Eosinophil Recovery in Hospitalized COVID-19 Patients is Associated with Lower Rates of ICU Admission and In-Hospital Mortality: An Observational Cohort Analysis

Background Admission eosinopenia (<100 cells/μL) is associated with poor clinical outcomes in hospitalized COVID-19 patients. However, the effects of eosinophil recovery (defined as reaching ≥50 eosinophils/μL) during hospitalization on COVID-19 outcomes have been inconsistent. Methods The study included 1,831 patients admitted to UCLA hospitals between February 2020 and February 2021 with PCR-confirmed COVID-19. Using competing risk regression and modeling eosinophil recovery as a time-dependent covariate, we evaluated the longitudinal relationship between eosinophil recovery and in-hospital outcomes including ICU admission, need for mechanical ventilation, and in-hospital mortality. All analyses were adjusted for covariates including age, BMI, tobacco smoke exposure, comorbidities known to be risk factors for COVID-19 mortality, and treatments including dexamethasone and remdesivir. Results Eosinophil recovery was evaluated in patients with <50 eosinophils/μL on admission (n=1282). These patients cumulatively amassed 11,633 hospital patient-days;3,985 of those days qualified as eosinophil recovery events, which were represented by 781 patients achieving at least one instance of eosinophil recovery during hospitalization. Despite no significant difference in the rate of mechanical ventilation, eosinophil recoverers had significantly lower rates of in-hospital mortality (aHR: 0.44 [0.29, 0.65], P=0.001) and ICU admission (aHR: 0.25 [0.11, 0.61], P=0.002). Conclusion Trending eosinophil counts during hospitalization is simple and can be performed in resource-limited healthcare settings to track the inflammatory status of a patient. Lack of eosinophil recovery events can identify those at risk for future progression to severe COVID.

Chronic Obstructive Pulmonary Disease is Not Associated with In-Hospital Mortality in COVID-19: An Observational Cohort Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is associated with worsened outcomes in COVID-19 (coronavirus disease 2019). However, data remain fraught with heterogeneity and bias from comorbid conditions. Additionally, data on the impact of COPD-specific factors, such as pre-hospital medications and pulmonologist involvement, remain sparse. Objective: We report a single-center analysis of COPD patients hospitalized with COVID-19 compared to those without COPD. Primary outcomes include ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We evaluated all patients ≥40 years admitted with PCR-confirmed COVID-19 between February 2020 and February 2021. COPD was defined by documented ICD-10 diagnosis of COPD, confirmed smoking history, and active bronchodilator use. We compared outcomes between COPD patients and the remainder of the COVID-19 cohort. Multivariable analyses were adjusted for age, sex, smoking status, and comorbid conditions. Results: Of 1537 hospitalized COVID-19 patients, 122 (7.9%) carried a diagnosis of COPD. The COPD cohort was older (74 ± 13 vs 66 ± 15 years, P < 0.001) and more often former smokers (P < 0.001). Comorbid conditions including diabetes, cardiovascular disease, and kidney disease were more prevalent in the COPD group (P < 0.001). After adjusting for comorbid conditions, the COPD cohort had higher severity scores and trended towards fewer hospital-free days. Among patients with COPD, pre-hospital use of aspirin was associated with decreased ICU admissions (aHR 0.56, P = 0.049) and mechanical ventilation (aHR 0.25, P = 0.008), while LAMAs (long-acting muscarinic antagonists) were associated with decreased in-hospital mortality (aHR 0.34, P = 0.047). Involvement of pulmonology in pre-hospital management of COPD was not found to significantly affect outcomes. Conclusion: When corrected for comorbid illnesses, COPD was associated with more severe disease but not with increased ICU admission, mechanical ventilation, or in-hospital mortality rates. Among COPD patients, prehospital treatment with aspirin and COPD-directed therapies were associated with improved outcomes.

Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis.

BACKGROUND: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users. METHODS: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient's social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users. RESULTS: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 µg/L vs 622 µg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users. CONCLUSIONS: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.

Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).

Rapid deployment of a community engagement study and educational trial via social media: implementation of the UC-COVID study.

BACKGROUND: In response to the COVID-19 pandemic and associated adoption of scarce resource allocation (SRA) policies, we sought to rapidly deploy a novel survey to ascertain community values and preferences for SRA and to test the utility of a brief intervention to improve knowledge of and values alignment with a new SRA policy. Given social distancing and precipitous evolution of the pandemic, Internet-enabled recruitment was deemed the best method to engage a community-based sample. We quantify the efficiency and acceptability of this Internet-based recruitment for engaging a trial cohort and describe the approach used for implementing a health-related trial entirely online using off-the-shelf tools. METHODS: We recruited 1971 adult participants (≥ 18 years) via engagement with community partners and organizations and outreach through direct and social media messaging. We quantified response rate and participant characteristics of our sample, examine sample representativeness, and evaluate potential non-response bias. RESULTS: Recruitment was similarly derived from direct referral from partner organizations and broader social media based outreach, with extremely low study entry from organic (non-invited) search activity. Of social media platforms, Facebook was the highest yield recruitment source. Bot activity was present but minimal and identifiable through meta-data and engagement behavior. Recruited participants differed from broader populations in terms of sex, ethnicity, and education, but had similar prevalence of chronic conditions. Retention was satisfactory, with entrance into the first follow-up survey for 61% of those invited. CONCLUSIONS: We demonstrate that rapid recruitment into a longitudinal intervention trial via social media is feasible, efficient, and acceptable. Recruitment in conjunction with community partners representing target populations, and with outreach across multiple platforms, is recommended to optimize sample size and diversity. Trial implementation, engagement tracking, and retention are feasible with off-the-shelf tools using preexisting platforms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04373135 . Registered on May 4, 2020.

Rapid Deployment of A Community Engagement Study And Educational Trial Via Social Media: Implementation of The UC-COVID Study.

Background: In response to the COVID-19 pandemic and associated adoption of scarce resource allocation (SRA) policies, we sought to rapidly deploy a novel survey to ascertain community values and preferences for SRA, and to test the utility of a brief intervention to improve knowledge of and values alignment with a new SRA policy. Given social distancing and precipitous evolution of the pandemic, Internet enabled recruitment was deemed the best method to engage a community-based sample. We quantify the efficiency and acceptability of this Internet-based recruitment for engaging a trial cohort and describe the approach used for implementing a health-related trial entirely online using off-the-shelf tools. Methods: We recruited 1,971 adult participants (≥18 years) via engagement with community partners and organizations and outreach through direct and social media messaging. We quantified response rate and participant characteristics of our sample, examine sample representativeness, and evaluate potential non-response bias. Results: Recruitment was similarly derived from direct referral from partner organizations and broader social media based outreach, with extremely low study entry from organic (non-invited) search activity. Of social media platforms, Facebook was the highest yield recruitment source. Bot activity was present but minimal and identifiable through meta-data and engagement behavior. Recruited participants differed from broader populations in terms of sex, ethnicity, and education, but had similar prevalence of chronic conditions. Retention was satisfactory, with entrance into the first follow-up survey for 61% of those invited. Conclusions: We demonstrate that rapid recruitment into a longitudinal intervention trial via social media is feasible, efficient, and acceptable. Recruitment in conjunction with community partners representing target populations, and with outreach across multiple platforms, is recommended to optimize sample size and diversity. Trial implementation, engagement tracking, engagement and retention are feasible with off-the-shelf tools using preexisting platforms. Trial Registration: ClinicalTrials.gov registration NCT04373135.

Obesity and smoking as risk factors for invasive mechanical ventilation in COVID-19: A retrospective, observational cohort study.

PURPOSE: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). MATERIALS AND METHODS: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. RESULTS: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. CONCLUSIONS: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.