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Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19

Nln, Ilona; Fernandez-Ruiz, Ruth; Muskardin, Theresa L Wampler; Paredes, Jacqueline L; Blazer, Ashira D; Tuminello, Stephanie; Attur, Mukundan; Iturrate, Eduardo; Petrilli, Christopher M; Abramson, Steven B; Chakravarti, Aravinda; Niewold, Timothy B
Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity. BACKGROUND: We find that a number of IFN pathway lupus risk alleles significantly impact mortality following COVID-19 infection. These data support the idea that type I IFN pathway risk alleles for autoimmune disease may persist in high frequency in modern human populations due to a benefit in our defense against viral infections. TRANSLATIONAL SIGNIFICANCE: We develop multivariate prediction models which combine genetics and known biomarkers of severity to result in greatly improved prediction of mortality in acute COVID-19. The specific associated alleles provide some clues about key points in our defense against COVID-19.
PMID: 35114420
ISSN: 1878-1810
CID: 5153812

Clinical and genomic signatures of rising SARS-CoV-2 Delta breakthrough infections in New York

Duerr, Ralf; Dimartino, Dacia; Marier, Christian; Zappile, Paul; Levine, Samuel; François, Fritz; Iturrate, Eduardo; Wang, Guiqing; Dittmann, Meike; Lighter, Jennifer; Elbel, Brian; Troxel, Andrea B; Goldfeld, Keith S; Heguy, Adriana
In 2021, Delta has become the predominant SARS-CoV-2 variant worldwide. While vaccines effectively prevent COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occur. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contribute to increased rates of breakthrough infections compared to unvaccinated controls. Here, we show a steep and near complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25, its spike mutation S112L, and nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthroughs increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. Our data indicate a limited impact of vaccine escape in favor of Delta's increased epidemic growth in times of waning vaccine protection.
PMID: 34909779
ISSN: n/a
CID: 5085062

Predicting inpatient pharmacy order interventions using provider action data

Balestra, Martina; Chen, Ji; Iturrate, Eduardo; Aphinyanaphongs, Yindalon; Nov, Oded
Objective/UNASSIGNED:The widespread deployment of electronic health records (EHRs) has introduced new sources of error and inefficiencies to the process of ordering medications in the hospital setting. Existing work identifies orders that require pharmacy intervention by comparing them to a patient's medical records. In this work, we develop a machine learning model for identifying medication orders requiring intervention using only provider behavior and other contextual features that may reflect these new sources of inefficiencies. Materials and Methods/UNASSIGNED:Data on providers' actions in the EHR system and pharmacy orders were collected over a 2-week period in a major metropolitan hospital system. A classification model was then built to identify orders requiring pharmacist intervention. We tune the model to the context in which it would be deployed and evaluate global and local feature importance. Results/UNASSIGNED:The resultant model had an area under the receiver-operator characteristic curve of 0.91 and an area under the precision-recall curve of 0.44. Conclusions/UNASSIGNED:Providers' actions can serve as useful predictors in identifying medication orders that require pharmacy intervention. Careful model tuning for the clinical context in which the model is deployed can help to create an effective tool for improving health outcomes without using sensitive patient data.
PMID: 34617009
ISSN: 2574-2531
CID: 5092072

Assessment of Racial/Ethnic Disparities in Hospitalization and Mortality in Patients With COVID-19 in New York City

Ogedegbe, Gbenga; Ravenell, Joseph; Adhikari, Samrachana; Butler, Mark; Cook, Tiffany; Francois, Fritz; Iturrate, Eduardo; Jean-Louis, Girardin; Jones, Simon A; Onakomaiya, Deborah; Petrilli, Christopher M; Pulgarin, Claudia; Regan, Seann; Reynolds, Harmony; Seixas, Azizi; Volpicelli, Frank Michael; Horwitz, Leora Idit
Importance/UNASSIGNED:Black and Hispanic populations have higher rates of coronavirus disease 2019 (COVID-19) hospitalization and mortality than White populations but lower in-hospital case-fatality rates. The extent to which neighborhood characteristics and comorbidity explain these disparities is unclear. Outcomes in Asian American populations have not been explored. Objective/UNASSIGNED:To compare COVID-19 outcomes based on race and ethnicity and assess the association of any disparities with comorbidity and neighborhood characteristics. Design, Setting, and Participants/UNASSIGNED:This retrospective cohort study was conducted within the New York University Langone Health system, which includes over 260 outpatient practices and 4 acute care hospitals. All patients within the system's integrated health record who were tested for severe acute respiratory syndrome coronavirus 2 between March 1, 2020, and April 8, 2020, were identified and followed up through May 13, 2020. Data were analyzed in June 2020. Among 11 547 patients tested, outcomes were compared by race and ethnicity and examined against differences by age, sex, body mass index, comorbidity, insurance type, and neighborhood socioeconomic status. Exposures/UNASSIGNED:Race and ethnicity categorized using self-reported electronic health record data (ie, non-Hispanic White, non-Hispanic Black, Hispanic, Asian, and multiracial/other patients). Main Outcomes and Measures/UNASSIGNED:The likelihood of receiving a positive test, hospitalization, and critical illness (defined as a composite of care in the intensive care unit, use of mechanical ventilation, discharge to hospice, or death). Results/UNASSIGNED:Among 9722 patients (mean [SD] age, 50.7 [17.5] years; 58.8% women), 4843 (49.8%) were positive for COVID-19; 2623 (54.2%) of those were admitted for hospitalization (1047 [39.9%] White, 375 [14.3%] Black, 715 [27.3%] Hispanic, 180 [6.9%] Asian, 207 [7.9%] multiracial/other). In fully adjusted models, Black patients (odds ratio [OR], 1.3; 95% CI, 1.2-1.6) and Hispanic patients (OR, 1.5; 95% CI, 1.3-1.7) were more likely than White patients to test positive. Among those who tested positive, odds of hospitalization were similar among White, Hispanic, and Black patients, but higher among Asian (OR, 1.6, 95% CI, 1.1-2.3) and multiracial patients (OR, 1.4; 95% CI, 1.0-1.9) compared with White patients. Among those hospitalized, Black patients were less likely than White patients to have severe illness (OR, 0.6; 95% CI, 0.4-0.8) and to die or be discharged to hospice (hazard ratio, 0.7; 95% CI, 0.6-0.9). Conclusions and Relevance/UNASSIGNED:In this cohort study of patients in a large health system in New York City, Black and Hispanic patients were more likely, and Asian patients less likely, than White patients to test positive; once hospitalized, Black patients were less likely than White patients to have critical illness or die after adjustment for comorbidity and neighborhood characteristics. This supports the assertion that existing structural determinants pervasive in Black and Hispanic communities may explain the disproportionately higher out-of-hospital deaths due to COVID-19 infections in these populations.
PMID: 33275153
ISSN: 2574-3805
CID: 4694552

RAAS Inhibitors and Risk of Covid-19. Reply [Comment]

Reynolds, Harmony R; Adhikari, Samrachana; Iturrate, Eduardo
PMID: 33108107
ISSN: 1533-4406
CID: 4646512

COVID-19 Pneumonia Hospitalizations Followed by Re-presentation for Presumed Thrombotic Event

Brosnahan, Shari B; Bhatt, Alok; Berger, Jeffery S; Yuriditsky, Eugene; Iturrate, Eduardo; Amoroso, Nancy E
PMID: 32589950
ISSN: 1931-3543
CID: 4493712

Leveraging clinical decision support tools to improve guideline-directed medical therapy in patients with atherosclerotic cardiovascular disease at hospital discharge

Vani, Anish; Kan, Karen; Iturrate, Eduardo; Levy-Lambert, Dina; Smilowitz, Nathaniel R; Saxena, Archana; Radford, Martha J; Gianos, Eugenia
BACKGROUND:Guidelines recommend moderate to high-intensity statins and antithrombotic agents in patients with atherosclerotic cardiovascular disease (ASCVD). However, guideline-directed medical therapy (GDMT) remains suboptimal. METHODS:In this quality initiative, best practice alerts (BPA) in the electronic health record (EHR) were utilized to alert providers to prescribe to GDMT upon hospital discharge in ASCVD patients. Rates of GDMT were compared for 5 months pre- and post-BPA implementation. Multivariable regression was used to identify predictors of GDMT. RESULTS:In 5985 pre- and 5568 post-BPA patients, the average age was 69.1 ± 12.8 years and 58.5% were male. There was a 4.0% increase in statin use from 67.3% to 71.3% and a 3.1% increase in antithrombotic use from 75.3% to 78.4% in the post-BPA cohort. CONCLUSIONS:This simple EHR-based initiative was associated with a modest increase in ASCVD patients being discharged on GDMT. Leveraging clinical decision support tools provides an opportunity to influence provider behavior and improve care for ASCVD patients, and warrants further investigation.
PMID: 32986236
ISSN: 1897-5593
CID: 4616532

Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System

Bilaloglu, Seda; Aphinyanaphongs, Yin; Jones, Simon; Iturrate, Eduardo; Hochman, Judith; Berger, Jeffrey S
PMID: 32702090
ISSN: 1538-3598
CID: 4532682

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

Reynolds, Harmony R; Adhikari, Samrachana; Pulgarin, Claudia; Troxel, Andrea B; Iturrate, Eduardo; Johnson, Stephen B; Hausvater, Anaïs; Newman, Jonathan D; Berger, Jeffrey S; Bangalore, Sripal; Katz, Stuart D; Fishman, Glenn I; Kunichoff, Dennis; Chen, Yu; Ogedegbe, Gbenga; Hochman, Judith S
BACKGROUND:There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS:We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS:Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS:We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
PMID: 32356628
ISSN: 1533-4406
CID: 4412912

Development, Implementation, and Evaluation of a Personalized Machine Learning Algorithm for Clinical Decision Support: Case Study With Shingles Vaccination

Chen, Ji; Chokshi, Sara; Hegde, Roshini; Gonzalez, Javier; Iturrate, Eduardo; Aphinyanaphongs, Yin; Mann, Devin
BACKGROUND:Although clinical decision support (CDS) alerts are effective reminders of best practices, their effectiveness is blunted by clinicians who fail to respond to an overabundance of inappropriate alerts. An electronic health record (EHR)-integrated machine learning (ML) algorithm is a potentially powerful tool to increase the signal-to-noise ratio of CDS alerts and positively impact the clinician's interaction with these alerts in general. OBJECTIVE:This study aimed to describe the development and implementation of an ML-based signal-to-noise optimization system (SmartCDS) to increase the signal of alerts by decreasing the volume of low-value herpes zoster (shingles) vaccination alerts. METHODS:We built and deployed SmartCDS, which builds personalized user activity profiles to suppress shingles vaccination alerts unlikely to yield a clinician's interaction. We extracted all records of shingles alerts from January 2017 to March 2019 from our EHR system, including 327,737 encounters, 780 providers, and 144,438 patients. RESULTS:During the 6 weeks of pilot deployment, the SmartCDS system suppressed an average of 43.67% (15,425/35,315) potential shingles alerts (appointments) and maintained stable counts of weekly shingles vaccination orders (326.3 with system active vs 331.3 in the control group; P=.38) and weekly user-alert interactions (1118.3 with system active vs 1166.3 in the control group; P=.20). CONCLUSIONS:All key statistics remained stable while the system was turned on. Although the results are promising, the characteristics of the system can be subject to future data shifts, which require automated logging and monitoring. We demonstrated that an automated, ML-based method and data architecture to suppress alerts are feasible without detriment to overall order rates. This work is the first alert suppression ML-based model deployed in practice and serves as foundational work in encounter-level customization of alert display to maximize effectiveness.
PMID: 32347813
ISSN: 1438-8871
CID: 4412352