Faculty Bibliography

BACKGROUND:We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS:IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021. RESULTS:Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030). CONCLUSIONS:The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.

OBJECTIVES/OBJECTIVE:National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing. METHODS:This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered. RESULTS:Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs). CONCLUSIONS:This low-effort, electronic health record-based intervention can effectively reduce unnecessary laboratory testing.

OBJECTIVE/UNASSIGNED:, the gene encoding the anti-inflammatory IL-1 receptor antagonist (IL-1Ra), on the cytokine release syndrome and mortality. METHODS/UNASSIGNED:gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. RESULTS/UNASSIGNED:rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052), with the most pronounced effect observed between the ages of 55-74 [5.5% vs. 18.4%, p<0.001]. CONCLUSION/UNASSIGNED:modulates the COVID-19 cytokine release syndrome via endogenous " anti-inflammatory" mechanisms. SIGNIFICANCE STATEMENT/UNASSIGNED:merits further evaluation in severe SARS-CoV-2 infection.

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.

OBJECTIVE:The patient-physician relationship impacts patients' experiences and health outcomes. Physician attire is a form of nonverbal communication that influences this relationship. Prior studies examining attire preferences suffered from heterogeneous measurement and limited context. We thus performed a multicentre, cross-sectional study using a standardised survey instrument to compare patient preferences for physician dress in international settings. SETTING:20 hospitals and healthcare practices in Italy, Japan, Switzerland and the USA. PARTICIPANTS:Convenience sample of 9171 adult patients receiving care in academic hospitals, general medicine clinics, specialty clinics and ophthalmology practices. PRIMARY AND SECONDARY OUTCOME MEASURES:The survey was randomised and included photographs of a male or female physician dressed in assorted forms of attire. The primary outcome measure was attire preference, comprised of composite ratings across five domains: how knowledgeable, trustworthy, caring and approachable the physician appeared, and how comfortable the respondent felt. Secondary outcome measures included variation in preferences by country, physician type and respondent characteristics. RESULTS:The highest rated forms of attire differed by country, although each most preferred attire with white coat. Low ratings were conferred on attire extremes (casual and business suit). Preferences were more uniform for certain physician types. For example, among all respondents, scrubs garnered the highest rating for emergency department physicians (44.2%) and surgeons (42.4%). However, attire preferences diverged for primary care and hospital physicians. All types of formal attire were more strongly preferred in the USA than elsewhere. Respondent age influenced preferences in Japan and the USA only. CONCLUSIONS:Patients across a myriad of geographies, settings and demographics harbour specific preferences for physician attire. Some preferences are nearly universal, whereas others vary substantially. As a one-size-fits-all dress policy is unlikely to reflect patient desires and expectations, a tailored approach should be sought that attempts to match attire to clinical context.

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.

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/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.

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