Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Status Asthmaticus Gravidus: Emergency and Critical Care Management of Acute Severe Asthma During Pregnancy.

One-third of women with asthma have deterioration of their asthma during pregnancy, and one-fourth of pregnant women with asthma will experience severe exacerbations necessitating emergency department (ED) visits or hospitalizations. Early recognition of acute severe asthma, including life-threatening status asthmaticus, and aggressive medical interventions with ß2-agonists, anticholinergic agents, and systemic corticosteroids are necessary to treat maternal airway bronchoconstriction, support maternal and fetal oxygenation, and avoid adverse fetal outcomes. This review describes management of acute severe asthma in pregnancy, including status asthmaticus, in the ED and intensive care unit.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

Masking for COVID-19 Is Associated with Decreased Emergency Department Utilization for Non-COVID Viral Illnesses and Respiratory Conditions in Maryland.

BACKGROUND: Masking, which is known to decrease the transmission of respiratory viruses, was not widely practiced in the United States until the coronavirus disease 2019 (COVID-19) pandemic. This provides a natural experiment to determine whether the percentage of community masking was associated with decreases in emergency department (ED) visits due to non-COVID viral illnesses (NCVIs) and related respiratory conditions. METHODS: In this observational study of ED encounters in a 11-hospital system in Maryland during 2019-2020, year-on-year ratios for all complaints were calculated to account for "lockdowns" and the global drop in ED visits due to the pandemic. Encounters for specific complaints were identified using the International Classification of Diseases, version 10. Encounters with a positive COVID test were excluded. Linear regression was used to determine the association of publicly available masking data with ED visits for NCVI and exacerbations of asthma and chronic obstructive pulmonary disease (COPD), after adjusting for patient age, sex, and medical history. RESULTS: There were 285,967 and 252,598 ED visits across the hospital system in 2019 and 2020, respectively. There was a trend toward an association between the year-on-year ratio for all ED visits and the Maryland stay-at-home order (parameter estimate = -0.0804, P = .10). A 10% percent increase in the prevalence of community masking was associated with a 17.0%, 8.8%, and 9.4% decrease in ED visits for NCVI and exacerbations of asthma exacerbations and chronic obstructive pulmonary disease, respectively (P < .001 for all). CONCLUSIONS: Increasing the prevalence of masking is associated with a decrease in ED visits for viral illnesses and exacerbations of asthma and COPD. These findings may be valuable for future public health responses, particularly in future pandemics with respiratory transmission or in severe influenza seasons.