Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization.

BACKGROUND: The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death. METHODS: We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient's clinical course to characterize the effect of remdesivir on progression along the 4 pathways above. RESULTS: Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio [HR], 0.73; 95% confidence interval [CI]: .59-.91) and increased clinical improvement (HR, 1.22; 95% CI: 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (HR, 0.74; 95% CI: .57-.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (HR, 0.73; 95% CI: .53-1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline. CONCLUSIONS: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.

Post-COVID-19 Pulmonary Fibrosis: Novel Sequelae of the Current Pandemic.

Since the initial identification of the novel coronavirus SARS-CoV-2 in December 2019, the COVID-19 pandemic has become a leading cause of morbidity and mortality worldwide. As effective vaccines and treatments begin to emerge, it will become increasingly important to identify and proactively manage the long-term respiratory complications of severe disease. The patterns of imaging abnormalities coupled with data from prior coronavirus outbreaks suggest that patients with severe COVID-19 pneumonia are likely at an increased risk of progression to interstitial lung disease (ILD) and chronic pulmonary vascular disease. In this paper, we briefly review the definition, classification, and underlying pathophysiology of interstitial lung disease (ILD). We then review the current literature on the proposed mechanisms of lung injury in severe COVID-19 infection, and outline potential viral- and immune-mediated processes implicated in the development of post-COVID-19 pulmonary fibrosis (PCPF). Finally, we address patient-specific and iatrogenic risk factors that could lead to PCPF and discuss strategies for reducing risk of pulmonary complications/sequelae.