Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Functional, imaging, and respiratory evaluation (FIRE) of patients post-hospitalization for COVID-19: protocol for a pilot observational study.

INTRODUCTION: We describe a protocol for FIRE CORAL, an observational cohort study that examines the recovery from COVID-19 disease following acute hospitalization with an emphasis on functional, imaging, and respiratory evaluation. METHODS AND ANALYSIS: FIRE CORAL is a multicenter prospective cohort study of participants recovering from COVID-19 disease with in-person follow-up for functional and pulmonary phenotyping conducted by the National Heart, Lung and Blood Institute (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. FIRE CORAL will include a subset of participants enrolled in Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study (BLUE CORAL), an NHLBI-funded prospective cohort study describing the clinical characteristics, treatments, biology, and outcomes of hospitalized patients with COVID-19 across the PETAL Network. FIRE CORAL consists of a battery of in-person assessments objectively measuring pulmonary function, abnormalities on lung imaging, physical functional status, and biospecimen analyses. Participants will attend and perform initial in-person testing at 3 to 9 months after hospitalization. The primary objective of the study is to determine the feasibility of longitudinal assessments investigating multiple domains of recovery from COVID-19. Secondarily, we will perform descriptive statistics, including the prevalence and characterization of abnormalities on pulmonary function, chest imaging, and functional status. We will also identify potential clinical and biologic factors that predict recovery or the occurrence of persistent impairment of pulmonary function, chest imaging, and functional status. ETHICS AND DISSEMINATION: FIRE CORAL is approved via the Vanderbilt University central institutional review board (IRB) and via reliance agreement with the site IRBs. Results will be disseminated via the writing group for the protocol committee and reviewed by the PETAL Network publications committee prior to publication. Data obtained via the study will subsequently be made publicly available via NHLBI's biorepository. STRENGTHS AND LIMITATIONS OF THE STUDY: Strengths: First US-based multicenter cohort of pulmonary and functional outcomes in patients previously hospitalized for COVID-19 infection Longitudinal biospecimen measurement allowing for biologic phenotyping of abnormalities Geographically diverse cohort allowing for a more generalizable understanding of post-COVID pulmonary sequela Limitations: Selected cohort given proximity to a participating center Small cohort which may be underpowered to identify small changes in pulmonary function.

Characteristics and Outcomes of US Patients Hospitalized With COVID-19.

BACKGROUND: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. OBJECTIVE: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. METHODS: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. RESULTS: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. CONCLUSIONS: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

Continuing Cardiopulmonary Symptoms, Disability, and Financial Toxicity 1 Month After Hospitalization for Third-Wave COVID-19: Early Results From a US Nationwide Cohort.

BACKGROUND: Patients discharged after COVID-19 report ongoing needs. OBJECTIVES: To measure incident symptoms after COVID-19 hospitalization. DESIGN, SETTING, AND PARTICIPANTS: Preplanned early look at 1-month follow-up surveys from patients hospitalized August 2020 to January 2021 in NHLBI PETAL Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. English- or Spanish-speaking hospitalized adults without substantial pre-COVID-19 disability with a positive molecular test for SARS-CoV-2. RESULTS: Overall, 253 patients were hospitalized for a median of 5 days (interquartile range [IQR], 3-8), and had a median age of 60 years (IQR, 45-68). By race/ethnicity, 136 (53.8%) were non-Hispanic White, 23 (9.1%) were non-Hispanic Black, and 83 (32.8%) were Hispanic. Most (139 [54.9%]) reported a new or worsened cardiopulmonary symptom, and 16% (n = 39) reported new or increased oxygen use; 213 (84.2%) patients reported not feeling fully back to their pre-COVID-19 level of functioning. New limitations in activities of daily living were present in 130 (52.8%) patients. Financial toxicities, including job loss or change (49 [19.8%]), having a loved one take time off (93 [37.8%]), and using up one's savings (58 [23.2%]), were common. Longer lengths of hospital stay were associated with greater odds of 1-month cardiopulmonary symptoms (adjusted odds ratio [aOR], 1.82 per additional week in the hospital; 95% CI, 1.11-2.98) and new disability (aOR, 2.06; 95% CI, 1.21-3.53). There were not uniform demographic patterns of association. LIMITATIONS: We prioritized patients' reports of their own incident problems over objective testing. CONCLUSION: Patients who survived COVID-19 in the United States during late 2020/early 2021 still faced new burdens 1 month after hospital discharge.

Variation in Initial U.S. Hospital Responses to the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: The coronavirus disease 2019 pandemic has strained many healthcare systems. In response, U.S. hospitals altered their care delivery systems, but there are few data regarding specific structural changes. Understanding these changes is important to guide interpretation of outcomes and inform pandemic preparedness. We sought to characterize emergency responses across hospitals in the United States over time and in the context of local case rates early in the coronavirus disease 2019 pandemic. DESIGN: We surveyed hospitals from a national acute care trials group regarding operational and structural changes made in response to the coronavirus disease 2019 pandemic from January to August 2020. We collected prepandemic characteristics and changes to hospital system, space, staffing, and equipment during the pandemic. We compared the timing of these changes with county-level coronavirus disease 2019 case rates. SETTING AND PARTICIPANTS: U.S. hospitals participating in the Prevention and Early Treatment of Acute Lung Injury Network Coronavirus Disease 2019 Observational study. Site investigators at each hospital collected local data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-five sites participated (94% response rate). System-level changes (incident command activation and elective procedure cancellation) occurred at nearly all sites, preceding rises in local case rates. The peak inpatient census during the pandemic was greater than the prior hospital bed capacity in 57% of sites with notable regional variation. Nearly half (49%) expanded ward capacity, and 63% expanded ICU capacity, with nearly all bed expansion achieved through repurposing of clinical spaces. Two-thirds of sites adapted staffing to care for patients with coronavirus disease 2019, with 48% implementing tiered staffing models, 49% adding temporary physicians, nurses, or respiratory therapists, and 30% changing the ratios of physicians or nurses to patients. CONCLUSIONS: The coronavirus disease 2019 pandemic prompted widespread system-level changes, but front-line clinical care varied widely according to specific hospital needs and infrastructure. Linking operational changes to care delivery processes is a necessary step to understand the impact of the coronavirus disease 2019 pandemic on patient outcomes.

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

BACKGROUND: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).

Low tidal volume ventilation use remains low in patients with acute respiratory distress syndrome at a single center.

PURPOSE: Low tidal volume ventilation (LTVV) reduces mortality in acute respiratory distress syndrome (ARDS) patients. Understanding local barriers to LTVV use at a former ARDS Network hospital may provide new insight to improve LTVV implementation. METHODS: A cohort of 214 randomly selected adults met the Berlin definition of ARDS at Harborview Medical Center between 2008 and 2012. The primary outcome was the receipt of LTVV (tidal volume of ≤6.5mL/kg predicted body weight) within 48h of ARDS onset. We constructed a multivariable logistic regression model to identify factors associated with the outcome. RESULTS: Only 27% of patients received tidal volumes of ≤6.5mL/kg PBW within 48h of ARDS onset. Increasing plateau pressure (OR 1.11; 95% CI 1.03 to 1.19; p-value<0.01) was positively associated with LTVV use while increasing PaO2:FIO2 ratio was negatively associated (OR 0.75; 95% CI 0.57 to 0.98; p-value 0.03). Physicians documented an ARDS diagnosis in only 21% of the cohort. Neither patient height nor gender was associated with LTVV use. CONCLUSIONS: Most ARDS patients did not receive LTVV despite implementation of a protocol. ARDS was also recognized in a minority of patients, suggesting an opportunity for improvement of care.

Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome.

The Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial is a multicenter, randomized trial designed to assess the efficacy and safety of early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome. This document provides background for interpretation of the trial results, and highlights unique design approaches that may inform future trials of acute illness. We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network, provide the trial methodology using the Consolidated Standards of Reporting Trials framework, and discuss key design challenges and their resolution. Four key design issues proved challenging-feasibility, choice of sedation depth in the control group, impact of emphasizing early treatment on enrollment criteria and protocol execution, and choice of positive end-expiratory pressure strategy. We used literature, an iterative consensus model, and internal surveys of current practice to inform design choice. ROSE will provide definitive, Consolidated Standards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome. Our multidisciplinary approach to trial design may be of use to other trials of acute illness. Clinical trial registered with www.clinicaltrials.gov (NCT02509078).

Improving ICU-Based Palliative Care Delivery: A Multicenter, Multidisciplinary Survey of Critical Care Clinician Attitudes and Beliefs.

OBJECTIVE: Addressing the quality gap in ICU-based palliative care is limited by uncertainty about acceptable models of collaborative specialist and generalist care. Therefore, we characterized the attitudes of physicians and nurses about palliative care delivery in an ICU environment. DESIGN: Mixed-methods study. SETTING: Medical and surgical ICUs at three large academic hospitals. PARTICIPANTS: Three hundred three nurses, intensivists, and advanced practice providers. MEASUREMENTS AND MAIN RESULTS: Clinicians completed written surveys that assessed attitudes about specialist palliative care presence and integration into the ICU setting, as well as acceptability of 23 published palliative care prompts (triggers) for specialist consultation. Most (n = 225; 75%) reported that palliative care consultation was underutilized. Prompting consideration of eligibility for specialist consultation by electronic health record searches for triggers was most preferred (n = 123; 41%); only 17 of them (6%) felt current processes were adequate. The most acceptable specialist triggers were metastatic malignancy, unrealistic goals of care, end of life decision making, and persistent organ failure. Advanced age, length of stay, and duration of life support were the least acceptable. Screening led by either specialists or ICU teams was equally preferred. Central themes derived from qualitative analysis of 65 written responses to open-ended items included concerns about the roles of physicians and nurses, implementation, and impact on ICU team-family relationships. CONCLUSIONS: Integration of palliative care specialists in the ICU is broadly acceptable and desired. However, the most commonly used current triggers for prompting specialist consultation were among the least well accepted, while more favorable triggers are difficult to abstract from electronic health record systems. There is also disagreement about the role of ICU nurses in palliative care delivery. These findings provide important guidance to the development of collaborative care models for the ICU setting.

Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States.

OBJECTIVE: Early mobility in mechanically ventilated patients is safe, feasible, and may improve functional outcomes. We sought to determine the prevalence and character of mobility for ICU patients with acute respiratory failure in U.S. ICUs. DESIGN: Two-day cross-sectional point prevalence study. SETTING: Forty-two ICUs across 17 Acute Respiratory Distress Syndrome Network hospitals. PATIENTS: Adult patients (≥ 18 yr old) with acute respiratory failure requiring mechanical ventilation. INTERVENTIONS: We defined therapist-provided mobility as the proportion of patient-days with any physical or occupational therapy-provided mobility event. Hierarchical regression models were used to identify predictors of out-of-bed mobility. MEASUREMENTS AND MAIN RESULTS: Hospitals contributed 770 patient-days of data. Patients received mechanical ventilation on 73% of the patient-days mostly (n = 432; 56%) ventilated via an endotracheal tube. The prevalence of physical therapy/occupational therapy-provided mobility was 32% (247/770), with a significantly higher proportion of nonmechanically ventilated patients receiving physical therapy/occupational therapy (48% vs 26%; p ≤ 0.001). Patients on mechanical ventilation achieved out-of-bed mobility on 16% (n = 90) of the total patient-days. Physical therapy/occupational therapy involvement in mobility events was strongly associated with progression to out-of-bed mobility (odds ratio, 29.1; CI, 15.1-56.3; p ≤ 0.001). Presence of an endotracheal tube and delirium were negatively associated with out-of-bed mobility. CONCLUSIONS: In a cohort of hospitals caring for acute respiratory failure patients, physical therapy/occupational therapy-provided mobility was infrequent. Physical therapy/occupational therapy involvement in mobility was strongly predictive of achieving greater mobility levels in patients with respiratory failure. Mechanical ventilation via an endotracheal tube and delirium are important predictors of mobility progression.

A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury.

OBJECTIVES: Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought to determine whether enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with acute lung injury. DESIGN: Phase II randomized controlled trial. SETTING: Five North American medical centers. PATIENTS: Mechanically ventilated patients with acute lung injury ≥18 yrs of age. INTERVENTIONS: Subjects were randomized to receive enteral fish oil (9.75 g eicosapentaenoic acid and 6.75 g docosahexanoic acid daily) or saline placebo for up to 14 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid and blood were collected at baseline (day 0), day 4 ± 1, and day 8 ± 1. The primary end point was bronchoalveolar lavage fluid interleukin-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum eicosapentaenoic acid concentration (p < .0001). However, there was no significant difference in the change in bronchoalveolar lavage fluid interleukin-8 from baseline to day 4 (p = .37) or day 8 (p = .55) between treatment arms. There were no appreciable improvements in other bronchoalveolar lavage fluid or plasma biomarkers in the fish oil group compared with the control group. Similarly, organ failure score, ventilator-free days, intensive care unit-free days, and 60-day mortality did not differ between the groups. CONCLUSIONS: Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with acute lung injury, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof-of-concept studies evaluating new treatments for acute lung injury.