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Conclusion. A COVID-19 IVDM developed using multiscale MOV virology data Conclusion. Mortality rate in outpatients with severe COVID-19 treated with supports drug action on viral infectivity and importance of interplay of treatment and RDV was similar to that reported in inpatients. In this cohort of patients with severe immune response and can describe infection time course and drug effect. IVDM pro - COVID, a majority (84.1%) avoided hospitalization while still receiving appropriate vided mechanistic interpretations for VL drug effect in clinical studies. treatment. Results suggest RDV can be safely delivered to outpatients with severe Disclosures. Youfang Cao, PhD, Merck & Co. (Employee) Wei Gao, PhD, Merck COVID-19. & Co., Inc. (Employee, Shareholder) Ruthie Birger, PhD, Merck (Employee) Julie Disclosures. All Authors: No reported disclosures Stone, PhD, Merck & Co., Inc. (Employee, Shareholder) 524. Assessing the Safety of an Outpatient Remdesivir Infusion Program for Patients with Severe COVID-19 in the Setting of a Pandemic Surge 525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial 1 1 1 1 1 1 Benjamin Gee, BA/BS ; Anita Cheruvanky, MD ; Graciela Faiad, MD ; Mamta K. Jain, MD, MPH ; Mamta K. Jain, MD, MPH ; Hesham Sadek, MD, PhD ; 1 2 1 1 1 1 1 Aldon Li, MD ; Huan Pham, MD ; Earl Quijada, MD ; Susan Sun, MD ; James de Lemos, MD ; Darren mcGuire, MD ; Colby Ayers, MS ; 1 1 2 1 1 1 1 Adam Baghban, MD ; Kaiser Permanente, Riverside, California; Kaiser Permanente Jennifer L. Eiston, PhD ; Claudia Lucas, MS ; Dena Kamel, BA ; Xilong Li, PhD ; 1 1 1 1 Riverside, Riverside, California Barbine Agbor Agbor, MBBS ; Noelle Williams, PhD ; John Schoggins, PhD ; UT Southwestern Medical Center, Dallas, TX Session: P-24. COVID-19 Treatment Background. (i) Remdesivir (RDV) shortens recovery time among COVID-19 Session: P-24. COVID-19 Treatment patients in an inpatient setting. (ii) Treatments for outpatients diagnosed with COVID-19 are limited. (iii) In early 2021, there was a national surge in COVID-19 hospitalizations, Background. Our group performed an in-silico screen to identify FDA approved which resulted in hospital bed and staff shortages. (iv) In the face of this pandemic surge, we drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral rep- piloted a program to expand our RDV treatment capacity by establishing an off-label, out - lication assays, and in vivo pharmacokinetic studies in mice. These studies identified patient infusion tent (OIT) for patients with severe COVID-19. (v) This is a retrospective, atovaquone as a promising candidate for inhibiting viral replication. descriptive report examining the safety and efficacy of this program, with outcomes of Methods. Enrolled patients were randomized in a 2:1 fashion to atovaquone interest being 30-day mortality and hospital admission within the subsequent 30 days 1500 mg twice daily versus matched placebo. Patients received standard of care treat- Methods. (i) The OIT, consisting of 11 chairs capable of treating 35 patients per day, ment including remdesivir, dexamethasone, or convalescent plasma as deemed neces- was operational from January 1 to February 19, 2021. (ii) Patients were referred to the out- sary by the treating team. Patients agreed to allow collection of saliva at baseline and patient RDV program primarily from urgent care (UC) and the emergency department twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted (ED), and from the inpatient setting to complete therapy. Patients received at least one for viral load (VL) measurement by Real-time PCR. Our primary outcome was to dose prior to referral. (iii) Eligibility criteria included a confirmed COVID-19 diagnosis, examine the between group differences in log transformed VL(copies/mL) using gen - radiographic evidence of viral pneumonia, and an oxygen saturation less than or equal to eralized linear mixed-effect models of repeated measures from all samples. Additional 94 on room air. (iv) Exclusion criteria included pregnancy, sepsis, end-stage renal disease analysis of Atovquone plasma concentrations were examined and correlated with viral or GFR < 30, hepatitis with transaminases 10 times the limit of normal. Patients with BMI load and body mass index (BMI). > 40, age > 75, chronic lung disease, dementia, were considered on a case by case basis. (v) Results. Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Patients received dexamethasone and deep vein thrombosis prophylaxis Overall the population was predominately male Hispanic with a mean age of 51 years. Results. (i) A total of 88 patients received 258 infusions. e Th average number of e t Th wo groups were balanced (Table 1) with regard to age, gender, race, co-mor - outpatient infusions per participant was 2.9. (ii) Four out of 88 patients died (4.5%) bidities, days from onset of symptoms, baseline oxygen requirements, and receipt of within 30 days of first dose in the infusion tent. No deaths occurred in the outpatient COVID-19 specific standard of care treatment. A higher proportion with diabetes was setting. (iii) Fourteen out of 88 patients were admitted to the hospital within the sub- noted in the Atovaquone arm. The log VL was 5.25 copies/mL vs. 4.79 copies/mL at sequent 30 days (15.9%). (iv) 11/14 admissions (78.6%) were due to progression of baseline in the atovaquone vs. placebo group. Although there was a decrease in VL COVID-19. There were no admissions due to adverse drug reactions over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma Table 1. Patient Characteristics concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005). Table 2. Admissions Within Subsequent 30 Days Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red). Abstracts • OFID 2021:8 (Suppl 1) • S363 Table 1. Baseline characteristics (HR 3.24, 95% CI 1.02-10.26) as well as high social vulnerability index (HR 1.87, 95% CI 1.13-3.10). Over one-third of hospitalized patients who had received Mabs were confirmed to have the California variant (B.1.427/29) (Figure 1). Figure 1. Covid-19 MAB Treatment Failure Lineages Conclusion. Our data show that in a real-world setting, combination mono- clonal antibody therapy, not monotherapy, significantly reduced ED visits and hospital admissions, likely due to the presence of the California variants. High socioeconomic vulnerability and certain medical conditions increased risk of treatment failure. Disclosures. Omai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator) 527. Lower Risk of ICU Admission with Remdesivir in Patients Hospitalized with COVID-19 Pneumonia 1 2 3 Sarah Lim, MBBCh ; Pamela Schreiner, PhD ; Alan Lifson, MD, MPH ; 4 4 4 Erica Bye, MPH ; Kathryn Como-Sabetti, MPH ; Ruth Lynfield , MD ; 4 1 2 Ruth Lynfield , MD ; MN Department of Health, St Paul, Minnesota; University Conclusion. Although atovaquone showed promising in vitro antiviral properties of Minnesota School of Public Health, Minneapolis, Minnesota; University of for COVID-19, in this pilot study we did not detect a change in VL in patients who Minnesota, Minneapolis, Minnesota; Minnesota Department of Health, St. Paul, received atovaquone compared to placebo, possibly due to failure of patients achieve Minnesota adequate drug levels. Session: P-24. COVID-19 Treatment Disclosures. Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; Background. Remdesivir (RDV) was approved by FDA in October 2020 for GlaxoSmithKline (Individual(s) Involved: Self ): Scientific Research Study Investigator; use in hospitalized patients with COVID-19. We examined the association be- Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene tween RDV treatment and ICU admission in patients hospitalized with COVID-19 (Individual(s) Involved: Self ): Scientific Research Study Investigator pneumonia requiring supplemental oxygen (but not advanced respiratory support) in MN. Methods. COVID-19-Associated Hospitalization Surveillance Network 526. Implementation of Use of Monoclonal Antibody Therapy in a Large (COVID-NET) is population-based surveillance of hospitalized laboratory confirmed Academic Center for the Outpatient Treatment of Covid-19: Impact on 30 Day cases of COVID-19. We analyzed COVID-NET cases ≥18 years hospitalized between Hospitalization Rates, ED Visits and Death Mar 23, 2020 and Jan 23, 2021 in MN for which medical record reviews were com- 1 1 1 Azra Bhimani, MD ; Vinay Srinivasan, BA, MPH ; Stacey Weinstein, MD ; plete. On admission, included cases had evidence of COVID-19 pneumonia on chest Nathan Clemons, PhD, MLS ; Quanna Batiste, DNP, MSHCSM, RN, NEA-BC, imaging with oxygen saturation < 94% on room air or requiring supplemental oxygen. 1 1 FABC ; Shangxin Yang, PhD, D(ABMM), MLS(ASCP) ; Omai Garner, PhD, Cases were excluded if treated with RDV aer I ft CU admission. Multivariable logistic 1 2 1 D(ABMM) ; Tara Vijayan, M.D., M.P.H. ; University of California, Los Angeles, Los regression was performed to assess the association between RDV treatment and ICU Angeles, CA; UCLA David Geffen School of Medicine, Los Angeles, CA admission. Results. Complete records were available for 8,666 cases (36% of admissions Session: P-24. COVID-19 Treatment statewide). 1,996 cases were included in the analysis, of which 908 were treated with Background. Monoclonal Antibody Therapy (MAbs) has been shown to reduce RDV. 83% of cases were residents of the 7-county metro area of Minneapolis-St. Paul. rates of ED visits and hospitalizations in patients at risk for severe Covid-19 infec- Mean age was 59.7 years (IQR 48-72), 55% were male, and the mean RDV treatment tion in clinical trials. Since November, three Mabs received emergency use authoriza- duration was 4.8 days (range 2-15). The proportion of cardiovascular disease (30.6% vs tion: Bamlanivimab (Bam), Bamlanivimab/Etesevimab (Bam/Ete) and Casirivimab/ 23.9%, p=.003), renal disease (16.6% vs 7.6%, p< .001), and diabetes (34.7% vs 29.5%, Imdevimab (Casi/imdevi). We describe here the real-world effectiveness of imple - p=0.01) was higher in the RDV untreated group, while obesity (22.3% vs 8.4%, p< menting early MAb therapy in the outpatient setting for individuals with Covid-19 at .001) and dexamethasone use (54.7% vs 15%, p< .001) was more common in the RDV high risk of progression. treated group. RDV untreated patients were more likely to be admitted to an ICU (18% Methods. We examined the records of 808 UCLA Health patients with a con- vs 8.9%, p< .001) and had higher inpatient mortality than those treated with RDV firmed positive SARS-CoV2 PCR test who were either referred for outpatient Mab (11% vs 4.4%, p< .001). Aer ad ft justment for dexamethasone use, age, sex and diabetes, therapy or received Mab treatment in the emergency department (ED) between treatment with RDV was associated with 48% lower odds of ICU admission (OR 0.52, December 10, 2020, and May 3, 2021. The primary outcome of our analysis was the 0.39-0.7, p< .001). combined 30-day incidence of emergency department visits, hospitalizations, or death Conclusion. We found RDV treatment associated with a significantly lower risk following the date of referral. SARS-CoV2 isolates of hospitalized patients who had of ICU admission in patients admitted to hospital requiring supplemental oxygen, sug- received Mabs were sequenced to determine the presence of variants. gesting that treatment may prevent disease progression in this group. Further studies Results. Of 808 patients, 383 were referred for treatment but did not receive treat- should assess the potential benefit of RDV combination treatment with dexamethasone. ment, 109 received Mabs in the ED and 316 patients were treated in an outpatient Disclosures. Ruth Lynfield, MD , Nothing to disclose setting. Composite 30-day mortality, ED visits and hospital admissions were signifi - cantly reduced in the combination therapy group (Bam/Ete or Cas/Imd) compared with monotherapy (Bam alone) or no treatment groups (aHR 0.16, 95% CI .038, .67). 528. Hospital Course of Patients Receiving Bamalanivimab: A Real World Significant factors associated with the composite outcome included: history of lung Analysis 1 1 disease (HR 4.46, 95% CI 2.89-6.90), cardiovascular disease (HR 1.87, 95% CI 1.12- Madeline Belk, PharmD ; Jonathan Edwards, Pharm.D., BCPS-AQ ID, BCGP ; 1 1 3.12), kidney disease (HR 2.04, 95% CI 1.27-3.25), and immunocompromised state Ali Hassoun, M.D. ; Huntsville Hospital, Huntsville, Alabama S364 • OFID 2021:8 (Suppl 1) • Abstracts
Open Forum Infectious Diseases – Oxford University Press
Published: Dec 4, 2021
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