Reports From the Field

Successful COVID-19 Surge Management With Monoclonal Antibody Infusion in Emergency Department Patients

Journal of Clinical Outcomes Management. 2022 January;29(1):32-38 | doi:10.12788/jcom.0078

Author(s):

Daniel S. Chow, MD

Ruchi Desai, BS

Mazaya Soundara, BS

Shruti Gohil, MD, MPH

Peter D. Chang, MD

Alpesh Amin, MD, MBA

PDF Download

References

1. Global map. Johns Hopkins University & Medicine Coronavirus Resource Center. Updated November 9, 2021. Accessed November 9, 2021. https://coronavirus.jhu.edu/map.html

2. Truog RD, Mitchell C, Daley GQ. The toughest triage — allocating ventilators in a pandemic. N Engl J Med. 2020;382(21):1973-1975. doi:10.1056/NEJMp2005689

3. Cavallo JJ, Donoho DA, Forman HP. Hospital capacity and operations in the coronavirus disease 2019 (COVID-19) pandemic—planning for the Nth patient. JAMA Health Forum. 2020;1(3):e200345. doi:10.1001/jamahealthforum.2020.0345

4. Eriksson CO, Stoner RC, Eden KB, et al. The association between hospital capacity strain and inpatient outcomes in highly developed countries: a systematic review. J Gen Intern Med. 2017;32(6):686-696. doi:10.1007/s11606-016-3936-3

5. Bravata DM, Perkins AJ, Myers LJ, et al. Association of intensive care unit patient load and demand with mortality rates in US Department of Veterans Affairs hospitals during the COVID-19 pandemic. JAMA Netw Open. 2021;4(1):e2034266. doi:10.1001/jamanetworkopen.2020.34266

6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 - final report. N Engl J Med. 2020;383(19);1813-1826. doi:10.1056/NEJMoa2007764

7. Coronavirus (COVID-19) update: FDA authorizes monoclonal antibody for treatment of COVID-19. US Food & Drug Administration. November 9, 2020. Accessed November 9, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19

8. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med. 2021;384(3):229-237. doi:10.1056/NEJMoa2029849

9. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002

10. Chen X, Li R, Pan Z, et al. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. Cell Mol Immunol. 2020;17(6):647-649. doi:10.1038/s41423-020-0426-7

11. Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2021;325(7):632-644. doi:10.1001/jama.2021.0202

12. Toy S, Walker J, Evans M. Highly touted monoclonal antibody therapies sit unused in hospitals The Wall Street Journal. December 27, 2020. Accessed November 9, 2021. https://www.wsj.com/articles/highly-touted-monoclonal-antibody-therapies-sit-unused-in-hospitals-11609087364

13. Anti-SARS-CoV-2 monoclonal antibodies. NIH COVID-19 Treatment Guidelines. Updated October 19, 2021. Accessed November 9, 2021. https://www.covid19treatmentguidelines.nih.gov/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/

14. Langellier BA. Policy recommendations to address high risk of COVID-19 among immigrants. Am J Public Health. 2020;110(8):1137-1139. doi:10.2105/AJPH.2020.305792

15. Verderese J P, Stepanova M, Lam B, et al. Neutralizing monoclonal antibody treatment reduces hospitalization for mild and moderate COVID-19: a real-world experience. Clin Infect Dis. 2021;ciab579. doi:10.1093/cid/ciab579

16. Levine DM, Linder JA, Landon BE. Characteristics of Americans with primary care and changes over time, 2002-2015. JAMA Intern Med. 2020;180(3):463-466. doi:10.1001/jamainternmed.2019.6282

17. Rust G, Ye J, Daniels E, et al. Practical barriers to timely primary care access: impact on adult use of emergency department services. Arch Intern Med. 2008;168(15):1705-1710. doi:10.1001/archinte.168.15.1705

18. COVID-19 Hospitalization Tracking Project: analysis of HHS data. University of Minnesota. Carlson School of Management. Accessed November 9, 2021. https://carlsonschool.umn.edu/mili-misrc-covid19-tracking-project

19. Zare˛bska-Michaluk D, Jaroszewicz J, Rogalska M, et al. Impact of kidney failure on the severity of COVID-19. J Clin Med. 2021;10(9):2042. doi:10.3390/jcm10092042

20. Shahid Z, Kalayanamitra R, McClafferty B, et al. COVID‐19 and older adults: what we know. J Am Geriatr Soc. 2020;68(5):926-929. doi:10.1111/jgs.16472

21. Coronavirus (COVID-19) update: FDA revokes emergency use authorization for monoclonal antibody bamlanivimab. US Food & Drug Administration. April 16, 2021. Accessed November 9, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab

From the Center for Artificial Intelligence in Diagnostic Medicine, University of California, Irvine, CA (Drs. Chow and Chang, Mazaya Soundara), University of California Irvine School of Medicine, Irvine, CA (Ruchi Desai), Division of Infectious Diseases, University of California, Irvine, CA (Dr. Gohil), and the Department of Medicine and Hospital Medicine Program, University of California, Irvine, CA (Dr. Amin).

Background: The COVID-19 pandemic has placed substantial strain on hospital resources and has been responsible for more than 733 000 deaths in the United States. The US Food and Drug Administration has granted emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in the US for patients with early-stage high-risk COVID-19.

Methods: In this retrospective cohort study, we studied the emergency department (ED) during a massive COVID-19 surge in Orange County, California, from December 4, 2020, to January 29, 2021, as a potential setting for efficient mAb delivery by evaluating the impact of bamlanivimab use in high-risk COVID-19 patients. All patients included in this study had positive results on nucleic acid amplification detection from nasopharyngeal or throat swabs, presented with 1 or more mild or moderate symptom, and met EUA criteria for mAb treatment. The primary outcome analyzed among this cohort of ED patients was overall improvement, which included subsequent ED/hospital visits, inpatient hospitalization, and death related to COVID-19.

Results: We identified 1278 ED patients with COVID-19 not treated with bamlanivimab and 73 patients with COVID-19 treated with bamlanivimab during the treatment period. Of these patients, 239 control patients and 63 treatment patients met EUA criteria. Overall, 7.9% (5/63) of patients receiving bamlanivimab had a subsequent ED/hospital visit, hospitalization, or death compared with 19.2% (46/239) in the control group (P = .03).

Conclusion: Targeting ED patients for mAb treatment may be an effective strategy to prevent progression to severe COVID-19 illness and substantially reduce the composite end point of repeat ED visits, hospitalizations, and deaths, especially for individuals of underserved populations who may not have access to ambulatory care.

Keywords: COVID-19; mAb; bamlanivimab; surge management.

Since December 2019, the novel pathogen SARS-CoV-2 has spread rapidly, culminating in a pandemic that has caused more than 4.9 million deaths worldwide and claimed more than 733 000 lives in the United States.¹ The scale of the COVID-19 pandemic has placed an immense strain on hospital resources, including personal protective equipment (PPE), beds, ventilators and personnel.^2,3 A previous analysis demonstrated that hospital capacity strain is associated with increased mortality and worsened health outcomes.⁴ A more recent analysis in light of the COVID-19 pandemic found that strains on critical care capacity were associated with increased COVID-19 intensive care unit (ICU) mortality.⁵ While more studies are needed to understand the association between hospital resources and COVID-19 mortality, efforts to decrease COVID-19 hospitalizations by early targeted treatment of patients in outpatient and emergency department (ED) settings may help to relieve the burden on hospital personnel and resources and decrease subsequent mortality.

Current therapeutic options focus on inpatient management of patients who progress to acute respiratory illness while patients with mild presentations are managed with outpatient monitoring, even those at high risk for progression. At the moment, only remdesivir, a viral RNA-dependent RNA polymerase inhibitor, has been approved by the US Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients.⁶ However, in November 2020, the FDA granted emergency use authorization (EUA) for monoclonal antibodies (mAbs), monotherapy, and combination therapy in a broad range of early-stage, high-risk patients.^7-9 Neutralizing mAbs include bamlanivimab (LY-CoV555), etesevimab (LY-CoV016), sotrovimab (VIR-7831), and casirivimab/imdevimab (REGN-COV2). These anti–spike protein antibodies prevent viral attachment to the human angiotensin-converting enzyme 2 receptor (hACE2) and subsequently prevent viral entry.¹⁰ mAb therapy has been shown to be effective in substantially reducing viral load, hospitalizations, and ED visits.¹¹

Despite these promising results, uptake of mAb therapy has been slow, with more than 600 000 available doses remaining unused as of mid-January 2021, despite very high infection rates across the United States.¹² In addition to the logistical challenges associated with intravenous (IV) therapy in the ambulatory setting, identifying, notifying, and scheduling appointments for ambulatory patients hamper efficient delivery to high-risk patients and limit access to underserved patients without primary care providers. For patients not treated in the ambulatory setting, the ED may serve as an ideal location for early implementation of mAb treatment in high-risk patients with mild to moderate COVID-19.

The University of California, Irvine (UCI) Medical Center is not only the major premium academic medical center in Orange County, California, but also the primary safety net hospital for vulnerable populations in Orange County. During the surge period from December 2020 through January 2021, we were over 100% capacity and had built an onsite mobile hospital to expand the number of beds available. Given the severity of the impact of COVID-19 on our resources, implementing a strategy to reduce hospital admissions, patient death, and subsequent ED visits was imperative. Our goal was to implement a strategy on the front end through the ED to optimize care for patients and reduce the strain on hospital resources.

We sought to study the ED during this massive surge as a potential setting for efficient mAb delivery by evaluating the impact of bamlanivimab use in high risk COVID-19 patients.

Methods

We conducted a retrospective cohort study (approved by UCI institutional review board) of sequential COVID-19 adult patients who were evaluated and discharged from the ED between December 4, 2020, and January 29, 2021, and received bamlanivimab treatment (cases) compared with a nontreatment group (control) of ED patients.

Using the UCI electronic medical record (EMR) system, we identified 1278 ED patients with COVID-19 not treated with bamlanivimab and 73 patients with COVID-19 treated with bamlanivimab during the months of December 2020 and January 2021. All patients included in this study met the EUA criteria for mAb therapy. According to the Centers for Disease Control and Prevention (CDC), during the period of this study, patients met EUA criteria if they had mild to moderate COVID-19, a positive direct SARS-CoV-2 viral testing, and a high risk for progressing to severe COVID-19 or hospitalization.¹³ High risk for progressing to severe COVID-19 and/or hospitalization is defined as meeting at least 1 of the following criteria: a body mass index of 35 or higher, chronic kidney disease (CKD), diabetes, immunosuppressive disease, currently receiving immunosuppressive treatment, aged 65 years or older, aged 55 years or older and have cardiovascular disease or hypertension, or chronic obstructive pulmonary disease (COPD)/other chronic respiratory diseases.¹³ All patients in the ED who met EUA criteria were offered mAb treatment; those who accepted the treatment were included in the treatment group, and those who refused were included in the control group.