Higher Comorbidities and Early Death is Characteristic of Hospitalized African-American Patients with COVID-19

Background African-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions. Method We performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a five-week period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black population Result Of the 1,070 consecutive patients who tested positive for COVID-19, 496 critically ill patients were hospitalized and included in the study. 88% of patients were Black; and a majority (53%) were 61-80 years old with a mean body mass index in the 'obese' range. 97% had one or more comorbidities. Hypertension was the most common (84%) pre-existing condition followed by diabetes mellitus (57%) and chronic kidney disease (24%). Patients with chronic kidney disease and end-stage renal disease who received hemodialysis were found to have significantly lower mortality, then those who did not receive it, suggesting benefit from hemodialysis (11%, OR, 0.35, CI, 0.17 - 0.69 P=0.001). Age >60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox Proportional Hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil / lymphocyte ratio (8.5, 10.0) were predictive of mortality on admission and at 48-96 hrs. Of the 496 inpatients, 48% died, one third of patients died within the first three days of admission. 54/488 patients received invasive mechanical ventilation, of which 87% died and of the remaining patients, 32% died. CONCLUSIONS COVID-19 patients in our predominantly Black neighborhood had higher mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.

Organization to be a pandemic, with over five million confirmed cases. 1 New York became 97 the epicenter of the epidemic in the United States, accounting for more than 23% of the 98 total U.S. cases by the end of May, 2020. 2 Such burden of disease is of particular concern 99 since it disproportionately affects communities with considerable health disparities, where 100 African-Americans and Latinos constitute as much as 53% of the population. 3

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The spectrum of COVID-19 presentation ranges from mild influenza-like illness to life-103 threatening severe respiratory disease requiring ventilatory support. 3 Comorbid 104 conditions such as hypertension, diabetes mellitus, pulmonary and heart diseases, and 105 demographic factors have been reported to influence outcomes. [4][5][6] However, the relative 106 influence of each of these comorbidities in different patient populations and age strata 107 has not been assessed, leading to variability in management and outcomes. Key 108 decisions in patient management such as the choice of antibiotic, blood pressure goals, 109 and perhaps most importantly, airway management strategies, have remained variable 110 across or within hospitals. 111 112 National health statistics have documented extensive health disparities for Black COVID- 113 19 patients. They suffer a three-fold greater infection rate, and a six-fold greater mortality 114 rate than their white counterparts. 7 However, clinical features and laboratory data of 115 prognostic significance from Black COVID-19 patients remain unexplored and 116 undocumented. A range of cultural, linguistic, and healthcare access barriers have 117 prevented clinical investigation. Our hospital, located in New York City, serves a 118 predominantly Black population, and being declared a COVID-only facility, we were able 119 to maintain a standard quality-of-care across all COVID-19 patients. 120 121 Here we explore the clinical aspects of COVID-19 and its outcomes in Black patients; we 122 also identify comorbidities and demographic factors that help explain the greater mortality 123 from COVID-19 observed in this vulnerable population. This study evaluated clinical signs 124 and symptoms, laboratory indicators, and management strategies to develop a data-125 driven COVID-19 patient-care approach. We evaluated these factors at admission and at 126 48-96 hours after admission, as one-third of our patients died within the first few days of 127 admission, and we found early recognition of critical indicators pivotal in assessing risk of 128 mortality. To our knowledge, this is the only study that correlates early laboratory 129 indicators at two critical time points with outcomes. Therefore, our findings are expected 130 to provide an evidence-based resource for physicians to assess patient progress within 131 the first three days of hospitalization to direct patient management decisions. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020. Hispanic/non-Hispanic and Asian). HIV-positive patients (with low CD4 counts) and 160 transplant recipients were categorized as "immunocompromised". Computational analysis was conducted using R (ver. 3.6.3). 9 Continuous variables are 178 presented as median and interquartile range (IQR). Categorical variables such as gender 179 or race are presented as number and percent of patients with 95% confidence intervals 180 (CI). Percentages are expressed based on the available data for the subgroup relative to 181 the total available data for that variable.

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. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020.  is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint results are notable considering patients with CKD/ESRD suffered higher mean number 230 of comorbidities (mean 4.2) than other patients (mean 3.3, P = <0.001) ( Table 3). 231 232 In multivariate analysis, age >60 years and CAD were independent predictors of mortality. 233 Hemodialysis in patients with CKD/ESRD was an independent predictor of lower mortality 234 (P = 0.007) (Figure 1). Cox proportional hazards analysis for time to death showed that Older age at admission correlated with higher mortality rate, with the 60+ year age group 291 most at risk, and was an independent risk factor for mortality. Males suffered significantly 292 higher mortality than females, despite identical representation at admission. Recent 293 reports of high plasma concentrations of ACE-2, a receptor for coronavirus, in men may 294 account for higher mortality. 12 Our inpatient population had a mean BMI in the "obese" 295 range, higher than the national average; this finding mirrors higher BMI amongst the Black 296 population nationwide. 13 However, BMI was not an independent predictor of survival; 297 higher BMIs were more commonly seen amongst younger patients. Smoking was less 298 prevalent in our patient population than the national average; 4% were current smokers 299 and 15% had quit. 14 We found smoking to be unrelated to poor outcome.

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The majority (88%) of our patients were Black. Race was not an independent prognostic 302 factor for survival; higher mortality in our patient population can be attributed to a greater 303 number and prevalence of comorbidities common amongst this group. Comorbidities 304 were present in 97% of our patients, and the presence of any comorbidity was a strong 305 predictor of mortality, as noted in other recent studies. 15,16 HT and DM were the two most 306 prevalent preexisting conditions; prevalence of HT (84%) and DM (57%) was 307 considerably higher than previously reported (up to 63% and 36%, respectively). [17][18][19] In 308 the multivariate analysis, coronary artery disease was strongly associated with adverse 309 outcome (OR, 2.45, CI, 1.14 -5.69, P=0.034), followed by DM (OR, 1.38, CI, 0.91 -2.11, 310 P=0.13). A 2.5-fold increase in the risk of mortality from COVID-19 in hypertensive 311 patients has been reported, however, this was not discernable in our patients. 18 Although 312 past history of cancer, HT, autoimmune diseases, and immunosuppression were not 313 independent predictors of mortality, the combined effect of these comorbidities on multiple 314 organ systems and resultant dysregulation of the immune system likely increases 315 susceptibility to COVID-19. 19,20 316 317 A notable finding in multivariate analysis was that patients with CKD who were dialyzed 318 early in the course of treatment had better outcomes than those who did not. This group 319 consisted of ESRD patients receiving continued dialysis during hospitalization and 320 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted July 16, 2020. We found laboratory data at admission vital for triaging patients to receive intensive care. Peripheral blood analysis showed that a high median NLR at admission and at 48-96 hr 343 was an independent predictor of adverse outcome in COVID-19 patients, as had been 344 reported in other studies. 24 The presence of COVID-19 associated coagulopathy (CAC), By the end of our 5-week study, 48.5% of the inpatients had died, including 87% of 355 patients who received invasive mechanical ventilation. Reported mortality rates from 356 other retrospective cohort studies ranged from 21% (New York metropolitan area) to 26% 357 (Lombardy region, Italy) and 33% (UK). 4,6,28 Our mortality rate was elevated relative to 358 other studies, which we believe is due to the largely poor and disadvantaged 359 neighborhood that our hospital serves. Race was not found to be an independent 360 predictor of mortality. The high mortality rate from COVID-19 from this predominantly 361 Black neighborhood demonstrates the large racial disparity in outcomes between these 362 patients and their counterparts elsewhere.

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Our study has limitations. It examined a predominantly Black patient cohort, which makes 365 comparisons to other races and ethnicities difficult to quantify. This study was carried out 366 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020. In our predominantly Black cohort we have recorded a mortality rate from COVID-19 375 which is significantly greater than that reported in other studies. While race was not an 376 independent predictor of death, this population had a greater burden of comorbidities than 377 the national average and the prevalence of these chronic comorbidities contributed to 378 both disease severity and higher mortality. Our study identified that early escalation of  is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint    is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020.  . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint Table 3. Mean number of comorbidities in patients with chronic kidney diseases and/or end-stage renal disease relative to all patients  is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint  . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 16, 2020. . https://doi.org/10.1101/2020.07.15.20154906 doi: medRxiv preprint