Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Sounding the Alarm: What Clinicians Need to Know about Physical, Emotional, and Cognitive Recovery After Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: We summarize the existing data on the occurrence of physical, emotional, and cognitive dysfunction associated with postintensive care syndrome (PICS) in adult survivors of venoarterial extracorporeal membrane oxygenation (VA-ECMO). DATA SOURCES: MEDLINE, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched. STUDY SELECTION: Peer-reviewed studies of adults receiving VA-ECMO for any reason with at least one measure of health-related quality of life outcomes or PICS at long-term follow-up of at least 6 months were included. DATA EXTRACTION: The participant demographics and baseline characteristics, in-hospital outcomes, long-term health outcomes, quality of life outcome measures, and prevalence of PICS were extracted. DATA SYNTHESIS: Twenty-seven studies met inclusion criteria encompassing 3,271 patients who were treated with VA-ECMO. The studies were limited to single- or two-center studies. Outcomes variables and follow-up time points evaluated were widely heterogeneous which limits comprehensive analysis of PICS after VA-ECMO. In general, the longer-term PICS-related outcomes of survivors of VA-ECMO were worse than the general population, and approaching that of patients with chronic disease. Available studies identified high rates of abnormal 6-minute walk distance, depression, anxiety, and posttraumatic stress disorder that persisted for years. Half or fewer survivors return to work years after discharge. Only 2 of 27 studies examined cognitive outcomes and no studies evaluated cognitive dysfunction within the first year of recovery. No studies evaluated the impact of targeted interventions on these outcomes. CONCLUSIONS: Survivors of VA-ECMO represent a population of critically ill patients at high risk for deficits in physical, emotional, and cognitive function related to PICS. This systematic review highlights the alarming reality that PICS and in particular, neurocognitive outcomes, in survivors of VA-ECMO are understudied, underrecognized, and thus likely undertreated. These results underscore the imperative that we look beyond survival to focus on understanding the burden of survivorship with the goal of optimizing recovery and outcomes after these life-saving interventions. Future prospective, multicenter, longitudinal studies in recovery after VA-ECMO are justified.

Rehabilitation Therapy Allocation and Changes in Physical Function Among Patients Hospitalized Due to COVID-19: A Retrospective Cohort Analysis.

OBJECTIVE: Limited staffing and initial transmission concerns have limited rehabilitation services during the COVID-19 pandemic. The purpose of this analysis was to determine the associations between Activity Measure for Post-Acute Care (AM-PAC) mobility categories and allocation of rehabilitation, and in-hospital AM-PAC score change and receipt of rehabilitation services for patients with COVID-19. METHODS: This was a retrospective cohort study of electronic health record data from 1 urban hospital, including adults with a COVID-19 diagnosis, admitted August 2020 to April 2021. Patients were stratified by level of medical care (intensive care unit [ICU] and floor). Therapy allocation (referral for rehabilitation, receipt of rehabilitation, and visit frequency) was the primary outcome; change in AM-PAC score was secondary. AM-PAC Basic Mobility categories (None [21-24], Minimum [18-21], Moderate [10-17], and Maximum [6-9]) were the main predictor variable. Primary analysis included logistic and linear regression, adjusted for covariates. RESULTS: A total of 1397 patients (ICU: n = 360; floor: n = 1037) were included. AM-PAC mobility category was associated with therapy allocation outcomes for floor but not patients in the ICU: the Moderate category had greater adjusted odds of referral (adjusted odds ratio [aOR] = 10.88; 95% CI = 5.71-21.91), receipt of at least 1 visit (aOR = 3.45; 95% CI = 1.51-8.55), and visit frequency (percentage mean difference) (aOR = 42.14; 95% CI = 12.45-79.67). The secondary outcome of AM-PAC score improvement was highest for patients in the ICU who were given at least 1 rehabilitation therapy visit (aOR = 5.31; 95% CI = 1.90-15.52). CONCLUSION: AM-PAC mobility categories were associated with rehabilitation allocation outcomes for floor patients. AM-PAC score improvement was highest among patients requiring ICU-level care with at least 1 rehabilitation therapy visit. IMPACT: Use of AM-PAC Basic Mobility categories may help improve decisions for rehabilitation therapy allocation among patients who do not require critical care, particularly during times of limited resources.

Using Wearable Technology to Quantify Physical Activity Recovery: Secondary Report From the AFTER (App-Facilitated Tele-Rehabilitation) Program for COVID-19 Survivors Randomized Study.

BACKGROUND: Knowledge on physical activity recovery after COVID-19 survival is limited. The AFTER (App-Facilitated Tele-Rehabilitation) program for COVID-19 survivors randomized participants, following hospital discharge, to either education and unstructured physical activity or a telerehabilitation program. Step count data were collected as a secondary outcome, and we found no significant differences in total step count trajectories between groups at 6 weeks. Further step count data were not analyzed. OBJECTIVE: The purpose of this analysis was to examine step count trajectories and correlates among all participants (combined into a single group) across the 12-week study period. METHODS: Linear mixed models with random effects were used to model daily steps over the number of study days. Models with 0, 1, and 2 inflection points were considered, and the final model was selected based on the highest log-likelihood value. RESULTS: Participants included 44 adults (41 with available Fitbit [Fitbit LLC] data). Initially, step counts increased by an average of 930 (95% CI 547-1312; P<.001) steps per week, culminating in an average daily step count of 7658 (95% CI 6257-9059; P<.001) at the end of week 3. During the remaining 9 weeks of the study, weekly step counts increased by an average of 67 (95% CI -30 to 163; P<.001) steps per week, resulting in a final estimate of 8258 (95% CI 6933-9584; P<.001) steps. CONCLUSIONS: Participants showed a marked improvement in daily step counts during the first 3 weeks of the study, followed by more gradual improvement in the remaining 9 weeks. Physical activity data and step count recovery trajectories may be considered surrogates for physiological recovery, although further research is needed to examine this relationship. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663945; https://tinyurl.com/2p969ced.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.

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.

Predictors of adverse outcomes in aged patients critically ill with COVID-19: a retrospective study.

Older patients represent an inordinate proportion of intensive care unit (ICU) admissions and ICU mortality associated with coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examine 198 patients, aged 18 years or older, admitted to the ICU from March to June 2020. We aim to understand the relationships between age, number of comorbidities, and independent living prior to admission on outcomes of mortality, length of stay, renal failure, respiratory failure, and shock. In this cohort, we find that overall mortality was associated with respiratory failure severity (for every decrease of P:F by 50, odds ratio (OR) 2.98 (1.65-6.08)), acute renal failure (OR 4.61 (1.2-19.7)), and age 65 or greater (OR: 3.7 (1.86-7.36)). Surprisingly, increasing age was associated with less severe respiratory failure (R = 0.22, p < 0.01). When adjusting for pre-existing chronic kidney disease, age was not associated with development of acute kidney injury (OR: 1.01 (0.99-1.03)). While chronologic age is associated with mortality, it is not associated independently with severe end organ damage. This is consistent with growing evidence suggesting that a complex interplay between multimorbidity, immunosenescence, and physiologic age is primarily responsible for the vulnerability to COVID-19.

Impact of Alcohol Misuse on Requirements for Critical Care Services and Development of Hospital Delirium in Patients With COVID-19 pneumonia.

Alcohol misuse has been associated with increased morbidity in the setting of pulmonary infections, including the need for critical care resource utilization and development of delirium. How alcohol misuse impacts morbidity and outcomes among patients admitted with COVID-19 pneumonia is not well described. We sought to determine if alcohol misuse was associated with an increased need for critical care resources and development of delirium among patients hospitalized with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Twelve University of Colorado hospitals between March 2020 and April 2021. PATIENTS: Adults with a COVID-19 diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was admission to the ICU. Secondary outcomes included need for mechanical ventilation, development of delirium, and in-hospital mortality. Alcohol misuse was defined by International Classification of Diseases, 10th Revision codes. Of 5,979 patients hospitalized with COVID-19, 26% required ICU admission and 15.4% required mechanical ventilation. Delirium developed in 4.5% and 10.5% died during hospitalization. Alcohol misuse was identified in 4%. In analyses adjusted for age, sex, body mass index, diabetes, and liver disease, alcohol misuse was associated with increased odds of ICU admission (adjusted odds ratio [aOR], 1.46; p < 0.01), mechanical ventilation (aOR, 1.43; p = 0.03), and delirium (aOR, 5.55; p < 0.01) compared with patients without misuse. Mortality rates were not associated with alcohol misuse alone, although the presence of both alcohol misuse and in-hospital delirium significantly increased odds of in-hospital death (aOR, 2.60; p = 0.04). CONCLUSIONS: Among patients hospitalized with COVID-19, alcohol misuse was associated with increased utilization of critical care resources including ICU admission and mechanical ventilation. Delirium was an important modifiable risk factor associated with worse outcomes in hospitalized patients with alcohol misuse, including increased odds of death.

Early posthospitalization recovery after extracorporeal membrane oxygenation in survivors of COVID-19.

OBJECTIVE: We sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge. METHODS: Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. RESULTS: Two hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar. CONCLUSIONS: Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of 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.

Safety, feasibility and initial efficacy of an app-facilitated telerehabilitation (AFTER) programme for COVID-19 survivors: a pilot randomised study.

OBJECTIVES: Determine the safety, feasibility and initial efficacy of a multicomponent telerehabilitation programme for COVID-19 survivors. DESIGN: Pilot randomised feasibility study. SETTING: In-home telerehabilitation. PARTICIPANTS: 44 participants (21 female, mean age 52 years) discharged home following hospitalisation with COVID-19 (with and without intensive care unit (ICU) stay). INTERVENTIONS: Participants were block randomised 2:1 to receive 12 individual biobehaviourally informed, app-facilitated, multicomponent telerehabilitation sessions with a licenced physical therapist (n=29) or to a control group (n=15) consisting of education on exercise and COVID-19 recovery trajectory, physical activity and vitals monitoring, and weekly check-ins with study staff. Interventions were 100% remote and occurred over 12 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was feasibility, including safety and session adherence. Secondary outcomes included preliminary efficacy outcomes including tests of function and balance; patient-reported outcome measures; a cognitive assessment; and average daily step count. The 30 s chair stand test was the main secondary (efficacy) outcome. RESULTS: No adverse events (AEs) occurred during testing or in telerehabilitation sessions; 38% (11/29) of the intervention group compared with 60% (9/15) of the control group experienced an AE (p=0.21), most of which were minor, over the course of the 12-week study. 27 of 29 participants (93%; 95% CI 77% to 99%) receiving the intervention attended ≥75% of sessions. Both groups demonstrated clinically meaningful improvement in secondary outcomes with no statistically significant differences between groups. CONCLUSION: Fully remote telerehabilitation was safe, feasible, had high adherence for COVID-19 recovery, and may apply to other medically complex patients including those with barriers to access care. This pilot study was designed to evaluate feasibility; further efficacy evaluation is needed. TRIAL REGISTRATION NUMBER: NCT04663945.

Medication prescribing for alcohol use disorders during alcohol-related encounters in a Colorado regional healthcare system.

RATIONALE: Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders (AUD) receive MAUD across care settings. The epidemiology of MAUD prescribing in the acute care setting is incompletely described. We hypothesized that MAUD would be under prescribed in inpatient acute care hospital settings compared to the outpatient, emergency department (ED), and inpatient substance use treatment settings. METHODS: We evaluated electronic health record (EHR) data from adult patients with an International Classification of Diseases, 10th revision (ICD-10) alcohol-related diagnosis in the University of Colorado Health (UCHealth) system between January 1, 2016 and 31 December, 2019. Data from patients with an ICD-10 diagnosis code for opioid use disorder and those receiving MAUD prior to their first alcohol-related episode were excluded. The primary outcome was prescribing of MAUD, defined by prescription of naltrexone, acamprosate, and/or disulfiram. We performed bivariate and multivariate analyses to identify independent predictors of MAUD prescribing at UCHealth. RESULTS: We identified 48,421 unique patients with 136,205 alcohol-related encounters at UCHealth. Encounters occurred in the ED (42%), inpatient acute care (17%), inpatient substance use treatment (18%), or outpatient primary care (12%) settings. Only 2270 (5%) patients received MAUD across all settings. Female sex and addiction medicine consults positively predicted MAUD prescribing. In contrast, encounters outside inpatient substance use treatment, Hispanic ethnicity, and black or non-white race were negative predictors of MAUD prescribing. Compared to inpatient substance use treatment, inpatient acute care hospitalizations for AUD was associated with a 93% reduced odds of receiving MAUD. CONCLUSIONS: AUD-related ED and inpatient acute care hospital encounters in our healthcare system were common. Nevertheless, prescriptions for MAUD were infrequent in this population, particularly in inpatient settings. Our findings suggest that the initiation of MAUD for patients with alcohol-related diagnoses in acute care settings deserves additional evaluation.

SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

Prospective telehealth analysis of functional performance, frailty, quality of life, and mental health after COVID-19 hospitalization.

BACKGROUND: COVID-19 is a global pandemic with poorly understood long-term consequences. Determining the trajectory of recovery following COVID-19 hospitalization is critical for prioritizing care, allocating resources, facilitating prognosis, and informing rehabilitation. The purpose of this study was to prospectively evaluate recovery following COVID-19 hospitalization. METHODS: Participants age 18 years or older who were hospitalized for ≥24 h due to COVID-19 completed phone/video call virtual assessments (including the 10-time chair rise test) and survey forms at three time points (2-6, 12, and 18 weeks) after hospital discharge. Univariate logistic and linear regression models assessed the associations of the outcomes with primary predictors (categorical age, sex, race/ethnicity group, and categorical pre-hospitalization frailty) at baseline; the same were used to assess differences in change from week 2-6 (continuous outcomes) or outcome persistence/worsening (categorical) at last contact. RESULTS: One hundred nine adults (age 53.0 [standard deviation 13.1]; 53% female) participated including 43 (39%) age 60 or greater; 59% identified as an ethnic and/or racial minority. Over 18 weeks, the mean time to complete the 10-time chair rise test decreased (i.e., improved) by 6.0 s (95% CI: 4.1, 7.9 s; p < 0.001); this change did not differ by pre-hospital frailty, race/ethnicity group, or sex, but those age ≥ 60 had greater improvement. At weeks 2-6, 67% of participants reported a worse Clinical Frailty Scale category compared to their pre-hospitalization level, whereas 42% reported a worse frailty score at 18 weeks. Participants who did not return to pre-hospitalization levels were more likely to be female, younger, and report a pre-hospitalization category of 'very fit' or 'well'. CONCLUSIONS: We found that functional performance improved from weeks 2-6 to 18 weeks of follow-up; that incident clinical frailty developed in some individuals following COVID-19; and that age, sex, race/ethnicity, and pre-hospitalization frailty status may impact recovery from COVID-19. Notably, individuals age 60 and older were more likely than those under age 45 years to return to their pre-hospitalization status and to make greater improvements in functional performance. The results of the present study provide insight into the trajectory of recovery among a representative cohort of individuals hospitalized due to COVID-19.

Worse survival in patients with right ventricular dysfunction and COVID-19-associated acute respiratory distress requiring extracorporeal membrane oxygenation: A multicenter study from the ORACLE Group.

OBJECTIVE: We sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation. METHODS: Six academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared. RESULTS: The cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes. CONCLUSIONS: The presence of right ventricular dysfunction in patients with COVID-19-related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Early ventilator liberation and decreased sedation needs after tracheostomy in patients with COVID-19 infection.

BACKGROUND: Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, published tracheostomy guidelines have generally recommended deferral of the procedure beyond the initial weeks of intubation given high mortality as well as concerns about transmission of the infection to providers. It is unclear whether tracheostomy in patients with COVID-19 infection facilitates ventilator weaning, and long-term outcomes are not yet reported in the literature. METHODS: This is a retrospective study of tracheostomy outcomes in patients with COVID-19 infection at a single-center academic tertiary referral intensive care unit. Patients underwent percutaneous tracheostomy at the bedside; the procedure was performed with limited staffing to reduce risk of disease transmission. RESULTS: Between March 1 and June 30, 2020, a total of 206 patients with COVID-19 infection required mechanical ventilation and 26 underwent tracheostomy at a mean of 25±5 days after initial intubation. Overall, 81% of tracheostomy patients were liberated from the ventilator at a mean of 9±6 days postprocedure, and 54% were decannulated prior to hospital discharge at a mean of 21±10 days postprocedure. Sedation and pain medication requirements decreased significantly in the week after the procedure. In-hospital mortality was 15%. Among tracheostomy survivors, 68% were discharged to a facility. DISCUSSION: The management of patients with COVID-19 related respiratory failure can be challenging due to prolonged ventilator dependency. In our initial experience, outcomes post-tracheostomy in this population are encouraging, with short time to liberation from the ventilator, a high rate of decannulation prior to hospital discharge, and similar mortality to tracheostomy performed for other indications. Barriers to weaning ventilation in this cohort may be high sedation needs and ventilator dyssynchrony. LEVEL OF EVIDENCE: Level V-Therapeutic/care management.