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.

Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) 1 . Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia 2 . We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA-seq on 10 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly-unfolding, spatially limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

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.

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Background/Objectives Older adults commonly face difficult decisions regarding invasive medical treatments near the end of life, including surgical procedures. There is a need for interventions that help physicians, patients and caregivers deliberate about these difficult decisions and make informed choices that reflect patients’ values and goals. Design We designed a communication tool called “Best Case/Worst Case” (BC/WC) based on an established conceptual model of shared decision making. We evaluated the tool with focus groups of seniors (4 groups) and surgeons (2 groups) using modified questions from the Decision Aid Acceptability Scale and the Decisional Conflict Scale. Setting and Participants We recruited 37 adults over age 60 from senior centers and 17 surgeons from academic and private practices in Wisconsin to participate in the study. Measurements We used qualitative content analysis to explore themes and concepts identified by focus group respondents. Results Seniors and surgeons praised the tool for the unambiguous illustration of multiple treatment options, and the clarity gained from presentation of an array of treatment outcomes. Participants noted that the tool provides both an opportunity for in-the-moment, preference-based deliberation about options and a platform for further discussion with other clinicians and loved ones. Seniors worried that the format of the tool was not universally accessible for patients with different educational backgrounds, while surgeons had concerns that the tool was vulnerable to physicians’ subjective biases. Conclusion The BC/WC tool is a novel decision support intervention that may help facilitate difficult decision making for older adults and their physicians when considering invasive, acute medical treatments such as surgery.

Context Older adults often have surgery in the months preceding death, which can initiate post-operative treatments inconsistent with end-of-life values. “Best Case/Worst Case” (BC/WC) is a communication tool designed to promote goal-concordant care during discussions about high-risk surgery. Objective To evaluate a structured training program designed to teach surgeons how to use BC/WC. Methods Twenty-five surgeons from one tertiary-care hospital completed a two-hour training session followed by individual coaching. We audio recorded surgeons using BC/WC with standardized patients and 20 hospitalized patients. Hospitalized patients and their families participated in an open-ended interview 30 to 120 days after enrollment. We used a checklist of 11 BC/WC elements to measure tool fidelity and surgeons completed the Practitioner Opinion Survey to measure acceptability of the tool. We used qualitative analysis to evaluate variability in tool content and to characterize patient and family perceptions of the tool. Results Surgeons completed a median of 10 out of 11 BC/WC elements with both standardized and hospitalized patients (range 5 to 11). We found moderate variability in presentation of treatment options and description of outcomes. Three months after training, 79% of surgeons reported BC/WC is better than their usual approach and 71% endorsed active use of BC/WC in clinical practice. Patients and families found that BC/WC established expectations, provided clarity and facilitated deliberation. Conclusions and Relevance Surgeons can learn to use BC/WC with older patients considering acute high-risk surgical interventions. Surgeons, patients, and family members endorse BC/WC as a strategy to support complex decision making.

Objective To explore high-stakes surgical decision making from the perspective of seniors and surgeons. Background A majority of older chronically ill patients would decline a low-risk procedure if the outcome was severe functional impairment. However, 25 percent of Medicare beneficiaries have surgery in their last three months of life, which may be inconsistent with their preferences. How patients make decisions to have surgery may contribute to this problem of unwanted care. Methods We convened four focus groups at senior centers and two groups of surgeons in Madison and Milwaukee, Wisconsin, where we showed a video about a decision regarding a choice between surgery and palliative care. We used qualitative content analysis to identify themes about communication and explanatory models for end-of-life treatment decisions. Results Seniors(N = 37) and surgeons (N = 17) agreed that maximizing quality of life should guide treatment decisions for older patients. However, when faced with an acute choice between surgery and palliative care, seniors viewed this either as a choice between life and death or a decision about how to die. Although surgeons agreed that very frail patients should not have surgery they held conflicting views about presenting treatment options. Conclusions Seniors and surgeons highly value quality of life but this notion is difficult to incorporate in acute surgical decisions. Some seniors use values to consider a choice between surgery and palliative care, while others view this as a simple choice between life and death. Surgeons acknowledge challenges framing decisions and describe a clinical momentum that promotes surgical intervention.

Many older adults in the United States receive invasive medical care near the end of life, often in an intensive care unit (ICU). However, most older adults report preferences to avoid this type of medical care and to prioritize comfort and quality of life near death. We propose a novel term, "clinical momentum," to describe a systemlevel, latent, previously unrecognized property of clinical care that may contribute to the provision of unwanted care in the ICU. The example of chronic critical illness illustrates how clinical momentum is generated and propagated during the care of patients with prolonged illness. The ICU is an environment that is generally permissive of intervention, and clinical practice norms and patterns of usual care can promote the accumulation of multiple interventions over time. Existing models of medical decision-making in the ICU describe how individual signs, symptoms, or diagnoses automatically lead to intervention, bypassing opportunities to deliberate about the value of an intervention in the context of a patient's likely outcome or treatment preferences. We hypothesize that clinical momentum influences patients, families, and physicians to accept or tolerate ongoing interventions without consideration of likely outcomes, eventually leading to the delivery of unwanted care near the end of life. In the future, a mixed-methods research program could refine the conceptual model of clinical momentum, measure its impact on clinical practice, and interrupt its influence on unwanted care near the end of life.