Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19.

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.

Initiative to reduce unnecessary routine daily testing of complete blood counts across 11 safety net hospitals.

OBJECTIVES: 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.

Interleukin-1 receptor antagonist gene ( IL1RN ) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2.

Objective: To explore the regulation of the inflammatory response in acute SARS-CoV-2 infection, we examined effects of single nucleotide variants (SNVs) of IL1RN , the gene encoding the anti-inflammatory IL-1 receptor antagonist (IL-1Ra), on the cytokine release syndrome and mortality. Methods: We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021 at NYU Langone's Tisch Hospital. CTA and TTG haplotypes formed from three SNVs (rs419598, rs315952, rs9005) and the individual SNVs of the IL1RN gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. Results: Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA-1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN 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: The IL1RN haplotype CTA, and sequence variant of rs419598 are associated with attenuation of the cytokine release syndrome and decreased mortality in males with acute SARS-CoV2 infection. The data suggest that IL1RN modulates the COVID-19 cytokine release syndrome via endogenous " anti-inflammatory" mechanisms. Significance statement: We provide evidence that variants of IL1RN modulate the severity of SARS-CoV-2 infection. The IL1RN CTA haplotype and rs419598 CC single nucleotide variant are associated with decreased plasma levels of inflammatory markers, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-2 (IL-2), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin, in association with higher levels of IL-1Ra and IL-10, anti-inflammatory proteins. Both haplotype CTA and rs419598 CC genotype are associated with a significant reduction in the mortality of men. These data provide genetic evidence that inflammasome activation and the IL-1 pathway plays an important role in the mortality and morbidity associated with severe SARS-CoV-2 infection, and that genetic regulation of inflammatory pathways by variants of IL1RN merits further evaluation in severe SARS-CoV-2 infection.

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

PURPOSE: 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.

International patient preferences for physician attire: results from cross-sectional studies in four countries across three continents.

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.

Interferon pathway lupus risk alleles modulate risk of death from acute 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 antiviral immunity.

Interferon pathway lupus risk alleles modulate risk of death from acute 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: 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.

Prior bariatric surgery in COVID-19-positive patients may be protective.

BACKGROUND: Patients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data have shown that age, sex, and obesity are strongly correlated with poor outcomes in COVID-19-positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese. OBJECTIVES: Examine if prior bariatric surgery correlates with increased risk of hospitalization and outcome severity after COVID-19 infection. SETTING: University hospital METHODS: A cross-sectional retrospective analysis of a COVID-19 database from a single, New York City-based, academic institution was conducted. A cohort of COVID-19-positive patients with a history of bariatric surgery (n = 124) were matched in a 1:4 ratio to a control cohort of COVID-19-positive patients who were eligible for bariatric surgery (BMI ≥40 kg/m2 or BMI >35 kg/m2 with a co-morbidity at the time of COVID-19 diagnosis) (n = 496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using χ2 test or Fisher's exact test. Additionally, overall length of stay and duration of time in intensive care unit (ICU) were compared using Wilcoxon rank sum test. Conditional logistic regression analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR). RESULTS: A total of 620 COVID-19-positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y gastric bypass (RYGB, n = 45), 36% laparoscopic adjustable gastric banding (LAGB, n = 44), and 28% laparoscopic sleeve gastrectomy (LSG, n = 35). The body mass index (BMI) for the bariatric group was 36.1 kg/m2 (SD = 8.3), which was significantly lower than the control group, 41.4 kg/m2 (SD = 6.5, P < .0001). There was also less burden of diabetes in the bariatric group (32%) compared with the control group (48%) (P = .0019). Patients with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR = .39, P = .0001), less likely to require a ventilator during the admission (UOR=.42, P = .028), had a shorter length of stay in both the ICU (P = .033) and overall (UOR = .44, P = .0002), and were less likely to be deceased at discharge compared with the control group (OR = .42, P = .028). CONCLUSION: A history of bariatric surgery significantly decreases the risk of emergency room admission, mechanical ventilation, prolonged ICU stay, and death in patients with COVID-19. Even when adjusted for BMI and the co-morbidities associated with obesity, patients with a history of bariatric surgery still have a significant decrease in the risk of emergency room admission.

Trends in Risk-Adjusted 28-Day Mortality Rates for Patients Hospitalized with COVID-19 in England.

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.

Decreasing Incidence of Acute Kidney Injury in Patients with COVID-19 Critical Illness in New York City.

INTRODUCTION: Reports from the United States suggest that acute kidney injury (AKI) frequently complicates coronavirus disease 2019 (COVID-19), but understanding of AKI risks and outcomes is incomplete. In addition, whether kidney outcomes have evolved during the course of the pandemic is unknown. METHODS: We used electronic medical records to identify patients with COVID-19 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 used to assess associations of patient characteristics and outcomes. RESULTS: Of 4732 admissions, 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had stage 1 disease, 132 (9.5%) had stage 2 disease, 537 (38.7%) had stage 3 disease, and 237 (17.1%) required RRT initiation. In March, 536 of 1648 (32.5%) patients developed AKI compared with 15 of 87 (17.2%) in August (P < 0.001 for monthly trend), whereas RRT initiation was required in 6.9% and 0% of admissions 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: AKI impacts a high proportion of admitted patients with COVID-19 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.

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19.

Background: 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: 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: 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: 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.

Trends in COVID-19 Risk-Adjusted Mortality Rates.

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.

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

Importance: 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: 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: 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: 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: 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: 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: 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.

Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients.

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.

Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19.

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study.

OBJECTIVE: To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. DESIGN: Prospective cohort study. SETTING: Single academic medical center in New York City and Long Island. PARTICIPANTS: 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. MAIN OUTCOME MEASURES: Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. RESULTS: Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of <88% (3.7, 2.8 to 4.8), troponin level >1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. CONCLUSIONS: Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.

Patient Preferences for Physician Attire: A Multicenter Study in Japan.

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: 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.

Patient Preferences for Physician Attire in Ophthalmology Practices.

IMPORTANCE: Interest is growing in targeting physician attire to improve the patient experience. Few studies in ophthalmology have examined patient preferences for physician attire. OBJECTIVE: To understand patient preferences for physician attire in ophthalmology practices in the United States. DESIGN: Survey-based, cohort study. SETTING: Two private and two academic ophthalmology practices. PARTICIPANTS: A convenience sample of patients receiving ophthalmic care between June 1, 2015 and October 31, 2016. METHODS: A questionnaire containing 22 questions and photographs of a male and female physician in seven forms of attire were presented to patients; 14 unique questionnaires were randomly distributed. Patient preference for physician attire was the primary outcome determined by summing ratings of how knowledgeable, trustworthy, caring, approachable, and comfortable the pictured physician made the respondent feel. One-way ANOVA assessed differences in mean composite scores. Comparisons between respondent demographics, practice type, and attire preferences were assessed by chi-square tests. Patient satisfaction was assessed by agreement with questions about importance of physician attire and whether this influences happiness with care. RESULTS: In total, 1,297 of 1,826 (71.0%) questionnaires were completed. Physician attire was rated as "important" by 62.9% of participants. A total of 43.6% of participants indicated that physician attire influenced how happy they were with their care. Overall, formal attire with white coat was preferred to casual, formal, and business attire (all comparisons, p < 0.05). No differences in composite scores between formal attire with white coat, scrubs alone, scrubs with white coat, or casual attire with white coat were observed. However, compared with formal attire with white coat, physicians wearing scrubs without white coat appeared less knowledgeable (mean [standard deviation]: 8.2 [1.8] vs. 7.4 [2.1]; p < 0.05) and trustworthy (8.3 [1.8] vs. 7.6 [2.1]; p < 0.05). Additionally, casual attire with white coat was rated as less knowledgeable compared with formal attire with white coat (7.4 [2.0] vs. 8.2 [1.8]; p < 0.05). Preferences for attire varied by clinical setting: patients preferred surgeons (45.2%) and physicians in emergency rooms (41.7%) in scrubs rather than formal attire with white coat. CONCLUSIONS: Physician attire is important to patients receiving ophthalmic care. Policies aimed at physician attire in ophthalmology practices should be considered.