525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial

Abstract Background Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI). Results Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL 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 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). Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red). Table 1. Baseline characteristics Conclusion Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels. Disclosures Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene (Individual(s) Involved: Self): Scientific Research Study Investigator

Conclusion. Mortality rate in outpatients with severe COVID-19 treated with RDV was similar to that reported in inpatients. In this cohort of patients with severe COVID, a majority (84.1%) avoided hospitalization while still receiving appropriate treatment. Results suggest RDV can be safely delivered to outpatients with severe COVID-19.
Methods. Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI).
Results. Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log 10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL 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 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).

Conclusion.
Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels.
Disclosures Background. Monoclonal Antibody Therapy (MAbs) has been shown to reduce rates of ED visits and hospitalizations in patients at risk for severe Covid-19 infection in clinical trials. Since November, three Mabs received emergency use authorization: Bamlanivimab (Bam), Bamlanivimab/Etesevimab (Bam/Ete) and Casirivimab/ Imdevimab (Casi/imdevi). We describe here the real-world effectiveness of implementing early MAb therapy in the outpatient setting for individuals with Covid-19 at high risk of progression.
Methods. We examined the records of 808 UCLA Health patients with a confirmed positive SARS-CoV2 PCR test who were either referred for outpatient Mab therapy or received Mab treatment in the emergency department (ED) between December 10, 2020, and May 3, 2021. The primary outcome of our analysis was the combined 30-day incidence of emergency department visits, hospitalizations, or death following the date of referral. SARS-CoV2 isolates of hospitalized patients who had received Mabs were sequenced to determine the presence of variants.

Figure 1. Covid-19 MAB Treatment Failure Lineages
Conclusion. Our data show that in a real-world setting, combination monoclonal 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. Background. Remdesivir (RDV) was approved by FDA in October 2020 for use in hospitalized patients with COVID-19. We examined the association between RDV treatment and ICU admission in patients hospitalized with COVID-19 pneumonia requiring supplemental oxygen (but not advanced respiratory support) in MN.

Lower Risk of ICU Admission with Remdesivir in Patients Hospitalized with COVID-19 Pneumonia
Methods. COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) is population-based surveillance of hospitalized laboratory confirmed cases of COVID-19. We analyzed COVID-NET cases ≥18 years hospitalized between Mar 23, 2020 and Jan 23, 2021 in MN for which medical record reviews were complete. On admission, included cases had evidence of COVID-19 pneumonia on chest imaging with oxygen saturation < 94% on room air or requiring supplemental oxygen. Cases were excluded if treated with RDV after ICU admission. Multivariable logistic regression was performed to assess the association between RDV treatment and ICU admission.
Conclusion. We found RDV treatment associated with a significantly lower risk of ICU admission in patients admitted to hospital requiring supplemental oxygen, suggesting that treatment may prevent disease progression in this group. Further studies should assess the potential benefit of RDV combination treatment with dexamethasone.
Disclosures. Ruth Lynfield, MD, Nothing to disclose