key: cord-0873861-eq9y9db3
authors: Chang, Timothy S.; Ding, Yi; Freund, Malika K.; Johnson, Ruth; Schwarz, Tommer; Yabu, Julie M.; Hazlett, Chad; Chiang, Jeffrey N.; Wulf, David A.; Geschwind, Daniel H.; Butte, Manish J.; Pasaniuc, Bogdan
title: Pre-existing conditions in Hispanics/Latinxs that are COVID-19 risk factors
date: 2021-02-12
journal: iScience
DOI: 10.1016/j.isci.2021.102188
sha: 5fbb4235a8be64653b01c2abecd28e10a7aa0858
doc_id: 873861
cord_uid: eq9y9db3

Coronavirus disease 2019 (COVID-19) has exposed health care disparities in minority groups including Hispanics/Latinxs (HL). Studies of COVID-19 risk factors for HL have relied on county-level data. We investigated COVID-19 risk factors in HL using individual-level, electronic health records in a Los Angeles health system between March 9 and August 31, 2020. Of 9,287 HL tested for SARS-CoV-2, 562 were positive. HL constituted an increasing percentage of all COVID-19 positive individuals as disease severity escalated. Multiple risk factors identified in Non-Hispanic/Latinx whites (NHL-W), like renal disease, also conveyed risk in HL. Pre-existing nonrheumatic mitral valve disorder was a risk factor to HL hospitalization but not for NHL-W COVID-19 or HL influenza hospitalization, suggesting it may be a specific HL COVID-19 risk. Admission laboratory values also suggested that HL presented with a greater inflammatory response. COVID-19 risk factors for HL can help guide equitable government policies and identify at-risk populations.

as well (Cheng et al., 2019; Rodriguez-Diaz et al., 2020; US Department of Health and Human Services, 2018) .

There are limited studies investigating HL characteristics for COVID-19 diagnosis and severe outcomes using individual level data. In a Providence, Rhode Island study of HL with COVID-19, 75% were less than 50 years old (Weng et al., 2020) . In Baltimore, Maryland, hospitalized HL individuals were younger and had lower rates of comorbidities (hypertension, congestive heart failure, chronic obstructive pulmonary disease) compared to hospitalized non-HL white individuals (Martinez et al., 2020) . No previous study using individual level data has investigated the risk factors for COVID-19 diagnosis, inpatient admission, or severe outcome in HL individuals.

In this retrospective study, we aimed to first validate the extendibility of known risk factors for COVID-19 and to determine whether there were pre-existing risk factors observed in HL, but not NHL-W for COVID-19 diagnosis susceptibility, inpatient admission, and severe outcome. We leveraged individual, patient-level, de-identified electronic health record data from the University of California Los Angeles (UCLA) Health System, a single homogenous medical system. Although many previously identified risk factors were observed in both HL and NHL-W, we identified COVID-19 risk factors that were observed in HL, but not NHL-W. Individuals with numerous pre-existing conditions may be in a general state of poor health, conferring a high risk of hospitalization for any infection, not just COVID-19. To test the hypothesis that certain preexisting conditions offer a specific risk for COVID-19, we determined if inpatient risk factors for COVID-19 were also inpatient risk factors for influenza.

J o u r n a l P r e -p r o o f 6

The UCLA Health System includes two hospitals (520 and 281 inpatient beds) and 210 primary and specialty outpatient locations predominantly within Los Angeles County. We leveraged an extract of the de-identified electronic health records from the UCLA Health System known as the Data Discovery Repository, which contains longitudinal records for more than 1.5 million patients since 2013.

This retrospective analysis included individuals who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via reverse transcriptase polymerase chain reaction (RT-PCR) within the UCLA Health System between March 9, 2020, and August 31, 2020 . Of the 58,901 individuals PCR-tested for SARS-CoV-2 (Tested) meeting inclusion/exclusion criteria (Methods), 1,994 were COVID-19 positive (3.3% of Tested), 342 were admitted in the hospital (Inpatient) (17% of COVID-19 positive) and 74 were treated in the intensive care unit or required intubation (Severe) (3.7% of COVID-19 positive) (Figure 1 ).

To determine pre-existing conditions and medications associated with COVID-19 outcome in Hispanics/Latinxs (HL), we included HL individuals self-identifying as HL ethnicity and any race. We included all race groups, not only white, as many HL individuals self-identify as "other race" (52% of HL COVID-19 Tested). We analyzed diagnoses entered in the EHR prior to an individual's SARS-CoV-2 test. International Statistical Classification of Diseases (ICD) codes were mapped to ~1,800 phecodes, which have been shown to represent meaningful and interpretable phenotypes (Wei et al., 2017) . We compared risk factors in HL to COVID-19 outcome risk factors in Non-Hispanic/Latinx whites (NHL-W), which has been the study population for many previous analyses (Argenziano et al., 2020; Goyal et al., 2020; Grasselli et al., 2020a; Hirsch et al., 2020; Lighter et al., 2020; Williamson et al., 2020) , Table S1 ), many of which are known to disproportionately affect HL individuals (Dominguez et al., 2015; Velasco-Mondragon et al., 2016) . After correction for these known risk factors, the odds ratio for having a positive test remained >2.5 in HL, and for being hospitalized remained >2.5 in HL (Table 2, Table S2 ). These findings support the hypothesis of HL-specific risk factors (medical and/or socioeconomic) that increase risk of having COVID-19 disease and being hospitalized (Ong et al., 2020) .

COVID-19 risk factors (coronary heart disease, congestive heart failure, chronic obstructive pulmonary disease, type 2 diabetes, hyperlipidemia, hypertension, obesity, and chronic renal disease (Goyal et al., 2020; Grasselli et al., 2020a Grasselli et al., , 2020b Guan et al., 2020; Gupta et al., 2020; Li et al., 2020; Yang et al., 2020a; Zhou et al., 2020a; Zhu et al., 2020) ) have been previously identified primarily from COVID-19 inpatient cohorts and white or Asian populations. By grouping phecodes into these known risk factor categories (Table S1), we determined if these were also risk factors in HL while controlling for age and sex. For COVID-19 diagnosis susceptibility, none of these known risk factors were significant in HL. In NHL-W, To identify additional pre-existing conditions aside from known risk factors that may be COVID-19 susceptibility risk factors in HL, we evaluated all phecodes while controlling for age and sex. In HL, we did not identify any additional phecodes associated with COVID-19 diagnosis susceptibility after multiple testing correction (Methods). In contrast for NHL-W, J o u r n a l P r e -p r o o f 9 dementia (OR 4.1 [2.7-6.1], p=3.4 x 10 -9 ), diastolic heart failure (OR 3.0 [1.9-4.4], p=5.2 x 10 -6 ), and fever of unknown origin (OR 2.0 [1.6-2.4], p=1.3 x 10 -10 ) were pre-existing susceptibility risk factors ( Figure S1 , Table S3 ). Of these NHL-W risk factors, dementia was nominally significant and had a similar effect size in HL (OR 3.7 [1.8-7.0], p=8.3 x 10 -4 ). This suggests dementia was a shared risk factor in NHL-W and HL for testing COVID-19 positive. We did not identify an age or sex specific interaction for these significant phecodes in NHL-W.

We also evaluated if any of the NHL-W risk factor effects were significantly different than the HL risk factor effects by modeling the interaction term of ethnicity (HL vs NHL-W) and the phecode (Methods). The COVID-19 susceptibility odds ratio increased by 1.5 [95% CI 1.1-2.0] (p=0.004) if individuals were NHL-W and exhibited pre-existing fever of unknown origin compared to individuals who were HL and had pre-existing fever of unknown origin.

To determine if the risk factors were not correlated with and not already explained by previously identified COVID-19 risk factors as above (coronary heart disease, congestive heart failure, chronic obstructive pulmonary disease, type 2 diabetes, hyperlipidemia, hypertension, obesity, and chronic renal disease (Goyal et al., 2020; Grasselli et al., 2020a; Guan et al., 2020; Li et al., 2020; Yang et al., 2020a; Zhou et al., 2020a; Zhu et al., 2020) ) (Table S1, Methods), we controlled for these in our model in addition to age and sex. For NHL-W, all pre-existing susceptibility risk factors including fever of unknown origin (OR 2.0 [1.6-2.4], p=1.7 x 10 -10 ) remained significant after controlling for these known risk factors (Table S4 ). This result showed that fever of unknown origin, which could occur in cancer, occult infections, and inflammatory conditions (Roth and Basello, 2003) , was a risk factor for COVID-19 positive testing in NHL-W independent of previously identified risk factors, and not observed as a risk factor in HL.

Of the known COVID-19 risk factors, chronic kidney disease (OR 4.9 [2.7, 8.9 ], p=2.1 x 10 -7 ), hypertension (OR 3.2 [2.0, 5.1], p=3.0 x 10 -6 ), congestive heart failure (OR 5.5 [2.2, 15], p=2.5 x J o u r n a l P r e -p r o o f 10 10 -4 ), diabetes (2.1 [1.2, 3.5], p=0.007), and coronary heart disease (OR 2.5 [1.2, 4.9], p=0.01) were significant risk factors for hospitalization in HL. Chronic kidney disease (OR 2.7 [1.4, 5 .1], p=0.003), congestive heart failure (OR 2.8 [1.4, 5.8], p=0.004), and coronary heart disease (OR 1.9 [1.1, 3.5], p=0.03) were also significant risk factors for hospitalization in NHL-W.

When evaluating additional phecodes that may be pre-existing risk factors for hospitalization in HL, we found nonrheumatic mitral valve disorder , p=1.1 x 10 - Table S5 ).

For these significant inpatient admission risk phecodes in HL and NHL-W, we found that only kidney transplant had a significant age > 65 years interaction in HL for inpatient admission.

Although age > 65 years (11) (12) (13) (14) (15) (16) (17) (18) (19) , p=2.2x10 -22 ) and kidney transplant (OR 9.4 [4.1-23], p<2.4x10 -7 ) individually increased inpatient admission risk, being both > 65 years old and a kidney transplant recipient decreased this risk (OR 0.02 [1.4x10 -4 -0.50], p=0.02). We did not identify a sex specific interaction for these significant phecodes in HL and NHL-W.

The risk factor effects of nonrheumatic mitral valve disorder and hypertension for HL was significantly increased compared to their risk factor effects in NHL-W. The inpatient odds ratio significantly associated with inpatient admission suggesting they were not correlated with or already explained by previously identified COVID-19 risk factors (Table S6) .

We determined if these COVID-19 inpatient risk factors observed in HL, but not NHL-W were also observed in another viral infection, influenza. Similar to COVID-19, HL ethnicity increased the risk of inpatient admission for individuals with influenza (OR 2.8 [2.1-4.0], p=2.2 x 10 -10 ) and remained significantly elevated when correcting for known risk factors (OR 2.4 [1.7-3.4], p=3.9 x 10 -7 ). In contrast to the observations in COVID-19 positive inpatients, nonrheumatic mitral valve disorder was not a pre-existing risk factor for hospitalization due to influenza for either HL or NHL-W individuals ( Figure S2 , Table S7 ).

As with COVID-19, hypertension was a significant pre-existing risk factor for hospitalization due to influenza in HL individuals ], p=1.4 x 10 -6 ), but not in NHL-W individuals ( Figure S2 , Table S7 ). Pre-existing renal disorders also conferred a similar risk of hospitalization for COVID-19 as they did for influenza in HL and NHL-W. Severe renal disorders including end stage renal disease , p=1.4 x 10 -11 ) and renal dialysis (OR 24 [9.1, 72], p=1.3 x 10 -10 ) remained risk factors for hospitalization due to influenza only for HL individuals. Acute renal failure was a risk factor for hospitalization due to influenza for HL (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) , p=7.8 x 10 -16 ) and NHL-W (OR 8.5 [4.6-15], p=5.8 x 10 -11 ) ( Figure S2 , Table S7 ).

Of the known COVID-19 risk factors, hyperlipidemia was protective in HL for the COVID-19 positive inpatient severe outcome (OR 0.26 [0.08-0.71], p=0.008) (Figure 2 ). This finding was not observed in NHL-W. We did not identify any additional phecodes significantly associated with the COVID-19 Severe group, although our power was low (N=35 HL, N=19 NHL-W COVID-19 positive with severe outcome) compared to the COVID-19 Inpatient group (N=132 HL, N=125 NHL-W).

One potential explanation for worse COVID-19 outcomes in HL could be that HL individuals presented to the health system with more severe disease. We therefore sought to determine if HL COVID-19 positive inpatient disease severity was reflected in more abnormal vital signs or laboratory values compared to NHL-W individuals. Controlling for age, sex, and known risk factors (Table S1 ), we analyzed vitals and labs +/-one day of inpatient admission date. White blood cell count (mean 7.93 ± standard deviation 4.2 x10 3 /µL HL vs 6.85 ± 4.0 x10 3 /µL NHL-W, p=0.046), platelet count (216 ± 91 x10 3 /µL HL vs 187 ± 93 x10 3 /µL NHL-W, p=0.023), creatinine (1.8 ± 2.7 mg/dL HL vs 1.3 ± 0.9 mg/dL NHL-W, p=0.045) and C-reactive protein (9.0 ± 6.4 mg/dL HL vs 7.6 ± 6.5 mg/dL NHL-W, p=0.011) were higher in HL COVID-19 positive inpatients compared to NHL-W COVID-19 positive inpatients (Table 3) . This suggests hospitalized HL presented with a greater inflammatory response consistent with more advanced disease compared to hospitalized NHL-W.

Next, we identified HL individuals that were outliers based on what would be an expected COVID-19 clinical course predicated on their major predictive factors, namely age and pre-existing conditions. These outlier groups included: 1) individuals that were young with no major comorbidities (18-35 years old), but who were hospitalized, and 2) older individuals with J o u r n a l P r e -p r o o f 13 high risk for a serious COVID-19 clinical course (>70 years old with at least three of the known risk factors), but who were not hospitalized. These individuals may represent extremes of COVID-19 susceptibility and resistance, and therefore may carry genetic immunological susceptibilities or resistances to infection (Blanco-Melo et al., 2020; COVID-19 Host Genetics Initiative, 2020; Ellinghaus et al., 2020; Nguyen et al., 2020) . 

Controversy remains over the protective or detrimental effects of medication classes including angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) (Mancia et al., 2020; Reynolds et al., 2020; Zhang et al., 2020c) , immunosuppressants (D'Antiga, 2020; Mehta et al., 2020; Monti et al., 2020; Novi et al., 2020; Ritchie and Singanayagam, 2020) , steroids (Shang et al., 2020; Zha et al., 2020) , anticoagulants Thachil, 2020; Thachil et al., 2020) , and non-steroidal anti-inflammatory drugs (Little, 2020) . We investigated whether the prescription of these medications 90 days prior to SARS-CoV-2 testing (See Table S8 for drugs assigned to each medication class) was associated with admitted to the hospital, or having a severe course, as previously reported (Reynolds et al., 2020) (Table 4, Table S9 ).

Previous studies have not investigated the association of medication duration with COVID-19 outcomes as has been performed in influenza where longer ACEI and ARB usage was protective for influenza incidence (Chung et al., 2020) . In our study, comparing medication prescription of < 1 year to no prescription and medication prescription of ≥ 1 year to no prescription, did not show an association of ACEI or ARBs with COVID-19 inpatient admission risk in HL or NHL-W ( Figure S3 ). For HL, immunosuppressant prescription < 1 year and ≥ 1 year compared to no prescription remained a risk factor for inpatient admission (<1 year OR 6.7 [1.6-31], p=0.008; ≥ 1 year OR 4.2 [1.6-11], p=0.004). Steroid prescription was only associated with increased inpatient admission risk for HL if prescribed less than one year compared to no prescription (<1 year OR 5.8 [1.7-20], p=0.005) ( Figure S3 ).

Identifying COVID-19 risk factors can inform patient care, public policies, and future research aimed at improving outcomes and reducing health care disparities. We leveraged our ability to query de-identified electronic health records to determine COVID-19 risk factors for HL in the UCLA Health System. Our analysis at the individual, patient-level successfully captured the results of previously reported risk factors for more severe COVID-19 disease, such as chronic renal disease, diabetes, and hypertension across ethnicities (Goyal et al., 2020; Grasselli et al., 2020a Grasselli et al., , 2020b Guan et al., 2020; Gupta et al., 2020; Li et al., 2020; Yang et al., 2020a; Zhu et al., 2020) , validating our EHR-based approach. Our analysis at the individual, patient-level also successfully captured the results of previously reported health disparities in HL individuals that were identified at the aggregate level (Chicago Department of Public Health, 2020; Los Angeles County Department of Public Health, Chief Science Office, 2020; New York City Health, 2020; Rodriguez-Diaz et al., 2020) . Moreover, we identified risk factors for COVID-19 inpatient admission, some of which were specific to HL and not observed as risk factors in NHL-W.

Having pre-existing nonrheumatic mitral valve disorder was a HL risk factor for hospitalization, but this condition was not observed as a risk factor in NHL-W. Nonrheumatic mitral valve disorder has not been previously reported to be a COVID-19 risk factor, possibly because it has not been evaluated in the HL population. Nonrheumatic mitral valve disorder was not correlated with known risk factors such as coronary heart disease and was specific to COVID-19, as it was not an influenza inpatient risk factor in HL individuals. Previous studies investigating influenza inpatient admission risk factors did not identify mitral valve disorders either (Ono et al., 2016; Puig-Barberà et al., 2016) . It is possible that symptoms of mitral valve disorders such as underlying dyspnea may exacerbate COVID-19 symptoms leading to an J o u r n a l P r e -p r o o f 16 increased risk of inpatient admission. Further studies are necessary to validate this risk factor and determine the mechanism of association.

Significant risk factors for becoming critically ill (intensive care unit admission or death) among hospitalized COVID-19 patients include hypertension, renal disease (chronic renal disease, acute kidney injury), cardiac disease (cardiac injury, coronary artery disease), pulmonary disease (chronic obstructive pulmonary disease, acute respiratory distress syndrome), diabetes, hyperlipidemia, and obesity (Argenziano et al., 2020; Hirsch et al., 2020; Huang et al., 2020; Li et al., 2020; Lighter et al., 2020; Wang et al., 2020b; Williamson et al., 2020; Zhou et al., 2020a) . These analyses were performed in China, Italy, United Kingdom and United States, and not sub-grouped by ethnicity if applicable. Many of these risk factors including chronic kidney disease, hypertension, congestive heart failure, diabetes and coronary heart disease were HL risk factors for inpatient admission. Additional renal disorders such as acute renal failure, end stage renal disease, and renal dialysis were risk factors for hospitalization in HL individuals and were also risk factors in NHL-W individuals. Hypertension, on the other hand, was a much stronger risk factor for hospitalization in HL than in NHL-W. For COVID-19 severe outcomes in our study, hyperlipidemia decreased risk in HL. Previous studies have been mixed on cholesterol risk in COVID-19 as hyperlipidemia increased risk for mortality among ICU patients (Grasselli et al., 2020b) , but lower cholesterol levels were associated with COVID-19 inpatient severity (Wei et al., 2020) . Lastly, reduced vitamin D has been variably associated with worse COVID-19 outcomes and a pilot clinical trial of vitamin D treatment showed improved outcomes (Entrenas Castillo et al., 2020; Ilie et al., 2020; Jain et al., 2020; Rhodes et al., 2020) . However, we did not find an association of pre-existing vitamin D insufficiency with any COVID-19 outcomes.

The risk of inpatient admission for HL compared to NHL-W remained elevated even when controlling for multiple comorbidities. One contributing explanation could be that HL patients present initially with more advanced disease. To address this objectively, we compared J o u r n a l P r e -p r o o f whether presenting vital signs or laboratory values were more severe for HL inpatients than NHL-W inpatients. While vital signs were similar in both groups, we found that HL had higher white blood cell counts, platelets, creatinine and C-reactive protein, all potential inflammatory and acute phase reactants consistent with more advanced disease (Ayalew Tefferi, 2020; Irving Kushner, 2020) . Previous studies have shown leukocytosis, elevated creatinine, and elevated C-reactive protein were associated with a severe COVID-19 outcome among hospitalized patients (Ali et al., 2020; Cheng et al., 2020; Li et al., 2020; Zhang et al., 2020a Zhang et al., , 2020b . Thrombocytopenia, rather than thrombocytosis, during hospitalization was a risk factor for severe COVID-19 outcome (Goyal et al., 2020; Guan et al., 2020; Huang et al., 2020; Lippi et al., 2020; Yang et al., 2020b) .

There has been concern that some individuals with COVID-19 have an exaggerated immune response resulting in cytokine storm or secondary haemophagocytic lymphohistiocytosis, and studies have suggested that short-term immunosuppression is warranted (Mehta et al., 2020; Ritchie and Singanayagam, 2020; Zhou et al., 2020b) . Previous studies investigated small numbers of COVID-19 positive individuals (<4) on immunosuppression prior to COVID-19 diagnosis, finding that these individuals in general did well and did not have a severe outcome (D'Antiga, 2020; Monti et al., 2020; Novi et al., 2020) .

Here we analyzed 150 individuals on either oral steroids or other immunosuppressants. Both HL and NHL-W individuals on oral steroids or immunosuppressants had an increased risk of inpatient admission. These medications did not increase the risk of an inpatient severe outcome, although the Severe analysis group had less power. The explanation for increased risk of inpatient admission may be biological or due to clinician bias. Immunosuppressed COVID-19 individuals may have more severe symptoms requiring inpatient admission.

Clinicians may also have a lower threshold of inpatient admission for patients on immunosuppressive medication. We did not assess whether immunosuppressive medication J o u r n a l P r e -p r o o f 18 was stopped, continued or changed on admission, and therefore, we are unable to draw conclusions on whether to adjust immunosuppression in COVID-19 hospitalized patients.

Recognizing COVID-19 risk factors can encourage individuals with these risk factors to take appropriate precautions, understand how pre-morbid conditions may affect COVID-19 disease, anticipate necessary medical treatment, and possibly reduce risk by managing these conditions (CDC, 2020) . Public health measures to promote accurate COVID-19 information for the general population may not be as effective in minority populations. In Pennsylvania, the Center for Disease Control and Prevention's (CDC) Racial and Ethnic Approaches to Community Health (REACH) program engaged HL community leaders and learned the community had difficulty accessing reliable information in Spanish (Calo et al., 2020) . As such This study identifies risk factors for COVID-19 inpatient admission that are specific to HL and others that were shared with NHL-W. These risk factors should spur future work in understanding the mechanistic underpinnings of these observations and implementing equitable strategies to mitigate these risk factors.

Additional explanations for the increased HL inpatient admission risk compared to NHL-W may be environmental such as air pollution (Brandt et al., 2020) , socioeconomic such as access to health care (Chowkwanyun and Reed, 2020; Ong et al., 2020) , delay from symptom onset to health care presentation (Chowell et al., 2012) , and genetic suseceptbility (COVID-19 Host Genetics Initiative, 2020; Kuo et al., 2020) . These additional covariates were not available in our de-identified EHR dataset. Geographical location like zip codes was not available to link environmental exposures such as air pollution Zoran et al., 2020) or temperatures (Poirier et al., 2020) . We also did not have data regarding socioeconomic factors such as income or health insurance, which has been used as a proxy for socioeconomic status in other studies (Casey et al., 2018) . We did not analyze data from the fall and winter seasons of 2020 as the study period was from March 9, 2020 to August 31, 2020. We did not investigate all self-identified minority race groups such as African Americans. The sample size of African Americans with COVID-19 was 70% less than Hispanics/Latinx with only 10 African Americans with a severe outcome. Focusing on other minority groups, longer study periods, environmental factors and socioeconomic factors are areas of future work to be pursued.

Requests for additional information can be directed to the Lead Contacts: Timothy S Chang, (timothychang@mednet.ucla.edu); Manish J Butte, (mbutte@mednet.ucla.edu); Bogdan Pasaniuc, (bpasaniuc@mednet.ucla.edu)

This study did not generate unique reagents

Individual electronic health record data are not publicly availability due to patient confidentiality and security concerns. Collaboration with the study authors who have been approved by UCLA Table S3, Table S4, Table S5, Table S6, Table S7 . Significant pre-existing condition risk factors for COVID-19 inpatient admission correcting for age and sex grouped by phecode category. Hispanics/Latinxs (blue) and Non-Hispanic/Latinx whites (purple). 95% confidence intervals for odds ratios are shown. Solid lines indicate risk factors that are Bonferroni significant. Dotted lines are not Bonferroni significant. inf = infectious, heme = hematopoietic, Bonf = Bonferroni Tables   Table 1: Table 4 . Related to Figure S3 , J o u r n a l P r e -p r o o f

Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series

Approach to the patient with thrombocytosis

Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Air pollution, racial disparities, and COVID-19 mortality

Reaching the Hispanic Community About COVID-19 Through Existing Chronic Disease Prevention Programs

Measures of SES for Electronic Health Record-based Research

Coronavirus Disease

CDC Activities and Initiatives Supporting the COVID-19 Response and the President's Plan for Opening America Up Again

Kidney disease is associated with in-hospital death of patients with COVID-19

Prevalence of Diabetes by Race and Ethnicity in the United States

Chicago Latest COVID-19 Data

Epidemiological characteristics and underlying risk factors for mortality during the autumn 2009 pandemic wave in Mexico

Racial Health Disparities and Covid-19 -Caution and Context

Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom

The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic

Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic

Vital Signs: Leading Causes of Death, Prevalence of Diseases and Risk Factors, and Use of Health Services Among Hispanics in the United States -2009-2013

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study

Clinical Characteristics of Covid-19 in

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region

Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in

Clinical Characteristics of Coronavirus Disease 2019 in China

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Acute kidney injury in patients hospitalized with COVID-19

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality

Acute phase reactants

Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers

APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort

Home -Latino Coalition for a Healthy California

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission

Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis

Non-steroidal anti-inflammatory drugs and covid-19

COVID-19 Media Page -LA County Department of Public Health

Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19

SARS-CoV-2 Positivity Rate for Latinos in the

COVID-19: consider cytokine storm syndromes and immunosuppression

Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies

Age-adjusted rates of lab confirmed COVID-19

Human leukocyte antigen susceptibility map for SARS-CoV-2

COVID-19 in a MS patient treated with ocrelizumab: does immunosuppression have a protective role?

Struggling to Stay Home: How COVID-19 Shelter in Place Policies Affect Los Angeles County's Black and Latino Neighborhoods (UCLA Latino Policy and Politics Initiative, the UCLA Center for Neighborhood Knowledge

Factors associated with hospitalization for seasonal influenza in a Japanese nonelderly cohort

The role of environmental factors on transmission rates of the COVID-19 outbreak: an initial assessment in two spatial scales

Epidemiology of Hospital Admissions with Influenza during the 2013/2014 Northern Hemisphere Influenza Season: Results from the Global Influenza Hospital Surveillance Network

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19

Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity

Immunosuppression for hyperinflammation in COVID-19: a double-edged sword?

Risk for COVID-19 infection and death among Latinos in the United States: Examining heterogeneity in transmission dynamics

Approach to the adult patient with fever of unknown origin

On the use of corticosteroids for 2019-nCoV pneumonia

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

The versatile heparin in COVID-19

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

Sustaining containment of COVID-19 in China

Labor force characteristics by race and ethnicity

Hispanic health in the USA: a scoping review of the literature

Airborne particulate matter, population mobility and COVID-19: a multi-city study in China

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in

Evaluating phecodes, clinical classification software, and ICD-9-CM codes for phenome-wide association studies in the electronic health record

Hypolipidemia is associated with the severity of COVID-19

Characteristics and clinical outcomes of COVID-19 in Hispanic/Latino patients in a community setting: A retrospective cohort study

Factors associated with COVID-19-related death using OpenSAFELY

Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: A systematic review and meta-analysis

Thrombocytopenia and its association with mortality in patients with COVID-19

Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19)

Clinical, radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients

Risk Factors of Severe Disease and Efficacy of Treatment in Patients Infected with COVID-19: A Systematic Review, Meta-Analysis and Meta-Regression Analysis

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Short-Term Moderate-Dose Corticosteroid Plus Immunoglobulin Effectively Reverses COVID-19 Patients Who Have Failed Low-Dose Therapy

Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes

Assessing the relationship between surface levels of PM2.5 and PM10 particulate matter impact on COVID-19 in

Hispanic/Latinx COVID-19 positive Inpatient vs Outpatient Non-Hispanic/Latinx white COVID-19 positive Inpatient vs Outpatient Severe Hispanic/Latinx COVID-19 positive Inpatient Severe vs Not Severe on-Hispanic/Latinx white COVID-19 positive Inpatient Severe vs Not Severe 56,907 COVID-19 negative 8,725 Hispanic/Latinx 28,885 Non-Hispanic/Latinx white 1,652 Outpatient 430 Hispanic/Latinx 554 Non-Hispanic

Hispanic/Latinx 106 Non-Hispanic/Latinx white Excluded 18,369 unknown results 365 missing age or sex 5,046 no encounter prior to SARS-CoV-2 test 58,901 SARS-CoV-2 PCR Tested Included in Analyses 9

The authors declare no competing interests J o u r n a l P r e -p r o o f