Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.