Target Trial Emulation: A Framework for Causal Inference From Observational Data.

This Guide to Statistics and Methods describes the use of target trial emulation to design an observational study so it preserves the advantages of a randomized clinical trial, points out the limitations of the method, and provides an example of its use.

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Therapeutic advances in COVID-19.

Over 2 years have passed since the start of the COVID-19 pandemic, which has claimed millions of lives. Unlike the early days of the pandemic, when management decisions were based on extrapolations from in vitro data, case reports and case series, clinicians are now equipped with an armamentarium of therapies based on high-quality evidence. These treatments are spread across seven main therapeutic categories: anti-inflammatory agents, antivirals, antithrombotics, therapies for acute hypoxaemic respiratory failure, anti-SARS-CoV-2 (neutralizing) antibody therapies, modulators of the renin-angiotensin-aldosterone system and vitamins. For each of these treatments, the patient population characteristics and clinical settings in which they were studied are important considerations. Although few direct comparisons have been performed, the evidence base and magnitude of benefit for anti-inflammatory and antiviral agents clearly outweigh those of other therapeutic approaches such as vitamins. The emergence of novel variants has further complicated the interpretation of much of the available evidence, particularly for antibody therapies. Importantly, patients with acute and chronic kidney disease were under-represented in many of the COVID-19 clinical trials, and outcomes in this population might differ from those reported in the general population. Here, we examine the clinical evidence for these therapies through a kidney medicine lens.

Relationship Between Preexisting Cardiovascular Disease and Death and Cardiovascular Outcomes in Critically Ill Patients With COVID-19.

BACKGROUND: Preexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19. METHODS: This study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days. RESULTS: Among 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD. CONCLUSIONS: CVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD. REGISTRATION: NCT04343898; https://clinicaltrials.gov/ct2/show/NCT04343898.

Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19.

Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.

Hispanic ethnicity and mortality among critically ill patients with COVID-19.

BACKGROUND: Hispanic persons living in the United States (U.S.) are at higher risk of infection and death from coronavirus disease 2019 (COVID-19) compared with non-Hispanic persons. Whether this disparity exists among critically ill patients with COVID-19 is unknown. OBJECTIVE: To evaluate ethnic disparities in mortality among critically ill adults with COVID-19 enrolled in the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID). METHODS: Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICU) at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day mortality across racial/ethnic groups. RESULTS: A total of 2153 patients were included (994 [46.2%] Hispanic and 1159 [53.8%] non-Hispanic White). The median (IQR) age was 62 (51-71) years (non-Hispanic White, 66 [57-74] years; Hispanic, 56 [46-67] years), and 1462 (67.9%) were men. Compared with non-Hispanic White patients, Hispanic patients were younger; were less likely to have hypertension, chronic obstructive pulmonary disease, coronary artery disease, or heart failure; and had longer duration of symptoms prior to ICU admission. During median (IQR) follow-up of 14 (7-24) days, 785 patients (36.5%) died. In analyses adjusted for age, sex, clinical characteristics, and hospital size, Hispanic patients had higher odds of death compared with non-Hispanic White patients (OR, 1.44; 95% CI, 1.12-1.84). CONCLUSIONS: Among critically ill adults with COVID-19, Hispanic patients were more likely to die than non-Hispanic White patients, even though they were younger and had lower comorbidity burden. This finding highlights the need to provide earlier access to care to Hispanic individuals with COVID-19, especially given our finding of longer duration of symptoms prior to ICU admission among Hispanic patients. In addition, there is a critical need to address ongoing disparities in post hospital discharge care for patients with COVID-19.

Sex-related differences in mortality, acute kidney injury, and respiratory failure among critically ill patients with COVID-19.

ABSTRACT: Although the number of deaths due to coronavirus disease 2019 (COVID-19) is higher in men than women, prior studies have provided limited sex-stratified clinical data.We evaluated sex-related differences in clinical outcomes among critically ill adults with COVID-19.Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day in-hospital mortality, severe acute kidney injury (AKI requiring kidney replacement therapy), and respiratory failure occurring within 14 days of intensive care unit admission.A total of 4407 patients were included (median age, 62 years; 2793 [63.4%] men; 1159 [26.3%] non-Hispanic White; 1220 [27.7%] non-Hispanic Black; 994 [22.6%] Hispanic). Compared with women, men were younger (median age, 61 vs 64 years, less likely to be non-Hispanic Black (684 [24.5%] vs 536 [33.2%]), and more likely to smoke (877 [31.4%] vs 422 [26.2%]). During median follow-up of 14 days, 1072 men (38.4%) and 553 women (34.3%) died. Severe AKI occurred in 590 men (21.8%), and 239 women (15.5%), while respiratory failure occurred in 2255 men (80.7%) and 1234 women (76.5%). After adjusting for age, race/ethnicity and clinical variables, compared with women, men had a higher risk of death (OR, 1.50, 95% CI, 1.26-1.77), severe AKI (OR, 1.92; 95% CI 1.57-2.36), and respiratory failure (OR, 1.42; 95% CI, 1.11-1.80).In this multicenter cohort of critically ill adults with COVID-19, men were more likely to have adverse outcomes compared with women.

Association of Surge Conditions with Mortality Among Critically Ill Patients with COVID-19.

OBJECTIVE: To determine whether surge conditions were associated with increased mortality. DESIGN: Multicenter cohort study. SETTING: U.S. ICUs participating in STOP-COVID. PATIENTS: Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 - May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals).Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p < .001). CONCLUSIONS: Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study.

RATIONALE & OBJECTIVE: Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with coronavirus disease 2019 (COVID-19). We examined the clinical factors that determine kidney recovery in this population. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 4,221 adults not receiving KRT who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the "ICU cohort"). Among these, 876 developed AKI-KRT after admission to the ICU (the "AKI-KRT subcohort"). EXPOSURE: The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of KRT initiation. OUTCOME: The outcome for the ICU cohort was estimated glomerular filtration rate (eGFR) at hospital discharge. A 3-level outcome (death, kidney nonrecovery, and kidney recovery at discharge) was analyzed for the AKI-KRT subcohort. ANALYTICAL APPROACH: The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. RESULTS: Among a total of 4,221 patients in the ICU cohort, 2,361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower baseline eGFR, with ORs of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for baseline eGFR 31-60, 16-30, ≤15 mL/min/1.73 m2, respectively, compared with eGFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (ORs of 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and <50 mL/d of urine, respectively, compared to ≥500 mL/d of urine). LIMITATIONS: Later recovery events may not have been captured due to lack of postdischarge follow-up. CONCLUSIONS: Lower baseline eGFR and reduced urine output at the time of KRT initiation are each strongly and independently associated with kidney nonrecovery among critically ill patients with COVID-19.

Protocol to assess performance of crisis standards of care guidelines for clinical triage.

During the COVID-19 pandemic, US states developed Crisis Standards of Care (CSC) algorithms to triage allocation of scarce resources to maximize population-wide benefit. While CSC algorithms were developed by ethical debate, this protocol guides their quantitative assessment. For CSC algorithms, this protocol addresses (1) adapting algorithms for empirical study, (2) quantifying predictive accuracy, and (3) simulating clinical decision-making. This protocol provides a framework for healthcare systems and governments to test the performance of CSC algorithms to ensure they meet their stated ethical goals. For complete details on the use and execution of this protocol, please refer to Jezmir et al. (2021).

Severe autoimmune hemolytic anemia following receipt of SARS-CoV-2 mRNA vaccine.

BACKGROUND: Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia. CASE PRESENTATION: Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin. CONCLUSION: As efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies.

Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN: This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING: Sixty-eight U.S. ICUs. PATIENTS: Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS: eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure.

OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

A Systematic Review of the Incidence and Outcomes of In-Hospital Cardiac Arrests in Patients With Coronavirus Disease 2019.

OBJECTIVES: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age. DATA SOURCES: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369. STUDY SELECTION: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer. DATA SYNTHESIS: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0-11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019). CONCLUSIONS: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed.

Obesity, inflammatory and thrombotic markers, and major clinical outcomes in critically ill patients with COVID-19 in the US.

OBJECTIVE: This study aimed to determine whether obesity is independently associated with major adverse clinical outcomes and inflammatory and thrombotic markers in critically ill patients with COVID-19. METHODS: The primary outcome was in-hospital mortality in adults with COVID-19 admitted to intensive care units across the US. Secondary outcomes were acute respiratory distress syndrome (ARDS), acute kidney injury requiring renal replacement therapy (AKI-RRT), thrombotic events, and seven blood markers of inflammation and thrombosis. Unadjusted and multivariable-adjusted models were used. RESULTS: Among the 4,908 study patients, mean (SD) age was 60.9 (14.7) years, 3,095 (62.8%) were male, and 2,552 (52.0%) had obesity. In multivariable models, BMI was not associated with mortality. Higher BMI beginning at 25 kg/m2 was associated with a greater risk of ARDS and AKI-RRT but not thrombosis. There was no clinically significant association between BMI and inflammatory or thrombotic markers. CONCLUSIONS: In critically ill patients with COVID-19, higher BMI was not associated with death or thrombotic events but was associated with a greater risk of ARDS and AKI-RRT. The lack of an association between BMI and circulating biomarkers calls into question the paradigm that obesity contributes to poor outcomes in critically ill patients with COVID-19 by upregulating systemic inflammatory and prothrombotic pathways.