Hispanic persons living in the United States (U.S.) are at increased risk of coronavirus disease 2019 (COVID-19) infection. Although they constitute only 18.5% of the U.S. population, Hispanic individuals account for 26.2% of COVID-19 cases reported to the Centers for Disease Control and Prevention (CDC) as of October 24, 2021 [1]. However, there are conflicting data on whether COVID-19-related mortality is higher among Hispanic persons. Data from the CDC indicate a 2.3-fold higher risk of age-adjusted COVID-19-related death among Hispanic compared to non-Hispanic Whites [2], whereas a recent meta-analysis of data from observational studies predominantly conducted within a single health care system suggests that there is no disparity in COVID-19 case fatality by ethnicity [3]. However, these studies were not focused on critically ill patients. Therefore, we conducted a study to evaluate ethnic disparities in mortality among critically ill adults with COVID-19 enrolled in the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID).

The design and methods of STOP-COVID have been previously published [4]. STOP-COVID enrolled 4422 consecutive adults (age ≥18 years) with laboratory-confirmed COVID-19 (detected by nasopharyngeal or oropharyngeal swab) admitted to intensive care units (ICU) at 67 U.S. hospitals (S1 Table) between March 4 and May 9, 2020. Of those, 994 (22.6%) were identified by manual review of electronic medical records as Hispanic; 1159 (26.3%) as non-Hispanic White; 1220 (27.7%) as non-Hispanic Black; 288 (6.5%) as Asian or another race; 543 (12.3%) had unknown/not reported race; and 203 (4.6%) had unknown/not reported ethnicity. For the current study, we included STOP-COVID participants who were identified as Hispanic (n = 996) or non-Hispanic White (n = 1159). Patients were followed until the first of hospital discharge, death, or June 5, 2020. The study was approved by the Institutional Review Board (IRB) of the STOP-COVID Coordinating Center (Mass General Brigham IRB), as well as the IRB of each of the 67 participating institutions with a waiver of informed consent.

Study personnel at each site collected data by manual review of electronic medical records using a standardized case report form [4] to enter data into REDCap (Research Electronic Data Capture), a secure online data collection tool [5]. Patient-level data included baseline demographics (sex [men or women], ethnicity [Hispanic or Latino, not Hispanic or Latino, or unknown/not reported], race [White, Black or African American, Asian, American Indian/Alaska Native, Native Hawaiian or Other Pacific Islander, more than one race, or unknown/not reported]), coexisting medical conditions (including diabetes mellitus, hypertension, chronic obstructive pulmonary disease [COPD], asthma, chronic kidney disease [CKD]), symptoms and medications prior to hospital admission, and vital signs on ICU admission. The definitions of baseline characteristics, comorbidities, treatments, and outcomes are presented in S2 Table. In addition, daily data for the 14 days following ICU admission were collected on physiologic and laboratory values, pharmacologic and non-pharmacologic treatments, and organ support.

The primary outcome was mortality within 28 days of ICU admission. Patients who were discharged from the hospital prior to 28 days were considered to be alive (we confirmed the validity of this assumption in a subset of patients, as described elsewhere) [4].

A total of 2153 patients were included (median [IQR] age, 62 [51–71] years; 1462 [67.9%] men; 994 [46.2%] Hispanic and 1159 [53.8%] non-Hispanic White). Baseline characteristics are shown in Table 1.

Compared with non-Hispanic White patients, Hispanic patients were younger (median [IQR] age 56 [46–67] vs. 66 [57–74] years), had lower prevalence of most major comorbid conditions, and were more likely to have markers of severe illness (Table 1). During a median follow-up of 14 days (IQR, 7–24), 785 patients (36.5%) died (356 [35.8%] Hispanic and 429 [37.0%] non-Hispanic White). Twenty-eight day mortality rate was higher among Hispanic patients compared with non-Hispanic White patients for each age strata (Fig 1). Mortality rates by sex, comorbid conditions, and body mass index are shown in Fig 1. In fully-adjusted models, Hispanic patients had higher odds of death compared with non-Hispanic White patients (OR, 1.44; 95% CI, 1.12–1.84). The corresponding OR and 95% CI for each covariate included in the logistic regression model for death at 28 days are shown in S3 Table. Cox proportional regression analyses yielded similar results (multivariable-adjusted HR 1.27, 95% CI 1.08–1.51).

Fig 1. Unadjusted mortality rate by ethnicity, and pre-specified subgroups.

Twenty-eight-day mortality by (a) age group, (b) sex, (c) comorbidities, and (d) body mass index. Abbreviations: CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; DM, diabetes; HTN, hypertension.

https://doi.org/10.1371/journal.pone.0268022.g001

Based on registry data, the COVID-19 mortality rate among Hispanic persons in higher than in non-Hispanic White persons [2, 3]. In contrast, clinical studies have shown no significant difference in mortality between Hispanic and non-Hispanic White patients who tested positive for COVID-19 [12, 13], or among those who were hospitalized with COVID-19 [3, 14–16]. In our study, we observed that among critically ill patients with COVID-19, Hispanic patients were at higher risk of death than non-Hispanic White patients. Reasons for our findings are unclear, but are likely complex and multifactorial. In the general U.S. population, the risk of mortality among Hispanic persons is lower than in non-Hispanic White persons [17], despite the limited access to quality health care, and the high comorbidity burden among Hispanic adults. This phenomenon is often referred to as the “Hispanic paradox”, and has been attributed to strong social support and other favorable social and behavioral factors [18, 19]. The Hispanic survival advantage was not observed in our study of critically ill adults with COVID-19. Potential underlying causes of this striking health disparity include social determinants of health, racism and discrimination, economic disadvantages and, access to quality health care [20–22]. This constellation of adverse factors are known to influence COVID-19 exposure and severity of clinical course. For example, living in crowded conditions and holding jobs that require the use of public transportation, as is often the case among Hispanic adults, is associated with exposure to higher levels of SARS-CoV-2. This is important because higher viral loads have been associated with disease severity and increased mortality [23]. Furthermore, although all patients in our study had access to intensive care, the duration of symptoms prior to ICU admission was significantly longer among Hispanic compared with non-Hispanic White patients (8.6 vs. 7.7 days), suggesting a delay in severe disease recognition, limited access to health care, or other unmeasured factors. In our analysis, the higher mortality risk among Hispanic patients persisted despite adjusting for this and other important factors, but whether other disparities in the timing and quality of care played a role remains unclear. Of note, we did not observe significant differences in the use of remdesivir, corticosteroids and tocilizumab between Hispanic and non-Hispanic White patients. However, our study was conducted early on during the pandemic, before therapies for COVID-19 were widely studied and/or available. Therefore, we were not able to fully evaluate the impact of inequitable use of effective medications, such as monoclonal antibodies [24], on ethnicity-related differences in mortality.