Racial and ethnic differences in COVID-19-associated septic shock

Abstract

BACKGROUND

Septic shock, the most severe form of sepsis, remains a major global health challenge with high mortality. The coronavirus disease 2019 (COVID-19) pandemic has exacerbated this burden, as severe acute respiratory syndrome coronavirus 2 infection often leads to sepsis and septic shock. Racial and ethnic differences in critical illness outcomes are well-documented, but their impact on COVID-19 associated septic shock remains unclear.

AIM

To examine epidemiologic data to explore racial and ethnic differences in outcomes in COVID-19 associated septic shock.

METHODS

Using the National Inpatient Sample (2020–2021), we conducted a retrospective cohort study to assess racial and ethnic disparities in septic shock outcomes among adults (≥ 18 years) with concurrent COVID-19. Primary and secondary outcomes included in-hospital mortality, acute kidney injury (AKI), AKI requiring dialysis, and mechanical ventilation. Adjusted multivariable logistic regression accounted for demographics, comorbidities, hospital characteristics, and in-hospital events.

RESULTS

Among 396795 weighted hospitalizations, Non-Hispanic Black (NHB) (25.3%) and Hispanic (30.4%) populations were younger and had greater comorbidity burdens than Non-Hispanic White (NHW) patients. Compared to NHW, adjusted analyses showed higher in-hospital mortality [adjusted odds ratio (aOR) = 1.21, 95%CI: 1.15–1.27], mechanical ventilation use (aOR = 1.19, 95%CI: 1.12–1.27) and AKI requiring dialysis (aOR = 1.16, 95%CI: 1.07-1.25, P < 0.001) among Hispanic patients. NHB patients had similar mortality to NHWs but had higher risk of mechanical ventilation (aOR = 1.15, 95%CI: 1.09–1.22) and AKI requiring dialysis (aOR = 1.65, 95%CI: 1.54–1.76). Mean length of stay and cost were longest and highest for Hispanic patients.

CONCLUSION

Our study showed that there was higher mortality in Hispanic patients, and higher renal and respiratory complication in both NHB and Hispanic groups compared to NHW group. Future research identifying the causes of the observed differences in complications are required to inform targeted strategies that may mitigate modifiable risk factors and optimize early detection of organ failure to optimize outcomes in this population.

Key Words: COVID-19; Sociodemographic; Race; Ethnicity; Mortality; Septic shock; Critical care; Outcome

Core Tip: Our study highlights significant racial and ethnic differences in outcomes among patients with coronavirus disease 2019-associated septic shock, with Hispanic patients experiencing higher in-hospital mortality and Non-Hispanic Black patients facing increased risks of severe complications like acute kidney injury requiring dialysis and mechanical ventilation. These disparities are influenced by multifactorial determinants, including socioeconomic status, comorbidity burden, and hospital-level factors, emphasizing the need to address healthcare inequities and improve outcomes for minority populations.

INTRODUCTION

Septic shock, the most severe manifestation of sepsis, remains a critical global health challenge due to its high mortality rates[1]. Coronavirus disease 2019 (COVID-19) has further exacerbated this burden, as severe acute respiratory syndrome coronavirus 2 infection frequently leads to sepsis and septic shock through a dysregulated host immune response[2]. Despite substantial advances in critical care and the implementation of standardized sepsis management protocols, outcomes for patients with septic shock remain suboptimal[3]. This synergistic combination of COVID-19 and sepsis highlights the need for comprehensive research into the factors influencing patient outcomes.

Sociodemographic factors including sex, race and ethnicity have emerged as important determinants of health outcomes in many critical conditions, including sepsis and its complications[4]. Previous studies have consistently reported higher sepsis-related mortality rate among racial and ethnic minority groups, particularly African Americans and Hispanics, compared to White populations[5,6]. These disparities are attributed to complex factors, including inequities in socioeconomic status, healthcare access, comorbidity burden, and structural racism[7]. The COVID-19 pandemic has amplified these inequities, exposing disproportionate impacts on minority populations, including higher infection rates, more severe disease courses, and poorer outcomes[8]. However, the relationship between race, septic shock, and COVID-19 remains incompletely understood, with limited and often conflicting evidence on the extent and nature of racial disparities in septic shock outcomes during the pandemic.

This study aims to examine epidemiologic data to explore racial and ethnic differences in outcomes in COVID-19 associated septic shock. We hypothesize that racial and ethnic differences exist in the outcomes of septic shock associated with COVID-19, with Non-Hispanic Black (NHB) and Hispanic populations experiencing higher mortality compared to Non-Hispanic White (NHW) populations, even after accounting for sociodemographic factors.

MATERIALS AND METHODS

Study design and data source

A retrospective cohort study was conducted utilizing data from the National Inpatient Sample (NIS) database for the years 2020 and 2021. The NIS, which is part of the Healthcare Cost and Utilization Project and supported by the Agency for Healthcare Research and Quality, is recognized as the largest publicly accessible all-payer inpatient database in the United States. The database includes information from approximately 7 million hospital stays annually, representing a 20% stratified sample of discharges from United States community hospitals, excluding rehabilitation and long-term acute care facilities. Informed consent was not required for this study as it utilized publicly available, de-identified data from the NIS, which is exempt from institutional review board approval.

Patient selection and identification

Adult patients aged 18 years or older with a diagnosis of septic shock were identified using the International Classification of Diseases, 10^th Revision, Clinical Modification (ICD-10-CM) code R65.21, which has been used and validated in previous epidemiological studies. Following that, patients with COVID-19 were identified using the ICD-10-CM codes U07.1, U00, U49, U50, U85, J12.82. Patients with missing data for variables including age, sex, race/ethnicity, median household income, elective admission status, insurance type or in-hospital mortality, were excluded. Patients without COVID-19 were excluded from this study.

Study variables

Demographic variables, including age, sex, race/ethnicity, median household income and primary insurance type were extracted. Race/ethnicity was categorized as White, Black, Hispanic, and other (including Asian, Pacific Islander, Native American, and other races or ethnicities). Additional variables related to hospital characteristics (teaching status, bed size, and urban/rural classification), admission type (elective vs non-elective), and relevant comorbidities were also obtained using ICD-10-CM codes.

Outcomes

The primary outcome assessed was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), AKI requiring dialysis, mechanical ventilation, and predictors of in-hospital mortality.

Statistical analysis

Survey-based methodologies were used to account for the complex sampling structure of the NIS, with appropriate weights applied to generate national-level estimates. Statistical significance was defined as a two-sided P value < 0.05. Continuous variables were summarized as weighted means with SD or medians with interquartile ranges, as appropriate, while categorical variables were presented as weighted frequencies with percentages. Comparisons across racial/ethnic groups were performed using weighted χ² tests for categorical variables and weighted linear regression for continuous variables. Given the missing data constituted less than 5%, we performed a complete case analysis. Trends in septic shock hospitalizations and mortality rates over time were evaluated using the Cochran-Armitage test.

Multivariable logistic regression models were constructed to examine the association between race/ethnicity and in-hospital mortality. Adjustments were made for age, sex, median household income, primary insurance type, comorbidities and hospital characteristics. Additionally, multivariable logistic regression models were also used to identify predictors of in-hospital mortality. A total of 2 models were constructed; model 1 included covariates significant on univariate analysis, while model 2 included model 1 and additional adjustments for in-hospital events including AKI, AKI requiring dialysis and the need of mechanical ventilation. Adjusted odds ratios (aOR) with 95%CI were reported. All analyses were performed using STATA version 17.0.

RESULTS

In this contemporary 2-year study, 396795 septic shock hospitalizations were analyzed, comprising 227315 NHW, 76875 NHB, and 92575 Hispanic patients. The mean age of patients was 66.23 years ± 14.59 years, with NHWs averaging 67.29 years ± 14.35 years, NHBs 63.07 years ± 14.85 years, and Hispanics 60.43 years ± 15.75 years. Female representation was 42.30% overall, higher in NHBs (50.83%) compared to NHWs (38.68%) and Hispanics (37.34%) (P < 0.001). Among NHWs, 61.32% were aged 65 years or older, whereas 49.17% of NHBs and 42.05% of Hispanics were in this age group (P < 0.001). Details of baseline characteristics are available in Tables 1 and 2. Comparisons were made between NHB vs NHW (Table 1) and NHW vs Hispanic cohorts (Table 2).

Table 1 Baseline characteristics of patients between Non-Hispanic Black and Non-Hispanic White, n (%).

Variables	Non-Hispanic White (n = 227315)	Non-Hispanic Black (n = 76875)	Total (n = 304190)	P value
Female	87930 (38.68)	39075 (50.83)	128680 (42.30)	< 0.001
Age (years)	67.29 ± 14.35	63.07 ± 14.85	66.23 ± 14.59
< 65	87930 (38.68)	39075 (50.83)	127005 (41.75)	< 0.001
≥ 65	139385 (61.32)	37800 (49.17)	177185 (58.25)
Hospital bed size				0.2709
Small	51915 (22.84)	16650 (21.66)	68565 (22.54)
Medium	67930 (29.88)	22270 (28.97)	90200 (29.65)
Large	107470 (47.28)	37955 (49.37)	145425 (47.81)
Hospital teaching status				< 0.001
Rural	22925 (10.09)	3425 (4.46)	26350 (8.66)
Urban non-teaching	47590 (20.94)	12135 (15.79)	59725 (19.63)
Urban teaching	156800 (68.98)	61315 (79.76)	218115 (71.70)
Elective admission	5105 (2.25)	1210 (1.57)	6315 (2.08)	< 0.001
Primary payment coverage				< 0.001
Medicare	138045 (60.73)	41240 (53.65)	179285 (58.94)
Medicaid	18935 (8.33)	12380 (16.10)	31315 (10.29)
Private insurance	56095 (24.68)	17715 (23.04)	73810 (24.26)
Self-pay	4835 (2.13)	2300 (2.99)	7135 (2.35)
No charge	245 (0.11)	230 (0.30)	475 (0.16)
Other	9160 (4.03)	3010 (3.92)	12170 (4.00)
Median household income ($)				< 0.001
1-28999	65355 (28.75)	38495 (50.07)	103850 (34.14)
29000-35999	64670 (28.45)	17525 (22.80)	82195 (27.02)
36000-46999	55860 (24.57)	13045 (16.97)	68905 (22.65)
47000+	41430 (18.23)	7810 (10.16)	49240 (16.19)
Hospital region				< 0.001
Northeast	38145 (16.78)	12205 (15.88)	50350 (16.55)
Midwest	52215 (22.97)	13235 (17.22)	65450 (21.52)
South	100390 (44.16)	45090 (58.65)	145480 (47.83)
West	36565 (16.09)	6345 (8.25)	42910 (14.11)
Comorbidities
Congestive heart failure	58415 (25.70)	20920 (27.21)	79335 (26.08)	< 0.001
Atrial fibrillation	49580 (21.81)	10900 (14.18)	60480 (19.88)	< 0.001
Coronary artery disease	47560 (20.92)	10835 (14.09)	58395 (19.20)	< 0.001
Peripheral vascular disease	14040 (6.18)	3995 (5.20)	18035 (5.93)	< 0.001
Hypertension	148215 (65.20)	56665 (73.71)	204880 (67.35)	< 0.001
Hyperlipidemia	91575 (40.29)	27740 (36.08)	119315 (39.22)	< 0.001
Chronic lung disease	60615 (26.67)	17440 (22.69)	78055 (25.66)	< 0.001
Diabetes	89885 (39.54)	39590 (51.50)	129475 (42.56)	< 0.001
Chronic kidney disease	56795 (24.99)	27745 (36.09)	84540 (27.79)	< 0.001
Liver disease	25965 (11.42)	9445 (12.29)	35410 (11.64)	0.0085
Anemia	10740 (4.72)	5445 (7.08)	16185 (5.32)	< 0.001
Acquired immunodeficiency syndrome	320 (0.14)	600 (0.78)	920 (0.30)	< 0.001
Cancer	11860 (5.22)	3520 (4.58)	15380 (5.06)	0.0024
Coagulopathy	56165 (24.71)	20635 (26.84)	76800 (25.25)	0.0002
Obesity	67125 (29.53)	25965 (33.78)	93090 (30.60)	< 0.001
Smoking	15605 (6.86)	5170 (6.73)	20775 (6.83)	0.5673
Elixhauser comorbidity score	4.94 ± 2.13	5.20 ± 2.15	5.01 ± 2.14	< 0.001

Table 2 Baseline characteristics of patients between Hispanics and Non-Hispanic White, n (%).

Variables	Non-Hispanic White (n = 227315)	Hispanic (n = 92575)	Total (n = 319890)	P value
Female	91825 (40.40)	34565 (37.34)	126390 (39.51)	< 0.001
Age	67.29 ± 14.35	60.43 ± 15.75	65.31 (15.09)	< 0.001
Age (years)
< 65	87930 (38.68)	53645 (57.95)	141575 (44.26)
≥ 65	139385 (61.32)	38930 (42.05)	178315 (55.74)	< 0.001
Hospital bed size				0.1466
Small	51915 (22.84)	19140 (20.68)	71055 (22.21)
Medium	67930 (29.88)	27985 (30.23)	95915 (29.98)
Large	107470 (47.28)	45450 (49.10)	152920 (47.80)
Hospital teaching status				< 0.001
Rural	22925 (10.09)	1560 (1.69)	24485 (7.65)
Urban non-teaching	47590 (20.94)	18615 (20.11)	66205 (20.70)
Urban teaching	156800 (68.98)	72400 (78.21)	229200 (71.65)
				0.0022
Elective admission	5105 (2.25)	1595 (1.72)	6700 (2.09)
Primary payment coverage				< 0.001
Medicare	138045 (60.73)	36400 (39.32)	174445 (54.53)
Medicaid	18935 (8.33)	22225 (24.01)	41160 (12.87)
Private insurance	56095 (24.68)	23765 (25.67)	79860 (24.96)
Self-pay	4835 (2.13)	5985 (6.47)	10820 (3.38)
No charge	245 (0.11)	320 (0.35)	565 (0.18)
Other	9160 (4.03)	3880 (4.19)	13040 (4.08)
Median household income ($)				< 0.001
1-28999	65355 (28.75)	35125 (37.94)	100480 (31.41)
29000-35999	64670 (28.45)	24320 (26.27)	88990 (27.82)
36000-46999	55860 (24.57)	21695 (23.44)	77555 (24.24)
47000+	41430 (18.23)	11435 (12.35)	52865 (16.53)
Hospital region				< 0.001
Northeast	38145 (16.78)	11755 (12.70)	49900 (15.60)
Midwest	52215 (22.97)	5905 (6.38)	58120 (18.17)
South	100390 (44.16)	35410 (38.25)	135800 (42.45)
West	36565 (16.09)	39505 (42.67)	76070 (23.78)
Comorbidities
Congestive heart failure	58415 (25.70)	15545 (16.79)	73960 (23.12)	< 0.001
Atrial fibrillation	49580 (21.81)	12540 (13.55)	62120 (19.42)	< 0.001
Coronary artery disease	47560 (20.92)	10240 (11.06)	57800 (18.07)	< 0.001
Peripheral vascular disease	14040 (6.18)	3710 (4.01)	17750 (5.55)	< 0.001
Hypertension	148215 (65.20)	54455 (58.82)	202670 (63.36)	< 0.001
Hyperlipidemia	91575 (40.29)	31445 (33.97)	123020 (38.46)	< 0.001
Chronic lung disease	60615 (26.67)	13325 (14.39)	73940 (23.11)	< 0.001
Diabetes	89885 (39.54)	48485 (52.37)	138370 (43.26)	< 0.001
Chronic kidney disease	56795 (24.99)	20220 (21.84)	77015 (24.08)	< 0.001
Liver disease	25965 (11.42)	13545 (14.63)	39510 (12.35)	< 0.001
Anemia	10740 (4.72)	4595 (4.96)	15335 (4.79)	0.3018
Acquired immunodeficiency syndrome	320 (0.14)	260 (0.28)	580 (0.18)	0.0002
Cancer	11860 (5.22)	2800 (3.02)	14660 (4.58)	< 0.001
Coagulopathy	56165 (24.71)	26200 (28.30)	82365 (25.75)	< 0.001
Obesity	67125 (29.53)	32040 (34.61)	99165 (31.00)	< 0.001
Smoking	15605 (6.86)	3585 (3.87)	19190 (6.00)	< 0.001
Elixhauser comorbidity score	4.94 ± 2.133768	4.50 ± 2.13	4.81 ± 2.14	< 0.001
Elixhauser comorbidity score ≥ 4	167790 (73.81)	61775 (66.73)	229565 (71.76)	< 0.001

Socioeconomic characteristics

Significant differences in median household income were found across the groups (P < 0.001). The lowest income category (1-28999) was observed among NHB patients (50.07%), followed by Hispanic patients (37.94%). In contrast, NHW patients had a lower proportion in this category (28.75%). Medicare was the most common primary payer with the highest proportion among NHW patients (60.73%), followed by Hispanic patients (39.32%). Medicaid coverage was more prevalent among Hispanic patients (24.01%), compared to NHB (16.10%) and NHW patients (8.33%).

Hospital and admission characteristics

The majority of patients across all groups were admitted to large hospitals (47.8%), with NHWs having the highest proportion in rural hospitals (10.09%) and NHBs and Hispanics more often treated in urban teaching hospitals (79.76% and 78.21%, respectively). Elective admissions were low across all groups, with NHWs at 2.25%, NHBs at 1.57%, and Hispanics at 1.72%. Admissions were geographically concentrated in the South (47.83%), followed by the Midwest (21.52%), Northeast (16.55%), and West (14.11%).

Comorbidities

Congestive heart failure (CHF) was the most common cardiac comorbidity, affecting 26.08% of patients, with a higher prevalence in NHWs (25.70%) and NHBs (27.21%) compared to Hispanics (16.79%) (P < 0.001) (Tables 1 and 2). Atrial fibrillation (A-fib) was more prevalent in NHWs (21.81%) compared to NHBs (14.18%) and Hispanics (13.55%), while coronary artery disease (CAD) was higher in NHWs (20.92%) and NHBs (14.09.%) than Hispanics (11.06%). Hypertension was the most common among NHBs (73.71%), followed by NHWs (65.20%), and Hispanics (58.82%). Diabetes was most prevalent in Hispanics (52.37%), compared to NHWs (39.54%) and NHBs (51.50%). Chronic lung disease, hyperlipidemia, and obesity also showed significant variations across groups, with NHBs and Hispanics having lower rates of chronic lung disease (22.69% and 14.39%, respectively) compared to NHWs (26.67%). Additionally, the Elixhauser comorbidity score was highest in NHBs (5.20 ± 2.15) (P < 0.001), followed by NHWs (4.94 ± 2.13) and Hispanics (4.50 ± 2.13).

In-hospital outcomes

Univariate analysis revealed significant differences across racial/ethnic groups were observed in terms of in-hospital outcomes, including mortality, mechanical ventilation, AKI, and AKI requiring dialysis (Tables 3 and 4). In-hospital mortality rates were highest among Hispanic patients at 50.13%, followed by NHWs at 46.90% and NHBs at 46.12% (P < 0.001). Mechanical ventilation was more commonly required among Hispanic patients (57.70%), compared to NHBs (56.01%) and NHWs (50.40%) (P < 0.001). In terms of AKI, NHBs experienced the highest rate at 71.84%, followed by Hispanics at 59.06% and NHWs at 63.58% (P < 0.001). AKI requiring dialysis was most prevalent among NHBs (17.81%), with lower rates observed in Hispanics (13.23%) and NHWs (10.16%) (P < 0.001). The cost of hospitalization was significantly higher for Hispanic patients, averaging 80980.45, compared to NHWs at 50702.65 (P < 0.001). Similarly, the average length of stay was longest for Hispanic patients (19.21 days), followed by NHBs (16.63 days), and NHWs (14.40 days) (P < 0.001).

Table 3 In-hospital events/outcomes between Non-Hispanic Black and Non-Hispanic White, n (%).

Variables	Non-Hispanic White (n = 227315)	Non-Hispanic Black (n = 76875)	Total (n = 304190)	P value	Adjusted odds ratio1 (95%CI)	P value
In-hospital mortality	106620 (46.90)	35455 (46.12)	142075 (46.71)	0.2342	0.97 (0.92-1.02)	0.198
Mechanical ventilation	114560 (50.40)	43060 (56.01)	157620 (51.82)	< 0.001	1.15 (1.09-1.22)	< 0.001
AKI	144530 (63.58)	55230 (71.84)	199760 (65.67)	< 0.001	1.39 (1.32-1.46)	< 0.001
AKI requiring dialysis	23090 (10.16)	13690 (17.81)	36780 (12.09)	< 0.001	1.65 (1.54-1.76)	< 0.001
Cost of hospitalization	50702.65 ± 68069.31	58955.7 ± 75763.08	52790.8 ± 70187.56	< 0.001	-	-
Length of stay	14.40 ± 14.17	16.63 ± 16.40	14.97 ± 14.80	< 0.001	-	-

¹Adjusted for age, female, hospital teaching status, elective admission, insurance type, median household income, hospital region, congestive heart failure, hypertension, diabetes, anemia, cancer, chronic pulmonary disease, chronic kidney disease, liver disease, human immunodeficiency virus, obesity, alcohol use, drug use, depression.

AKI: Acute kidney injury.

Table 4 In-hospital events/outcomes between Hispanics and Non-Hispanic White, n (%).

Variables	Non-Hispanic White (n = 227315)	Hispanic (n = 92575)	Total (n = 319890)	P value	Adjusted odds ratio1 (95%CI)	P value
In-hospital mortality	106620 (46.90)	46410 (50.13)	153030 (47.84)	< 0.001	1.21 (1.15-1.27)	< 0.001
Mechanical ventilation	114560 (50.40)	53420 (57.70)	167980 (52.51)	< 0.001	1.19 (1.12-1.27)	< 0.001
AKI	144530 (63.58)	54675 (59.06)	199205 (62.27)	< 0.001	0.85 (0.81-0.90)	< 0.001
AKI requiring dialysis	23090 (10.16)	12245 (13.23)	35335 (11.05)	< 0.001	1.16 (1.07-1.25)	< 0.001
Cost of hospitalization	50702.65 ± 68069.29	80980.45 ± 105075.2	59469.76 ± 81714.79	< 0.001
Length of stay	14.40 ± 14.17	19.21 ± 19.31	15.80 ± 15.98	< 0.001

¹Adjusted for age, female, hospital teaching status, elective admission, insurance type, median household income, hospital region, congestive heart failure, hypertension, diabetes, cancer, chronic pulmonary disease, chronic kidney disease, liver disease, human immunodeficiency virus, obesity, alcohol use, drug use, depression, smoking.

AKI: Acute kidney injury.

Adjusted analyses of in-hospital outcomes

In an adjusted analysis of in-hospital outcomes comparing NHBs and Hispanics to NHWs, distinct differences were observed across several endpoints (Tables 3 and 4). For NHB vs NHW comparisons, NHB patients exhibited similar adjusted odds of in-hospital mortality (aOR = 0.97, 95%CI: 0.92-1.02, P = 0.198), but had significantly higher odds of requiring mechanical ventilation (aOR = 1.15, 95%CI: 1.09-1.22, P < 0.001), and a greater likelihood of developing AKI (aOR = 1.39, 95%CI: 1.32-1.46, P < 0.001) as well as AKI requiring dialysis (aOR = 1.65, 95%CI: 1.54-1.76, P < 0.001).

In the Hispanic vs NHW comparison, Hispanic patients showed an increased adjusted odds of in-hospital mortality (aOR = 1.21, 95%CI: 1.15-1.27, P < 0.001) and mechanical ventilation (aOR = 1.19, 95%CI: 1.12-1.27, P < 0.001), but a lower likelihood of developing AKI (aOR = 0.85, 95%CI: 0.81-0.90, P < 0.001). However, Hispanic patients had a significantly higher adjusted odds of requiring dialysis for AKI (aOR = 1.16, 95%CI: 1.07-1.25, P < 0.001).

Race/ethnicity as a predictor of in-hospital mortality

Two models evaluated mortality predictors (Supplementary Tables 1-7). Model 1, incorporating demographic and hospital factors, showed higher mortality odds for Hispanic [odds ratio (OR) = 1.24, 95%CI: 1.18-1.30, P < 0.001], Native American (OR = 1.43, 95%CI: 1.23-1.66, P < 0.001), and other races (OR = 1.18, 95%CI: 1.09-1.28, P < 0.001) compared to NHWs. Beyond race and ethnicity, we found that individuals with lower median household income and self-pay were related to higher mortality risk. Model 2, which included in-hospital events, showed that AKI, AKI requiring dialysis and need of mechanical ventilation were identified as strong predictors of mortality across all groups (Supplementary Tables 3, 5, and 7).

DISCUSSION

During this 2-year analysis we observed significant racial and ethnic differences between NHB and Hispanics when compared to NHW patients with septic shock and COVID-19 infection. The Hispanic population showed the highest mortality, followed by NHW. In contrast, Mackey et al[9] showed that NHB and hispanic populations have disproportionately higher rates of COVID-19 infection and related mortality. However, Mackey et al[9], depicted no difference in case fatality (deaths among individuals with diagnosed COVID-19). These results were not adjusted for demographic differences[10]. The root causes of these racial differences are multifactorial, namely the comorbidities burden, socioeconomic status, and geographical location.

Hospital-level factors may contribute to disparities in care. In line with prior studies, this study also demonstrates that close to 80% of Hispanics and NHBs were frequently treated in urban teaching hospitals. These are usually “non-profit safety net hospitals”, frequently understaffed and underfunded. These hospital characteristics may play a role in the disparities of sepsis care and mortality[9,11]. Mayr et al[12] have demonstrated that hospitals caring for minority patients have a higher severity of illness, multi-organ failure, and mortality[13]. We found that most admissions occurred in the southern states, which statistically have shown to have higher poverty rates[12]. Additionally, the United States 2020 census shows a higher prevalence of NHB in the southern states[14]. Hispanic populations tend to also be higher within the southern border states as well as big cities where urban teaching hospitals tend to be present[14].

Significant differences in household income were evident, with NHB and Hispanics being in the lower income brackets. Medicaid as a primary source of insurance was more prevalent in Hispanic patients, followed by NHB. Socioeconomic status is another driving force for healthcare disparities. A lower socioeconomic status may lead to less access to better education opportunities, limited access to healthier living conditions, and less care focusing on health promotion and disease prevention[15]. Unfortunately, given the study's limitations, the correlation between education level and socioeconomic status was not evaluated. Reliance on Medicaid services may limit an individual's access to provider networks and specialist care. The financial constraints of people in the lower income brackets limit their ability to pay out-of-pocket health costs, which may lead to delays in diagnosis and treatment. Interestingly, McMaughan et al[16]. found that race was not an independent risk factor for sepsis outcomes. However, socioeconomic status and geographical location heavily influenced the outcome.

Among patients with sepsis, the number of chronic comorbidities increases the risk for organ dysfunction[17]. Cardiac comorbidities (A-fib, and CAD) were more prevalent in NHW, followed by NHB and Hispanics. Nevertheless, hypertension was prevalent in all groups, while diabetes was more prevalent in Hispanics. Esper et al[18] analysis of the National Hospital Discharge Survey concluded that chronic comorbidities partially account for the healthcare disparities in sepsis[17].

Organ injuries such as respiratory failure and AKI are common complications among patients hospitalized with sepsis, which could lead to invasive medical therapy such as mechanical ventilation and renal replacement therapy[18]. The requirement of mechanical ventilation and/or renal replacement therapy in septic patients is associated with increased mortality. Consistent with current epidemiologic data, the multivariable logistic regression analysis demonstrates that AKI, AKI requiring dialysis, and the need for mechanical ventilation are significant predictors of mortality and may account in part for racial disparities in mortality. Several studies evaluating hospitalized patients with different cases have demonstrated significant racial disparities in the development of AKI, with a higher prevalence of AKI developing among NHBs[19,20]. These differences become attenuated when adjusted for comorbidities and socioeconomic status[21]. The current study showed significant differences in the development of AKI requiring dialysis, particularly among Hispanics, followed by NHB compared to their NHW counterparts. Several studies evaluating racial disparities in the use of mechanical ventilation have yielded conflicting results. Some studies demonstrate a higher frequency of mechanical ventilation utilization among NHB and other minorities, while others have not[22]. In the current analysis, the utilization of mechanical ventilation was greater among Hispanics and NHB. Notably, when adjusting for AKI, AKI requiring dialysis and mechanical ventilation, the racial differences in mortality was attenuated, signifying the influence of these secondary outcomes on in-hospital mortality. Thus, emphasis should be placed on recognizing the association between race and these complications, which could be a driver for the adverse in-hospital outcomes in these patients.

Limitations

The limitations of the current study include that this is an administrative database that relies on ICD coding, which may differ according to coding practices at the individual and hospital level; thus, the risk of misclassification bias could not be excluded. Additionally, the database is from the United States and may not be generalized to other populations. Likewise, while our study focused on adjustment for sociodemographic factors, relevant variables like education level and number of household members were not evaluated. Additionally, data on income was derived from the median household income of the patient's residence ZIP code; thus, it may only act as surrogate income data. Furthermore, the lack of data on vasopressor use, and laboratory data precluded further analysis. Lastly, some of these patients may have more than one site of infection, which has not been explored in this study. Future studies should ideally incorporate these data, including admission prognostic risk scores such as Sequential Organ Failure Assessment scores to provide a better understanding on the effect of race on the outcomes of these patients.

CONCLUSION

In patients admitted with COVID-19 associated septic shock, significant differences in mortality exist, though these disparities are attenuated when adjusting for comorbidities, socioeconomic status, hospital-level factors, and in-hospital events. While observed differences in mortality are important, greater emphasis should be placed on identifying factors influencing complications such as AKI, AKI requiring dialysis, and the need for mechanical ventilation. This includes identifying prognostic indicators and optimizing early management strategies to address these complications effectively. These findings underscore that the observed differences in outcomes are multifactorial, driven by social determinants of health and the management of comorbidities before the onset of septic shock. During the COVID-19 pandemic, ethnic disparities persisted, with pre-illness factors as the likely key drivers. Addressing these complications and their underlying determinants on a social and community level may improve outcomes and reduce mortality in minority ethnic groups.