Time to Extubation among ARDS Subjects with and without COVID-19 Pneumonia.

BACKGROUND: Pneumonia from COVID-19 that results in ARDS may require invasive mechanical ventilation. This retrospective study assessed the characteristics and outcomes of subjects with COVID-19-associated ARDS versus ARDS (non-COVID) during the first 6 months of the COVID-19 pandemic in 2020. The primary objective was to determine whether mechanical ventilation duration differed between these cohorts and identify other potential contributory factors. METHODS: We retrospectively identified 73 subjects admitted between March 1 and August 12, 2020, with either COVID-19-associated ARDS (37) or ARDS (36) who were managed with the lung protective ventilator protocol and required > 48 h of mechanical ventilation. Exclusion criteria were the following: <18 years old or the patient required tracheostomy or interfacility transfer. Demographic and baseline clinical data were collected at ARDS onset (ARDS day 0), with subsequent data collected on ARDS days 1-3, 5, 7, 10, 14, and 21. Comparisons were made by using the Wilcoxon rank-sum test (continuous variables) and chi-square test (categorical variables) stratified by COVID-19 status. A Cox proportional hazards model assessed the cause-specific hazard ratio for extubation. RESULTS: The median (interquartile range) mechanical ventilation duration among the subjects who survived to extubation was longer in those with COVID-19-ARDS versus the subjects with non-COVID ARDS: 10 (6-20) d versus 4 (2-8) d; P < .001. Hospital mortality was not different between the two groups (22% vs 39%; P = .11). The competing risks Cox proportional hazard analysis (fit among the total sample, including non-survivors) revealed that improved compliance of the respiratory system and oxygenation were associated with the probability of extubation. Oxygenation improved at a lower rate in the subjects with COVID-19-associated ARDS than in the subjects with non-COVID ARDS. CONCLUSIONS: Mechanical ventilation duration was longer in subjects with COVID-19-associated ARDS compared with the subjects with non-COVID ARDS, which may be explained by a lower rate of improvement in oxygenation status.

A combined assay for quantifying remdesivir and its metabolite, along with dexamethasone, in serum.

BACKGROUND: As global confirmed cases and deaths from coronavirus disease 2019 (COVID-19) surpass 100 and 2.2 million, respectively, quantifying the effects of the widespread treatment of remdesivir (GS-5734, Veklury) and the steroid dexamethasone is becoming increasingly important. Limited pharmacokinetic studies indicate that remdesivir concentrations in serum decrease quickly after dosing, so its primary serum metabolite GS-441524 may have more analytical utility. OBJECTIVES: We developed and validated a method to quantify remdesivir, its metabolite GS-441524 and dexamethasone in human serum. METHODS: We used LC-MS/MS and applied the method to 23 serum samples from seven patients with severe COVID-19. RESULTS: The method has limits of detection of 0.0375 ng/mL for remdesivir, 0.375 ng/mL for GS-441524 and 3.75 ng/mL for dexamethasone. We found low intra-patient variability, but significant inter-patient variability, in remdesivir, GS-441524 and dexamethasone levels. CONCLUSIONS: The significant inter-patient variability highlights the importance of therapeutic drug monitoring of COVID-19 patients and possible dose adjustment to achieve efficacy.