Acute Respiratory Failure From Early Pandemic COVID-19: Noninvasive Respiratory Support vs Mechanical Ventilation.

BACKGROUND: The optimal strategy for initial respiratory support in patients with respiratory failure associated with COVID-19 is unclear, and the initial strategy may affect outcomes. RESEARCH QUESTION: Which initial respiratory support strategy is associated with improved outcomes in patients with COVID-19 with acute respiratory failure? STUDY DESIGN AND METHODS: All patients with COVID-19 requiring respiratory support and admitted to a large health care network were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (NIRS; noninvasive positive pressure ventilation by facemask or high-flow nasal oxygen) with patients treated initially with invasive mechanical ventilation (IMV). The primary outcome was time to in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths of stay (ICU and hospital), and time to intubation. RESULTS: Nearly one-half of the 2,354 patients (47%) who met inclusion criteria received IMV first, and 53% received initial NIRS. Overall, in-hospital mortality was 38% (37% for IMV and 39% for NIRS). Initial NIRS was associated with an increased hazard of death compared with initial IMV (hazard ratio, 1.42; 95% CI, 1.03-1.94), but also an increased hazard of leaving the hospital sooner that waned with time (noninvasive support by time interaction: hazard ratio, 0.97; 95% CI, 0.95-0.98). INTERPRETATION: Patients with COVID-19 with acute hypoxemic respiratory failure initially treated with NIRS showed an increased hazard of in-hospital death.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Noninvasive respiratory support in the emergency department: Controversies and state-of-the-art recommendations.

Acute respiratory failure is a common reason for emergency department visits and hospital admissions. Diverse underlying physiologic abnormalities lead to unique aspects about the most common causes of acute respiratory failure: acute decompensated heart failure, acute exacerbation of chronic obstructive pulmonary disease, and acute de novo hypoxemic respiratory failure. Noninvasive respiratory support strategies are increasingly used methods to support work of breathing and improve gas exchange abnormalities to improve outcomes relative to conventional oxygen therapy or invasive mechanical ventilation. Noninvasive respiratory support includes noninvasive positive pressure ventilation and nasal high flow, each with unique physiologic mechanisms. This paper will review the physiology of respiratory failure and noninvasive respiratory support modalities and offer data and guideline-driven recommendations in the context of key clinical controversies.

Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: Lessons learned from recent clinical trials.

Cardiac arrest is a leading contributor to morbidity and mortality in the United States. Survival has been historically dependent on high-quality cardiopulmonary resuscitation (CPR) and rapid defibrillation. However, a large percentage of patients remain in refractory cardiac arrest despite adherence to structured advanced cardiac life support algorithms in which these factors are emphasized. Veno-arterial extracorporeal membrane oxygenation is becoming an increasingly used rescue therapy for patients in refractory cardiac arrest to restore oxygen delivery by extracorporeal CPR (ECPR). Recently published clinical trials have provided new insights into ECPR for patients who sustain an outside hospital cardiac arrest (OHCA). In this narrative review, we summarize the rationale for, results of, and remaining questions from these recently published clinical trials. The existing observational data combined with the latest clinical trials suggest ECPR improves mortality in patients in refractory arrest. However, a mixed methods trial is essential to understand the complexity, context, and effectiveness of implementing an ECPR program.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Preoxygenation and Apneic Oxygenation in Emergency Airway Management.

Objective: Preoxygenation during the peri-intubation period is now considered a critical aspect of rapid sequence intubation and an important skill for emergency medicine and critical care providers. Peri-intubation hypoxemia carries significant risk, including cardiac arrest, and care must be taken for appropriate management including through apnea and initiation of laryngoscopy. Appropriate selection of preoxygenation devices should depend on underlying physiology to optimize oxygenation prior to intubation attempts. Methods: A PubMed Medline search. was completed with selection of articles from March 2008 to March 2023 describing various techniques for preoxygenation for intubation in the critical care and operating room setting with pregnant and obese patient populations included. Prehospital and pediatric populations were excluded in this review. Outcomes: This review provides an overview of methods of preoxygenation with their clinical indications as well as methods for determining end points to preoxygenation and apneic oxygenation. An overview of approaches to preoxygenation was included for patients considered to have a physiologically difficult airway and obese and pregnant patient populations.

High-flow nasal cannula vs non-invasive ventilation in acute hypoxia: Propensity score matched study.

RATIONALE: The optimal treatment for early hypoxemic respiratory failure is unclear, and both high-flow nasal cannula and non-invasive ventilation are used. Determining clinically relevant outcomes for evaluating non-invasive respiratory support modalities remains a challenge. OBJECTIVES: To compare the effectiveness of initial treatment with high-flow nasal cannula versus non-invasive ventilation for acute hypoxemic respiratory failure. METHODS: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with high-flow nasal cannula or non-invasive ventilation within 24 hours of Emergency Department arrival (1/2018-12/2022). We matched patients 1:1 using a propensity score for odds of receiving non-invasive ventilation. The primary outcome was major adverse pulmonary events (28-day mortality, ventilator-free days, non-invasive respiratory support hours) calculated using a Win Ratio. MEASUREMENTS AND MAIN RESULTS: 1,265 patients met inclusion criteria. 795 (62.8%) received high-flow oxygen and 470 (37.2%) received non-invasive ventilation. We propensity score matched 736/1,265 (58.2%) patients. There was no difference between non-invasive ventilation vs high-flow nasal cannula in 28-day mortality (17.7% vs 23.1%, p=0.08) or ventilator-free days (median [Interquartile Range]: 28 [25, 28] vs 28 [13, 28], p=0.50), but patients on non-invasive ventilation required treatment for fewer hours (median 7 vs 13, p< 0.001). Win Ratio for composite major adverse pulmonary events favored non-invasive ventilation (1.26, 95%CI 1.06-1.49, p< 0.001). CONCLUSIONS: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with non-invasive ventilation was superior to high-flow nasal cannula for major pulmonary adverse events. Evaluation of composite outcomes is important in the assessment of respiratory support modalities.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Comparison of Force During the Endotracheal Intubation of Commercial Simulation Manikins.

Background  Medical simulation allows clinicians to safely practice the procedural skill of endotracheal intubation. Applied force to oropharyngeal structures increases the risk of patient harm, and video laryngoscopy (VL) requires less force to obtain a glottic view. It is unknown how much force is required to obtain a glottic view using commercially available simulation manikins and if variability exists. This study compares laryngoscopy force for a modified Cormack-Lehane (CL) grade I view in both normal and difficult airway scenarios between three commercially available simulation manikins. Methods Experienced clinicians (≥2 years experience) were recruited to participate from critical care, emergency medicine, and anesthesia specialties. A C-MAC size 3 VL blade was equipped with five force resistor reading (FSR) sensors (four concave surfaces, one convex), measuring resistance (Ohms) in response to applied pressure (1-100 Newtons). The study occurred in a university simulation lab. Using a randomized sequence, 49 physicians performed intubations on three manikins (Laerdal SimMan 3GPlus, Gaumard Hal S3201, CAE Apollo) in normal and difficult airway scenarios. The outcomes were sensor mean pressure, peak force, and CL grade. Summary statistics were calculated. Generalized estimating equations (GEEs) conducted for both scenarios assessed changes in pressure measured in three manikins while accounting for correlated responses of individuals assigned in random order. Paired t-test assessed for the in-manikin difference between scenarios. STATA/BE v17 (R) was used for analysis; results interpreted at type I error alpha is 0.05.  Results Participants included 49 experienced clinicians. Mean years' experience was 4(±6.6); median prior intubations were 80 (IQR 50-400). Mean individual sensor pressure varied within scenarios depending on manikin (p<0.001). Higher mean forces were used in difficult scenarios (603.4±128.9, 611.1±101.4, 467.5±72.4 FSR) than normal (462.5±121.9, 596.0±90.5, 290.6±63.2 FSR) for each manikin (p<0.001). All manikins required more peak force in the difficult scenario (p<0.03). The highest mean forces (Laerdal, CAE, difficult scenario) were associated with the higher frequency of grade 2A views (p<0.001). The Gaumard manikin was rated most realistic in terms of force required to intubate. Conclusion Commercially available high-fidelity manikins had significant variability in laryngoscopy force in both normal and difficult airway scenarios. In difficult airway scenarios, significant variability existed in CL grade between manikin brands. Experienced clinicians rated Gaumard Hal as the most realistic force applied during endotracheal intubation.

Managed critical care: impact of remote decision-making on patient outcomes.

OBJECTIVES: Tele-intensive care unit (tele-ICU) use has become increasingly common as an extension of bedside care for critically ill patients. The objective of this work was to illustrate the degree of tele-ICU involvement in critical care processes and evaluate the impact of tele-ICU decision-making authority. STUDY DESIGN: Previous studies examining tele-ICU impact on patient outcomes do not sufficiently account for the extent of decision-making authority between remote and bedside providers. In this study, we examine patient outcomes with respect to different levels of remote intervention. METHODS: Analysis and summary statistics were generated to characterize demographics and patient outcomes across different levels of tele-ICU intervention for 82,049 critically ill patients. Multivariate logistic regression was used to evaluate odds of mortality, readmission, and likelihood of patients being assigned to a particular remote intervention category. RESULTS: Managing (vs consulting) physician type influenced the level of remote intervention (adjusted odds ratio [AOR], 2.42). A higher level of tele-ICU intervention was a significant factor for patient mortality (AOR, 1.25). Female sex (AOR, 1.05), illness severity (AOR, 1.01), and higher tele-ICU intervention level (AOR, 1.13) increased odds of ICU readmission, whereas length of stay in number of days (AOR, 0.93) and consulting (vs managing) physician type (AOR, 0.79) decreased readmission odds. CONCLUSIONS: This study's findings suggest that higher levels of tele-ICU intervention do not negatively affect patient outcomes. Our results are a step toward understanding tele-ICU impact on patient outcomes by accounting for extent of decision-making authority, and they suggest that the level of remote intervention may reflect patient severity. Further research using more granular data is needed to better understand assignment of intervention category and how variable levels of authority affect clinical decision-making in tele-ICU settings.

The impact of intravenous dodecafluoropentane on a murine model of acute lung injury.

INTRODUCTION: Intravenous oxygen therapeutics present an appealing option for improving arterial oxygenation in patients with acute hypoxemic respiratory failure, while limiting iatrogenic injury from conventional respiratory management. METHODS: We used an established two-hit murine model of acute lung injury (ARDS/VILI) to evaluate the effect of intravenous dodecafluoropentane (DDFPe) on oxygen saturation and bronchoalveolar lavage cell counts and protein levels. Twenty hours after challenge with intratracheal lipopolysaccharide, mice were intubated and ventilated with high tidal volumes (4 h) to produce acute lung injury. DDFPe (0.6 mL/kg) or saline was administered by IV bolus injection at the initiation of mechanical ventilation and again at 2 h. Oxygen saturation was measured every 15 min. Bronchoalveolar lavage was performed at the conclusion of the experiment. RESULTS: The two-hit ARDS/VILI model produced substantial inflammatory acute lung injury reflected by markedly increased bronchoalveolar lavage (BAL) cell counts compared to BAL cell counts in spontaneous breathing controls (5.29 ± 1.50 × 10-6 vs 0.74 ± 0.014 × 10-6 cells/mL) Similarly, BAL protein levels were markedly elevated in ARDS/VILI-challenged mice compared with spontaneous breathing controls (1109.27 ± 223.80 vs 129.6 ± 9.75 ng/mL). We fit a linear mixed effects model that showed a significant difference in oxygen saturation over time between DDFPe-treated mice and saline-treated mice, with separation starting after the 2-h injection. DDFPe-treated ARDS/VILI-challenged mice also exhibited significant reductions in BAL cell counts but not in BAL protein. CONCLUSION: DDFPe improves oxygen saturation in a murine model of ARDS/VILI injury with the potential for serving as an intravenous oxygen therapeutic.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

T-cell cellular stress and reticulocyte signatures, but not loss of naïve T lymphocytes, characterize severe COVID-19 in older adults.

In children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old. To understand age-specific immune pathobiology of COVID-19, we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable. We found that reticulocyte numbers and peripheral blood transcriptional signatures robustly correlated with disease severity. By contrast, decreased numbers and proportion of naïve T-cells, reported previously as a COVID-19 severity risk factor, were found to be general features of aging and not of COVID-19 severity, as they readily occurred in older participants experiencing only mild or no disease at all. Single-cell transcriptional signatures across age and severity groups showed that severe but not moderate/mild COVID-19 causes cell stress response in different T-cell populations, and some of that stress was unique to old severe participants, suggesting that in severe disease of older adults, these defenders of the organism may be disabled from performing immune protection. These findings shed new light on interactions between age and disease severity in COVID-19.

Predicting Failure of Noninvasive Respiratory Support Using Deep Recurrent Learning.

BACKGROUND: Noninvasive respiratory support (NRS) is increasingly used to support patients with acute respiratory failure. However, noninvasive support failure may worsen outcomes compared to primary support with invasive mechanical ventilation. Therefore, there is a need to identify patients where NRS is failing so that treatment can be reassessed and adjusted. The objective of this study was to develop and evaluate 3 recurrent neural network (RNN) models to predict NRS failure. METHODS: This was a cross-sectional observational study to evaluate the ability of deep RNN models (long short-term memory [LSTM], gated recurrent unit [GRU]), and GRU with trainable decay) to predict failure of NRS. Data were extracted from electronic health records from all adult (≥ 18 y) patient records requiring any type of oxygen therapy or mechanical ventilation between November 1, 2013-September 30, 2020, across 46 ICUs in the Southwest United States in a single health care network. Input variables for each model included serum chloride, creatinine, albumin, breathing frequency, heart rate, SpO2 , FIO2 , arterial oxygen saturation (SaO2 ), and 2 measurements each (point-of-care and laboratory measurement) of PaO2 and partial pressure of arterial oxygen from an arterial blood gas. RESULTS: Time series data from electronic health records were available for 22,075 subjects. The highest accuracy and area under the receiver operating characteristic curve were for the LSTM model (94.04% and 0.9636, respectively). Accurate predictions were made 12 h after ICU admission, and performance remained high well in advance of NRS failure. CONCLUSIONS: RNN models using routinely collected time series data can accurately predict NRS failure well before intubation. This lead time may provide an opportunity to intervene to optimize patient outcomes.

Computable Phenotypes for Post-acute sequelae of SARS-CoV-2: A National COVID Cohort Collaborative Analysis.

Post-acute sequelae of SARS-CoV-2 (PASC) is an increasingly recognized yet incompletely understood public health concern. Several studies have examined various ways to phenotype PASC to better characterize this heterogeneous condition. However, many gaps in PASC phenotyping research exist, including a lack of the following: 1) standardized definitions for PASC based on symptomatology; 2) generalizable and reproducible phenotyping heuristics and meta-heuristics; and 3) phenotypes based on both COVID-19 severity and symptom duration. In this study, we defined computable phenotypes (or heuristics) and meta-heuristics for PASC phenotypes based on COVID-19 severity and symptom duration. We also developed a symptom profile for PASC based on a common data standard. We identified four phenotypes based on COVID-19 severity (mild vs. moderate/severe) and duration of PASC symptoms (subacute vs. chronic). The symptoms groups with the highest frequency among phenotypes were cardiovascular and neuropsychiatric with each phenotype characterized by a different set of symptoms.

Noninvasive vs Invasive Respiratory Support for Patients with Acute Hypoxemic Respiratory Failure.

Rationale: Noninvasive respiratory support modalities are common alternatives to mechanical ventilation for patients with early acute hypoxemic respiratory failure. These modalities include noninvasive positive pressure ventilation, using either continuous or bilevel positive airway pressure, and nasal high flow using a high flow nasal cannula system. However, outcomes data historically compare noninvasive respiratory support to conventional oxygen rather than to mechanical ventilation. Objectives: The goal of this study was to compare the outcomes of in-hospital death and alive discharge in patients with acute hypoxemic respiratory failure when treated initially with noninvasive respiratory support compared to patients treated initially with invasive mechanical ventilation. Methods: We used a validated phenotyping algorithm to classify all patients with eligible International Classification of Diseases codes at a large healthcare network between January 1, 2018 and December 31, 2019 into noninvasive respiratory support and invasive mechanical ventilation cohorts. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders, with estimated cumulative incidence curves. Secondary outcomes included time-to-hospital discharge alive. A secondary analysis was conducted to examine potential differences between noninvasive positive pressure ventilation and nasal high flow. Results: During the study period, 3177 patients met inclusion criteria (40% invasive mechanical ventilation, 60% noninvasive respiratory support). Initial noninvasive respiratory support was not associated with a decreased hazard of in-hospital death (HR: 0.65, 95% CI: 0.35 - 1.2), but was associated with an increased hazard of discharge alive (HR: 2.26, 95% CI: 1.92 - 2.67). In-hospital death varied between the nasal high flow (HR 3.27, 95% CI: 1.43 - 7.45) and noninvasive positive pressure ventilation (HR 0.52, 95% CI 0.25 - 1.07), but both were associated with increased likelihood of discharge alive (nasal high flow HR 2.12, 95 CI: 1.25 - 3.57; noninvasive positive pressure ventilation HR 2.29, 95% CI: 1.92 - 2.74). Conclusion: These observational data from a large healthcare network show that noninvasive respiratory support is not associated with reduced hazards of in-hospital death but is associated with hospital discharge alive. There are also potential differences between the noninvasive respiratory support modalities.