Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Monoclonal antibodies (mAbs) are the treatment of choice for high-risk ambulatory persons with mild to moderate COVID-19. We studied viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial. Viral load by qPCR and viral culture were performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAb resulted in rapid clearance of culturable virus in participants without treatment-emergent resistance. One day after treatment, 0 of 28 (0%) participants receiving mAb and 16 of 39 (41%) receiving placebo still had culturable virus (p <0.0001); nasal viral loads were only modestly lower in the mAb-treated group at days 2 and 3. Recrudescence of culturable virus was detected in three participants with emerging mAb resistance and viral load rebound. The rapid reduction in shedding of viable SARS-CoV-2 after mAb treatment highlights the potential role of mAbs in preventing disease transmission.

Implementation and Accuracy of BinaxNOW Rapid Antigen COVID-19 Test in Asymptomatic and Symptomatic Populations in a High-Volume Self-Referred Testing Site

The BinaxNOW rapid antigen COVID-19 test had a sensitivity of 87% in symptomatic and 71% asymptomatic individuals when performed by health care workers in a high-throughput setting. The performance may expedite isolation decisions or referrals for time-sensitive monoclonal antibody treatment in communities where timely COVID PCR tests are unavailable.

558. Implementation and Outcomes of a COVID-19 Monoclonal Antibody Treatment Program in an Urban Safety-net Community Hospital

Background Neutralizing monoclonal antibodies (mAbs) bind to the receptor binding domain of the spike protein of SARS-CoV-2. In November 2020, several mAbs were issued an EUA by the FDA as single-dose intravenous (IV) infusions for treatment of mild to moderate COVID-19. mABs were allocated to local health facilities capable of administering infusions and managing side effects. Creating an outpatient infusion program during the COVID-19 winter surge can be logistically difficult. Our goal was to implement a mAb outpatient infusion program at an urban safety-net community hospital designed to serve communities most heavily impacted by COVID-19. Methods The emergency department (ED) fast-track was repurposed for the mAb program with protocols from the infectious diseases physician and antimicrobial stewardship. Education materials with indications for mAbs were distributed in surrounding clinics serving our community. The program was available to all patients meeting criteria outlined in the protocol, 24/7, including but not limited to current ED patients and referrals from facilities in the vicinity. Results Between December 1, 2020 and March 1, 2021, a total of 37 patients were treated: 51% male, 57% Hispanic or Latinx, 27% Black, and 95% (35) represented ZIP codes with high COVID-19 burden (Figure 1). Bamlanivimab was used for each instance and all infusions met criteria. Patient indications for mAb infusion are listed in Figure 2. Parenteral antibiotics were given to 10.8% and 35% received oral antibiotics upon discharge. At 30 days post-infusion, 8% (3) required hospitalization and there were no deaths. Zip codes with high COVID-19 disease burden served by our mAB infusion program Distribution of patients who received mAB infusions by indication Conclusion A mAb outpatient infusion program was successfully deployed in a safety-net community hospital. We believe strengths of the program included the flexible infusion hours and convenient referral site for patients and providers. Of importance, this program was able to provide services to minorities from ZIP codes most heavily impacted by COVID-19. Unfortunately, antibacterial use was common and may reflect broader unnecessary use in COVID-19 patients. Whilst mAb treatment was deemed appropriate in all instances via protocol inclusion criteria, antibacterial stewardship programs may need to expand to ED settings for COVID-19 management. Disclosures All Authors: No reported disclosures

953. Online Medical Education Improves Knowledge of Monoclonal Antibody Treatment for COVID-19 Among Physicians

Background Treatments aimed at patients with mild to moderate COVID-19 offer an opportunity to improve rates of hospitalizations and progression to severe disease. The aim of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of primary care (PCP), infectious disease (ID), and ER/critical care physicians regarding the management of COVID-19 with monoclonal antibody (mAb) therapy. Methods The educational series consisted of 9 online, CME activities in multiple formats. At the individual activity level, educational effect was assessed with a repeated pairs pre-/post-assessment study including a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question, with each participant serving as his/her own control. To assess changes in knowledge, competence, and confidence data from all clinicians who completed both pre- and post-questions were aggregated across activities and stratified by learning themes. McNemar’s test (P&lt; .05) assessed educational effect. Data were collected from 12/20 to 5/21. Results To date, the 9 activities have reached over 24,000 physicians. Selected improvements in knowledge and competence measured as relative % change in correct responses pre/post education across the learning themes are reported here. (i) 45% improvement in PCPs and a 31% improvement in ID specialists’ knowledge/competence in identifying patients who would benefit from mAbs (P &lt; .01). (ii) 83% improvement in PCPs and a 42% improvement in ID specialists’ confidence in identifying patients who would benefit from mAbs (P &lt; .001). (iii) 15% improvement in ID specialists’ knowledge/competence on the clinical data on mAbs for COVID-19 (P &lt; .001). (iv) 32% improvement in PCPs knowledge/competence in understanding the mechanism of action (MOA) of mAbs for COVID-19 (P &lt; .001) Conclusion This series of online, CME-certified educational activities delivered in multiple formats resulted in significant improvements in knowledge and competence regarding the management of patients with mild to moderate COVID-19. This analysis also uncovered remaining educational gaps; 55% of content related to identifying patients who would benefit from mAbs was not retained post-education. Disclosures All Authors: No reported disclosures

Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice

The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical. This study is aimed at determining whether anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week. On postnatal days 2, 4, and 6, the mice were injected intraperitoneally with PBS alone or with anti-Tn monoclonal antibodies at 25 μg/g body weight in 50 μL phosphate-buffered saline (PBS). The mice were divided into four study groups: RA + PBS, RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The kidneys were excised for histology, oxidative stress, cytokine, and Western blot analyses on postnatal day 7. The O2 + PBS mice exhibited significantly higher kidney injury scores, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and nuclear factor-κB (NF-κB) expression, and cytokine levels than did the RA + PBS mice or RA + anti-Tn mice. Anti-Tn monoclonal antibody treatment reduced kidney injury and cytokine levels to normoxic levels. The attenuation of kidney injury was accompanied by a reduction of oxidative stress and NF-κB expression. Therefore, we propose that anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice.