Clinical Course and Outcome of COVID-19 Acute Respiratory Distress Syndrome: Data From a National Repository.

BACKGROUND: Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS). RESEARCH QUESTION: The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse. STUDY DESIGN AND METHODS: Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively. RESULTS: The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m2, diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. CONCLUSIONS: Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial.

OBJECTIVE: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. DESIGN: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. SETTING: Tertiary care children's hospital. PATIENTS: Children (0-18years) with ARDS undergoing mechanical ventilation. INTERVENTIONS: 35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. RESULTS: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. CONCLUSION: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.