554. Clinical Impact of Monoclonal Antibody Therapy with SARS-CoV-2 Infection

Abstract Background The novel coronavirus SARS-CoV2 is the causative agent for COVID-19 responsible for the ongoing global pandemic. The spike protein on its surface binds to the angiotensin-converting enzyme 2 receptor helps to enter human cells. Neutralizing antibodies to this protein can be protective and helpful in alleviating symptoms. Monoclonal antibodies (mAb) have been utilized in the U.S. under an emergency use authorization by the FDA, including bamlanivimab (BAM) and casirivimab-imdevimab (CAR/IMD). We report our experience of using COVID mAb. Methods We conducted a retrospective chart review of patients that received CAR/IMD or BAM between December 1st, 2020, and May 15th, 2021. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of mAb. Results 463 patients with mild to moderate symptoms of SARS-CoV2 received mAb: 355(176 Men) BAM, 108(53 Men) CAR/IMD. The median BMI was 31 (17.4 to 62.5), 85% Caucasian, 4% Asian, 3% African American, 4% Hispanic, 4% others. The average duration of symptoms was 3.4 days and included cough (74%), malaise (71%), Headache (28%), dyspnea (28%), rhinorrhea (25%), fever (20%), diarrhea (18%), and anosmia (14%). Risk factors included hypertension (65%), diabetes mellitus (32%), coronary artery disease (22%), asthma (16%), COPD (9%), CHF (9%), CKD (8%), active malignancy (6%), and immunocompromised state (7%). Those who received BAM were older (p=0.000) and have underlying dementia and congestive heart failure (p=0.025 and 0.034, respectively). 27 patients (2 CAR/IMG, 25 BAM) got admitted to the hospital due to worsening of their respiratory status and were treated for COVID-19. 4 patients in the BAM group and 0 in the CAR/IMD group died. 2 patients developed a mild allergic reaction to CAR/IMD, no other side effects were reported in both groups. 37 patients (19 CAR/IMD, 18 BAM) received mRNA COVID vaccine prior. Overall mortality rate was 0.8%. There was no significant difference between BAM and CAR/IMR in terms of hospitalization (p= 0.104) or mortality (p=0.268). Conclusion Treatment with BAM versus CAR/IMR was well tolerated and resulted in similar outcomes in terms of hospitalization or mortality. Disclosures All Authors: No reported disclosures

(34.3%) received remdesivir, and 49 (8.8%) received tocilizumab. By the cutoff date for data analysis, 389 (69.6%) patients survived, and 170 (30.4%) had died. The bivariable Cox regression models showed decreased hazard of in-hospital death associated with the administration of steroids (Figure 1), remdesivir (Figure 2), and tocilizumab ( Figure 3). This association persisted in the multivariable Cox regression controlling for other predictors (Figure 4). The E value for the multivariable Cox regression point estimates and the lower confidence intervals are shown in Table 1. The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. The hazard ratios were derived from a multivariable Cox regression model adjusting for age as a continuous variable, qSOFA score, noninvasive positive-pressure ventilation, and invasive mechanical ventilation. Table 1. Sensitivity analysis of unmeasured confounding using E-values CI, confidence interval. Point estimate from multivariable Cox regression model. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully: i.e., a confounder not included in the multivariable Cox regression model associated with remdesivir or tocilizumab use and in-hospital death in patients with severe COVID-19 by a hazard ratio of 1.64-fold or 1.54-fold each, respectively, could explain away the lower confidence limit, but weaker confounding could not.
Conclusion. For patients with severe COVID-19 admitted to our community hospital, the use of steroids, remdesivir, and tocilizumab were significantly associated with a slower progression to in-hospital death while controlling for other predictors included in the models.
Disclosures.   in adults with positive SARS-CoV-2 viral testing and at high risk for progression to severe COVID-19 with up to 10 days of symptoms. This study assessed the impact of MAT on COVID-19-related ER visits, admissions, and mortality for patients diagnosed with COVID-19.
Methods. This was a single-center, retrospective study at The Ohio State University Wexner Medical Center to compare COVID-19-related ER visits, admissions, and mortality at 30 days after receiving MAT in the outpatient setting with either bamlanivimab or casirivimab-imdevimab in adult patients diagnosed with SARS-CoV-2 between November 16, 2020 and February 2, 2021. Outcomes in patients who received MAT were compared to those of a control group of patients diagnosed with COVID-19 in the outpatient setting from May 16, 2020 through November 15, 2020 who would have qualified for MAT through EUA criteria had it been available. Statistical analysis used logistic regression analysis with backward selection to determine the odds ratios (OR) and the 95% confidence interval to evaluate the relationship between patient clinical characteristics and outcomes.
Results. This study cohort included 1,944 patients, including 943 who received MAT and 1,001 in the control group. The MAT group included 658 who received bamlanivimab and 285 who received casirivimab-imdevimab. Patients who received MAT compared to the control group had a lower rate of COVID-19 related ER visits (3.3% vs 7.4%, p = < 0.0001) and hospital admissions (4.0% vs 7.8%, p = < 0.0001). No statistically significant difference was seen in mortality between the MAT group (0.5%) and control group (1.1%, p = 0.17). After accounting for potential confounders, the difference between the monoclonal antibody and control groups remained significant for ER visits and hospital admissions as reflected in the table.

Conclusion.
Patients who received MAT for COVID-19 in the outpatient setting had a lower rate of COVID-19-related 30 day ER visits and hospitalizations compared to those who did not receive MAT, adjusting for potential confounders. Background. The novel coronavirus SARS-CoV2 is the causative agent for COVID-19 responsible for the ongoing global pandemic. The spike protein on its surface binds to the angiotensin-converting enzyme 2 receptor helps to enter human cells. Neutralizing antibodies to this protein can be protective and helpful in alleviating symptoms. Monoclonal antibodies (mAb) have been utilized in the U.S. under an emergency use authorization by the FDA, including bamlanivimab (BAM) and casirivimab-imdevimab (CAR/IMD). We report our experience of using COVID mAb.
Methods. We conducted a retrospective chart review of patients that received CAR/IMD or BAM between December 1st, 2020, and May 15th, 2021. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of mAb.
Conclusion. Treatment with BAM versus CAR/IMR was well tolerated and resulted in similar outcomes in terms of hospitalization or mortality.
Disclosures. All Authors: No reported disclosures Background. As remdesivir (GS-5734) has become a leading treatment for COVID-19, we sought to assess remdesivir utilization patterns, including utilization of concomitant and supportive therapies, and heterogeneity in treatment approaches.

Utilization of Remdesivir for COVID-19 in the National Veterans Affairs
Methods. Our retrospective cohort study included hospitalized Veterans with positive COVID-19 PCR tests treated with remdesivir, from 03/2020 through 4/2021. Using exposure mapping of barcode medication administration records and medication dispensings, we assessed other medications received by each patient on each day of remdesivir treatment. Heterogeneity was defined as patterns of treatment (drug & duration) not shared by any other patient.
Conclusion. Among hospitalized patients with COVID-19 in the national VA Healthcare system receiving remdesivir, remdesivir was initiated early in the admission and substantial heterogeneity was observed in concomitant and supportive therapies during remdesivir treatment.
Disclosures Background. Mexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm.
Methods. An experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days.
Results. The final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p< 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p< 0.001).
Differences for support oxygen at baseline and discharge Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico Conclusion. The use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated.
Disclosures. All Authors: No reported disclosures