR-based database of 19,584 patients from 52 health systems across the United States

15. Pg. 20, 2nd paragraph: line 1-3: please add reference.

This intro sentence sets up the paragraph where we provide specific references.

Recommendation

I would like to propose the minor revision for this manuscript.

Please add the ethical approval number from Duke University.

RESPONSE: This has been added (Pro00105396)

Thank you to the reviewer for the thoughtful and thorough review.

Reviewer #2: The investigators conducted a retrospective cohort study to evaluate, among patients hospitalized for COVID-19, the differences in race and ethnicity and their association with death.

The manuscript is presented clearly and concisely. The following comments may help in improving the manuscript.

General

1. Persons/patients, consider using one uniformly.

RESPONSE: Except when discussing national data (and referring specifically to populations, not patients), we have changed “persons” to “patients” throughout

2. Mortality/death consider using one uniformly.

RESPONSE: We have changed “death” to “mortality” throughout

3. clinical comorbidities/comorbidities consider using one uniformly.

RESPONSE: We have simplified and use “comorbidities” throughout

Methods

1. “..we utilized any available encounter within 3 years of and including the analysis hospitalization”. Consider revising this text for clarity.

RESPONSE: This has been clarified

To determine race and ethnicity, we evaluated for the presence of an indicator of race within 3 years of and including the analysis hospitalization.

2. “those discharged on hospice”. Should it be“to” instead of “on”?

RESPONSE: Thank you- this is corrected

Results

1. Consider reporting, % of participants for whom data on race and ethnicity were missing.

RESPONSE: This has been added to the first paragraph

Race data was missing for n=1,017 (5.19%) of patients overall.

2. “Compared with White adults, black adults had similar rates of myocardial infarction, but higher rates of myocardial infarction, stroke, ventricular tachycardia, and pulmonary embolism.” In this sentence, should the text “but higher rates of myocardial infarction” be omitted?

RESPONSE: Thank you- this was an error in the text and has been corrected.

Compared with White adults, Black adults had similar rates of myocardial infarction, but higher rates of myocardial infarction, stroke, ventricular tachycardia, and pulmonary embolism.

Tables

1. Expand abbreviations in footnotes (e.g. ESRD)

RESPONSE: Thank you- these have been added

2. There is no data in Table 1 on complications, and survival, consider revising the Table title

RESPONSE: Thank you for this- we have corrected the title

Table 1: Characteristics of white, Black, Hispanic, and non-Hispanic patients hospitalized with COVID-19

Discussion

1. Outcome (mortality) data for a significant proportion of participants (about 31%) was not available. Consider mentioning this as a limitation and its likely implications.

RESPONSE: This statement is based on our note that 6.1% were still hospitalized, 1.6% went to hospice, 16.6% were transferred, and discharge status was unknown for 6.5%. We now break this down by race as well in the supplement, and discuss this in the limitations. The overall difference between Black and White patients who were transferred was 3.3%, which is unlikely to impact our findings. Similarly, while there was a higher rate of unknown discharge status in in Black / African American patients, survival would have to have been substantially different in this population to impact findings.

If transfers were variable by race, and survival was different among those who were transferred vs remained hospitalized, this may have impacted our findings, which may only apply to those patients who are not transferred.

Conclusion

1. Consider revising to exclude redundant text and for clarity.

RESPONSE: We have made revisions throughout the conclusion to help tighten up the messaging as requested.

________________________________________

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Poe Poe Aung

Reviewer #2: No

Attachment

Submitted filename: PLOS one responses to reviewers_5.13.docx

Decision Letter 1

Stanislaw Stepkowski

5 Jul 2021

The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

PONE-D-21-07038R1

Dear Dr. Navar,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Stanislaw Stepkowski

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewer comment for PLOS ONE

Date of review: 23 June 2021

Manuscript Number: PONE-D-21-07038_R1

Article Type: Research Article

Full Title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

Corresponding Author: Ann Marie Navar, UT Southwestern: The University of Texas Southwestern Medical Center, Dallas, UNITED STATES

Reviewer comment

Summary of the research and overall impression

The manuscript was revised according to the reviewer’s comment, improved and ready for publication after revising the title by adding “in the United States”.

Discussion on specific area of improvement

Suggested title: The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19 in the United States [to add the name of the country at the end of the title]

Recommendation

I would like to accept this manuscript.

Reviewer #2: The authors provided point-by-point response to the reviewers comments and have improved the manuscript.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Poe Poe Aung

Reviewer #2: No

Attachment

Submitted filename: Reviewer comment_PONE-D-21-07038_R1_23June2021.docx

Acceptance letter

Stanislaw Stepkowski

9 Jul 2021

PONE-D-21-07038R1

The Impact of Race and Ethnicity on Outcomes in 19,584 adults Hospitalized with COVID-19

Dear Dr. Navar:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Stanislaw Stepkowski

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Fig

    (JPG)

    S2 Fig

    (JPG)

    S3 Fig

    (JPG)

    S1 Table

    (PDF)

    S2 Table

    (PDF)

    S3 Table

    (PDF)

    Attachment

    Submitted filename: Reviewer comment_PONE-D-21-07038_14Apr2021.docx

    Attachment

    Submitted filename: PLOS one responses to reviewers_5.13.docx

    Attachment

    Submitted filename: Reviewer comment_PONE-D-21-07038_R1_23June2021.docx

    Data Availability Statement

    Data from the Cerner Real World Data COVID dataset are available on request to Cerner corporation (contact via Kendra.Stillwell@Cerner.com). Per the user agreements between Cerner and the contributing health systems, all research requests must be approved by the governance council which consists of representatives from both Cerner and contributing health systems. Upon approval, researchers can access the de-identified datasets on the Cerner platform; individual patient data (even de-identified data) are never released outside of the analytic environment to protect patient confidentiality based on the agreements in place between Cerner and participating sites.


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