Faculty Bibliography

Background/Purpose: 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 alleles contribute to the genetic high IFN trait. In this study, we examine whether these common gain-of-function alleles in the type I IFN pathway are associated with protection from mortality in acute COVID-19.
Method(s): We studied IFN pathway SLE risk genes in patients with acute COVID-19 admitted to NYU Langone hospitals (751 European-American and 398 African-American ancestry). The samples were genotyped using low depth sequencing and imputation, and we analyzed data from the following SNPs: IRF5 (rs2004640, rs3807306, rs10488631, rs2280714), IRF7/PHRF (rs1131665, rs4963128), IRF8 (rs17445836, rs12444486), and PRKG1 (rs7897633). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome.
Result(s): We observed specific IRF5 haplotypes that are protective against SLE risk were associated with increased risk of mortality in acute COVID-19 patients in European-American ancestry (OR=3.74, p=0.015). Alleles of PRKG1 were also associated with mortality from COVID-19 in the European-American ancestry cohort (OR=1.80, p=0.0057), and this risk factor was particularly strong in younger patients (OR=29.2, p=0.01 in ages 45-54). IRF8 genotype at rs1244486 was associated with protection from mortality in COVID-19 in African-American subjects aged 65 and older (OR=0.34, p=0.04).
Conclusion(s): We find that a number of type I IFN pathway genes associated with risk of SLE also modulate risk of death during acute COVID-19. Similar to their associations with SLE, these alleles are variably associated with COVID-19 mortality across ancestral backgrounds, suggesting ancestral differences in the genetic regulation of the IFN pathway. These data confirm the critical role of the IFN pathway in our defense against viral infections, and support the idea that some common SLE risk alleles exert protective effects in anti-viral immunity

Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.

Early reports showed high mortality from coronavirus disease 2019 (COVID-19). Mortality rates have recently been lower; however, patients are also now younger, with fewer comorbidities. We explored 28-day mortality for patients hospitalized for COVID-19 in England over a 5-month period, adjusting for a range of potentially mitigating variables, including sociodemographics and comorbidities. Among 102,610 hospitalizations, crude mortality decreased from 33.4% (95% CI, 32.9-34.0) in March 2020 to 15.5% (95% CI, 14.1-17.0) in July. Adjusted mortality decreased from 33.4% (95% CI, 32.8-34.1) in March to 17.4% (95% CI, 11.3-26.9) in July. The relative risk of mortality decreased from a reference of 1 in March to 0.52 (95% CI, 0.34-0.80) in July. This demonstrates that the reduction in mortality is not solely due to changes in the demographics of those with COVID-19.

Introduction/UNASSIGNED:Reports from the United States suggest that acute kidney injury (AKI) frequently complicates COVID-19, but understanding of AKI risks and outcomes is incomplete. Additionally, whether kidney outcomes have evolved during the course of the pandemic is unknown. Methods/UNASSIGNED:We used electronic records to identify COVID-19 patients with and without AKI admitted to 3 New York Hospitals between March 2 and August 25, 2020. Outcomes included AKI overall and according to admission week, AKI stage, the requirement for new renal replacement therapy (RRT), mortality and recovery of kidney function. Logistic regression was utilized to assess associations of patient characteristics and outcomes. Results/UNASSIGNED:Out of 4732 admissions 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had Stage 1, 132 (9.5%) Stage 2, 537 (38.7%) stage 3, and 237 (17.1%) required RRT initiation. In March 536/1648 (32.5%) of patients developed AKI compared with 15/87 (17.2%) in August (P<0.001 for monthly trend) whereas RRT initiation was required in 6.9% and 0% of admission, in March and August respectively. Mortality was higher with than without AKI (51.6% vs 8.6%) and was 71.9% in individuals requiring RRT. However, most patients with AKI who survived hospitalization (77%) recovered to within 0.3 mg/dL of baseline creatinine. Among those surviving to discharge, 62% discontinued RRT. Conclusions/UNASSIGNED:AKI impacts a high proportion of admitted COVID-19 patients and is associated with high mortality, particularly when RRT is required. AKI incidence appears to be decreasing over time and kidney function frequently recovers in those who survive.

Early reports showed high mortality from coronavirus disease 2019 (COVID-19). Mortality rates have recently been lower, raising hope that treatments have improved. However, patients are also now younger, with fewer comorbidities. We explored whether hospital mortality was associated with changing demographics at a 3-hospital academic health system in New York. We examined in-hospital mortality or discharge to hospice from March through August 2020, adjusted for demographic and clinical factors, including comorbidities, admission vital signs, and laboratory results. Among 5,121 hospitalizations, adjusted mortality dropped from 25.6% (95% CI, 23.2-28.1) in March to 7.6% (95% CI, 2.5-17.8) in August. The standardized mortality ratio dropped from 1.26 (95% CI, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August, at which time the average probability of death (average marginal effect) was 18.2 percentage points lower than in March. Data from one health system suggest that mortality from COVID-19 is decreasing even after accounting for patient characteristics.

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.

Introduction. COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.Aim. To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone.Methodology. This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19.Results. Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (n=411) and patients taking hydroxychloroquine and azithromycin alone (n=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12-2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449, 95 % CI 0.271-0.744).Conclusion. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.

BACKGROUND:Previous studies have shown that patients have specific expectations regarding physician dress. Japan has a cultural background that is in many ways distinct from western countries. Thus, physician attire may have a different impact in Japan. METHODS:We conducted a multicenter, cross-sectional study to examine patients' preferences for and perceptions of physician attire in Japan. The questionnaire was developed using photographs of either a male or female physician dressed in seven different forms of attire, and it was randomly distributed to inpatients and outpatients. Respondents were asked to rate the provider pictured; they were also asked to provide preferences for different forms of attire in varied clinical settings. Preference was evaluated for five domains (knowledgeable, trustworthy, caring, approachable, and comfortable). We also assessed variation in preferences for attire by respondent characteristics. RESULTS:A total of 1,233 (61%) patients indicated that physician dress was important, and 950 (47%) patients agreed that it influenced their satisfaction with care. Compared with all forms, casual attire with a white coat was the most preferred dress. Older patients more often preferred formal attire with a white coat in primary care and hospital settings. In addition, physician attire had a greater impact on older respondents' satisfaction and experience. CONCLUSION/CONCLUSIONS:The majority of Japanese patients indicated that physician attire is important and influenced their satisfaction with care. Geography, settings of care, and patient age appear to play a role in patient preferences.