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Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin

Nolan, Margaret B; Piasecki, Thomas M; Smith, Stevens S; Baker, Timothy B; Fiore, Michael C; Adsit, Robert T; Bolt, Daniel M; Conner, Karen L; Bernstein, Steven L; Eng, Oliver D; Lazuk, David; Gonzalez, Alec; Hayes-Birchler, Todd; Jorenby, Douglas E; D'Angelo, Heather; Kirsch, Julie A; Williams, Brian S; Kent, Sean; Kim, Hanna; Lubanski, Stanley A; Yu, Menggang; Suk, Youmi; Cai, Yuxin; Kashyap, Nitu; Mathew, Jomol; McMahan, Gabriel; Rolland, Betsy; Tindle, Hilary A; Warren, Graham W; Abu-El-Rub, Noor; An, Lawrence C; Boyd, Andrew D; Brunzell, Darlene H; Carrillo, Victor A; Chen, Li-Shiun; Davis, James M; Deshmukh, Vikrant G; Dilip, Deepika; Goldstein, Adam; Ha, Patrick K; Iturrate, Eduardo; Jose, Thulasee; Khanna, Niharika; King, Andrea; Klass, Elizabeth; Lui, Michelle; Mermelstein, Robin J; Poon, Chester; Tong, Elisa; Wilson, Karen M; Theobald, Wendy E; Slutske, Wendy S
BACKGROUND:There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS:Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS:6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aORs) for mortality were 1.58 (95% CI: 1.46, 1.70) and 1.04 (95% CI: 0.96, 1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and amongst those with current cancer (aOR = 0.69, 95% CI = 0.53 to 0.90). CONCLUSIONS:Current cancer, especially amongst younger patients, posed a substantially increased risk for death and ICU admission among COVID-19 patients; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT/CONCLUSIONS:This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic.
PMID: 35965473
ISSN: 1538-7755
CID: 5299702

The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study

Nagler, Arielle R; Horwitz, Leora I; Jones, Simon; Petrilli, Christopher M; Iturrate, Eduardo; Lighter, Jennifer L; Phillips, Michael; Bosworth, Brian P; Polsky, Bruce; Volpicelli, Frank M; Dapkins, Isaac; Viswanathan, Anand; François, Fritz; Kalkut, Gary
DISCLAIMER/CONCLUSIONS:In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE/OBJECTIVE:Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS:A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS:A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.
PMID: 36242772
ISSN: 1535-2900
CID: 5361302

Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness

Mukhopadhyay, Amrita; Talmor, Nina; Xia, Yuhe; Berger, Jeffrey S; Iturrate, Eduardo; Adhikari, Samrachana; Pulgarin, Claudia; Quinones-Camacho, Adriana; Yuriditsky, Eugene; Horowitz, James; Jung, Albert S; Massera, Daniele; Keller, Norma M; Fishman, Glenn I; Horwitz, Leora; Troxel, Andrea B; Hochman, Judith S; Reynolds, Harmony R
BACKGROUND:Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE:We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS:We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS:Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION/CONCLUSIONS:Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.
PMID: 36334466
ISSN: 1527-3288
CID: 5358922

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study

Piasecki, Thomas M; Smith, Stevens S; Baker, Timothy B; Slutske, Wendy S; Adsit, Robert T; Bolt, Daniel M; Conner, Karen L; Bernstein, Steven L; Eng, Oliver D; Lazuk, David; Gonzalez, Alec; Jorenby, Douglas E; D'Angelo, Heather; Kirsch, Julie A; Williams, Brian S; Nolan, Margaret B; Hayes-Birchler, Todd; Kent, Sean; Kim, Hanna; Lubanski, Stan; Yu, Menggang; Suk, Youmi; Cai, Yuxin; Kashyap, Nitu; Mathew, Jomol P; McMahan, Gabriel; Rolland, Betsy; Tindle, Hilary A; Warren, Graham W; An, Lawrence C; Boyd, Andrew D; Brunzell, Darlene H; Carrillo, Victor; Chen, Li-Shiun; Davis, James M; Deshmukh, Vikrant G; Dilip, Deepika; Ellerbeck, Edward F; Goldstein, Adam O; Iturrate, Eduardo; Jose, Thulasee; Khanna, Niharika; King, Andrea; Klass, Elizabeth; Mermelstein, Robin J; Tong, Elisa; Tsoh, Janice Y; Wilson, Karen M; Theobald, Wendy E; Fiore, Michael C
INTRODUCTION/BACKGROUND:Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS:Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS:Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS:Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS/CONCLUSIONS:Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.
PMID: 36069915
ISSN: 1469-994x
CID: 5337002

The Impact of Telemedicine on Physicians' After-hours Electronic Health Record "Work Outside Work" During the COVID-19 Pandemic: Retrospective Cohort Study

Lawrence, Katharine; Nov, Oded; Mann, Devin; Mandal, Soumik; Iturrate, Eduardo; Wiesenfeld, Batia
BACKGROUND:Telemedicine as a mode of health care work has grown dramatically during the COVID-19 pandemic; the impact of this transition on clinicians' after-hours electronic health record (EHR)-based clinical and administrative work is unclear. OBJECTIVE:This study assesses the impact of the transition to telemedicine during the COVID-19 pandemic on physicians' EHR-based after-hours workload (ie, "work outside work") at a large academic medical center in New York City. METHODS:We conducted an EHR-based retrospective cohort study of ambulatory care physicians providing telemedicine services before the pandemic, during the acute pandemic, and after the acute pandemic, relating EHR-based after-hours work to telemedicine intensity (ie, percentage of care provided via telemedicine) and clinical load (ie, patient load per provider). RESULTS:A total of 2129 physicians were included in this study. During the acute pandemic, the volume of care provided via telemedicine significantly increased for all physicians, whereas patient volume decreased. When normalized by clinical load (ie, average appointments per day by average clinical days per week), telemedicine intensity was positively associated with work outside work across time periods. This association was strongest after the acute pandemic. CONCLUSIONS:Taking physicians' clinical load into account, physicians who devoted a higher proportion of their clinical time to telemedicine throughout various stages of the pandemic engaged in higher levels of EHR-based after-hours work compared to those who used telemedicine less intensively. This suggests that telemedicine, as currently delivered, may be less efficient than in-person-based care and may increase the after-hours work burden of physicians.
PMID: 35749661
ISSN: 2291-9694
CID: 5282312

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

Duerr, Ralf; Dimartino, Dacia; Marier, Christian; Zappile, Paul; Levine, Samuel; Francois, Fritz; Iturrate, Eduardo; Wang, Guiqing; Dittmann, Meike; Lighter, Jennifer; Elbel, Brian; Troxel, Andrea B; Goldfeld, Keith S; Heguy, Adriana
BACKGROUND:In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. METHODS:We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. FINDINGS/RESULTS: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 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. INTERPRETATION/CONCLUSIONS:We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. FUNDING/BACKGROUND:The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.
PMID: 35906172
ISSN: 2352-3964
CID: 5277042

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

Pathogen Species Is Associated With Mortality in Nosocomial Bloodstream Infection in Patients With COVID-19

Gago, Juan; Filardo, Thomas D; Conderino, Sarah; Magaziner, Samuel J; Dubrovskaya, Yanina; Inglima, Kenneth; Iturrate, Eduardo; Pironti, Alejandro; Schluter, Jonas; Cadwell, Ken; Hochman, Sarah; Li, Huilin; Torres, Victor J; Thorpe, Lorna E; Shopsin, Bo
Background/UNASSIGNED:The epidemiology of nosocomial bloodstream infections (NBSIs) in patients with coronavirus disease 2019 (COVID-19) is poorly understood, due in part to substantial disease heterogeneity resulting from multiple potential pathogens. Methods/UNASSIGNED:We identified risk factors for NBSIs and examined the association between NBSIs and mortality in a retrospective cohort of patients hospitalized with COVID-19 in 2 New York City hospitals during the height of the pandemic. We adjusted for the potential effects of factors likely to confound that association, including age, race, illness severity upon admission, and underlying health status. Results/UNASSIGNED:infections did not have an identifiable source and were not associated with common risk factors for infection by these organisms. Conclusions/UNASSIGNED:Pathogen species and mortality exhibited temporal differences. Early recognition of risk factors among COVID-19 patients could potentially decrease NBSI-associated mortality through early COVID-19 and antimicrobial treatment.
PMID: 35607701
ISSN: 2328-8957
CID: 5283852

The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome

Katz, Alyson; Altshuler, Diana; Papadopoulos, John; Amoroso, Nancy; Goldenberg, Ronald; Tarras, Elizabeth; Krolikowski, Kelsey; Hagedorn, Jacklyn; Fridman, David; Chen, Xian Jie Cindy; Iturrate, Eduardo; Brosnahan, Shari B
BACKGROUND/UNASSIGNED:Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE/UNASSIGNED:The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS/UNASSIGNED:This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS/UNASSIGNED:= 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS/UNASSIGNED:In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.
PMID: 35590468
ISSN: 1542-6270
CID: 5247692

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