IMPORTANCE The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. OBJECTIVES To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. EXPOSURES Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. MAIN OUTCOMES AND MEASURES The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. RESULTS A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (Ն80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (Ն40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (PaO 2 :FIO 2 <100 vs Ն300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs Ն100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. CONCLUSIONS AND RELEVANCE This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

IMPORTANCE Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. OBJECTIVE To test whether tocilizumab decreases mortality in this population. DESIGN, SETTING, AND PARTICIPANTS The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. EXPOSURES Treatment with tocilizumab in the first 2 days of ICU admission. MAIN OUTCOMES AND MEASURES Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. RESULTS Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). CONCLUSIONS AND RELEVANCE Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

BackgroundAKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT).MethodsWe conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients.ResultsA total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1–123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission.ConclusionsAKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

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Objective Hyperchloremia is frequently observed in critically ill patients in the intensive care unit (ICU). Our study aimed to examine the association of serum chloride (Cl) levels with hospital mortality in septic ICU patients. Design Retrospective cohort study. Setting Urban academic medical center ICU. Patients ICU adult patients with severe sepsis or septic shock who had Cl measured on ICU admission were included. Those with baseline estimated glomerular filtration rate < 15 ml/min/1.73 m2 or chronic dialysis were excluded. Intervention: None. Measurements and Main Results Of 1940 patients included in the study, 615 (31.7%) had hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission. All-cause hospital mortality was the dependent variable. Cl on ICU admission (Cl0), Cl at 72 h (Cl72), and delta Cl (ΔCl = Cl72 – Cl0) were the independent variables. Those with Cl0 ≥ 110 mEq/L were older and had higher cumulative fluid balance, base deficit, and sequential organ failure assessment scores. Multivariate analysis showed that higher Cl72 but not Cl0 was independently associated with hospital mortality in the subgroup of patients with hyperchloremia on ICU admission [adjusted odds ratio (OR) for Cl72 per 5 mEq/L increase = 1.27, 95% CI (1.02–1.59), P = 0.03]. For those who were hyperchloremic on ICU admission, every within-subject 5 mEq/L increment in Cl72 was independently associated with hospital mortality [adjusted OR for ΔCl 5 mEq/L = 1.37, 95% CI [1.11–1.69], P = 0.003]. Conclusions In critically ill septic patients manifesting hyperchloremia (Cl ≥110 mEq/L) on ICU admission, higher Cl levels and within-subject worsening hyperchloremia at 72 h of ICU stay were associated with all-cause hospital mortality. These associations were independent of base deficit, cumulative fluid balance, acute kidney injury, and other critical illness parameters.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID‐19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory‐confirmed COVID‐19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non‐SOT patients. We used a binomial generalized linear model (log‐binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non‐SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70‐1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non‐SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97‐1.85]). Death and organ support requirement were similar between SOT and non‐SOT critically ill patients with COVID‐19.

Objective Incident acute kidney injury (AKI) and prevalent chronic kidney disease (CKD) are commonly encountered in septic patients. We examined the differential effect of AKI and CKD on the association between cumulative fluid balance (CFB) and hospital mortality in critically ill septic patients. Design Retrospective cohort study. Setting Urban academic medical center ICU. Patients ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 h of ICU admission. Patients with estimated glomerular filtration rate <15 mL/min/1.73m2 or receiving chronic dialysis were excluded. Interventions None. Measurements and Main Results 2632 patients, 1211 with CKD, were followed until hospital death or discharge. AKI occurred in 1525 (57.9%), of whom 679 (44.5%) had CKD. Hospital mortality occurred in 603 (22.9%) patients. Every 1 L increase in CFB at 72 h of ICU admission was independently associated with hospital mortality in all patients, adjusted odds ratio (aOR) 1.06, 95% CI (1.04–1.08), p <0.001, and in each AKI/CKD subgroup: aOR 1.06 (1.03–1.09) for AKI+/CKD+; 1.09 (1.05–1.13) for AKI−/CKD+; 1.05 (1.03–1.08) for AKI+/CKD−; and 1.07 (1.02–1.11) for AKI−/CKD−. There was a significant interaction between AKI and CKD on CFB, p =0.005, such that different CFB cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for AKI+/CKD+; 3.8 L for AKI−/CKD+; 4.3 L for AKI+/CKD−; and 1.5 L for AKI−/CKD−. The addition of CFB to the admission SOFA score had increased prognostic utility for hospital mortality when compared to SOFA alone, particularly in patients with AKI. Conclusions Higher CFB at 72 h of ICU admission was independently associated with hospital mortality regardless of AKI or CKD presence. We characterized CFB cut-offs associated with hospital mortality based on AKI/CKD status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

The extracellular domain of transmembrane alpha-Klotho (αKlotho, hereinafter simply called Klotho) is cleaved by secretases and released into the circulation as soluble Klotho. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism. Prevention of Klotho decline, re-activation of endogenous Klotho production or supplementation of exogenous Klotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiomyopathy, and alleviation of vascular calcification in CKD. Therefore Klotho is not only a diagnostic and/or prognostic marker for CKD, but the treatment of Klotho deficiency may be a promising strategy to prevent, retard, and decrease the burden of comorbidity in CKD.