Secondary Logo

Journal Logo

Original Articles

Impact of Rapidly Deployed COVID-19 Monoclonal Antibody Infusion Clinics on Rate of Hospitalization

Delasobera, Bronson E. MD; Saggar, Tara MD; Goodwin, Jennifer N. MBA; Joy, Amanda MS, PA-C; Henry, Kiersten N. DNP, ACNP-BC; Levin, Bonnie PharmD, MBA; Hager, David D. MD; McAlduff, Joel MD; DeSale, Sameer PhD; Owens, Xavier MHSA; Wortmann, Glenn W. MD; Kumar, Princy N. MD

Author Information
Infectious Diseases in Clinical Practice: March 2022 - Volume 30 - Issue 2 - p 1-6
doi: 10.1097/IPC.0000000000001109
  • Open

Abstract

A major focus of the initial treatment of COVID-19 was to limit disease progression in the inpatient setting. However, as the pandemic progressed, the need for outpatient treatment options became apparent. In November 2020, the Food and Drug Administration approved an Emergency Use Authorization (EUA) of 2 monoclonal antibody treatments, bamlanivimab (LY-CoV555; Eli Lilly and Company) and casirivimab/imdevimab (REGN-COV2; Regeneron Pharmaceuticals), for outpatient management of mild to moderate COVID-19. At the time of authorization, these drugs were indicated for nonhospitalized, symptomatic patients within 10 days of first symptom onset, who were at high risk for progression to severe COVID-19 or hospitalization.

Clinical trials have shown that monoclonal antibodies decrease healthcare utilization. In the initial BLAZE-1 interim analysis, rates of hospitalization or emergency department (ED) visits were 1.6% in the bamlanivimab group and 6.3% in the placebo group.1 Similarly, in the initial REGN-COV2 trial, 3% of patients who received casirivimab/imdevimab and 6% of patients who received placebo reported at least 1 medically attended visit.2

Challenges with logistics and operations to implement infusion clinics have resulted in underutilization of this therapeutic modality nationally. Barriers to infusion, recently identified in federal government efforts to increase infusion rates in high-risk patients, include staffing, infusion center capacity, availability of equipment to administer intravenous infusions, and patient and provider education.3,4 Because patients who were most likely to benefit from the monoclonal antibody were still infectious and posed a risk for transmission, a multistep process to provide the monoclonal antibody in a safe, efficient, and timely manner was enacted at our institution. The process included the education of referring providers, development of an integrated network of referrals and communication, and identification of highest-risk patients to create a seamless model for delivering the monoclonal antibody to patients early in their disease process.

This infrastructure proves to be important as the pandemic continues to evolve with changes in the dominant variant, and hence, changes to the monoclonal antibody treatments are recommended. Bamlanivimab alone is no longer available under EUA and instead must be given with etesevimab. However, it is the infrastructure put in place to administer monoclonal antibodies that continues to be the most efficient in providing safe and effective therapy to patients in the outpatient setting. This report highlights the development and execution of a program that delivers the monoclonal antibody to outpatients while overcoming the delivery challenges seen nationwide. It also provides analysis of the effectiveness of bamlanivimab during its use.

OBJECTIVES

This study describes the rapid build-out and operations of 2 hospital-based bamlanivimab infusion clinics, the priority scoring system developed to identify eligible patients, and results of a retrospective cohort analysis of eligible patients who received bamlanivimab compared with those who did not receive monoclonal antibody. The primary end point was hospitalization rate. Secondary end points were ED visits and mortality.

METHODS

Implementation of Centers and Referral Process

An emergency task force was formed to create an accelerated response to delivering monoclonal antibody treatments to outpatients in a large Mid-Atlantic Health system. Critical to treatment was identifying and engaging patients immediately upon presentation of symptoms through providers at primary care, urgent care, and ED locations within the system. In the electronic health record, a prompt (Fig. 1) was created so that provider could identify patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result, followed by screening questions for risk factors that could lead to a severe course of COVID-19.

F1
FIGURE 1:
Provider referral form.

By focusing on patients older than 65 years or with higher body mass indexes (BMIs; >35 kg/m2), a scoring rubric (Fig. 2) was created to ensure that patients with the highest risk factors would be prioritized for treatment with the constrained supply of monoclonal antibody medication. By creating prompts for the primary provider in the outpatient setting, which incorporated a scoring mechanism, an easy tool was developed to identify patients in minutes within busy primary care, urgent care, and ED facilities.

F2
FIGURE 2:
Scoring rubric.

The task force also identified ease of access to the infusion process as a potential obstacle for patients receiving treatment. Infusion sites were created to capture these patients early in their disease. The first 2 locations were outpatient infusion centers created at a DC hospital and a Maryland hospital. These infusion sites were located in existing space repurposed into 4-chair infusion suites with confined waiting rooms for observation postinfusion and restrooms to limit COVID-19 patient contact with other patients in the hospital. The infusion sites were staffed by registered nurses and support staff outfitted in personal protective equipment to provide a safe environment to enable the infusion. Department of Health authorizations and infection prevention standards were obtained and implemented specific to COVID-19. Patients were given a call center number to schedule their appointment within 24 hours of referral. The second stream of infusion sites were the EDs of 3 hospitals. Patients who arrived with COVID-19 symptoms (or mild progression of their known diagnosis) and found to be positive upon arrival and within the 10 days window of treatment were treated on site before discharge. The benefit of both streams of treatment involved the close proximity and collaboration of the hospital pharmacies that partnered with the locations to ensure prompt, safe treatments.

Another critical element to the implementation of the monoclonal antibody treatment program was leveraging the health system's distributed care network of primary, specialty, and urgent care extending out into communities to bring health care closer to patients. This network allowed for accessing patients in remote areas and incorporating them into the monoclonal antibody referral process. System-wide communication led by clinical leaders in infectious disease, emergency medicine, urgent care, and primary care highlighted the importance of this medication in the COVID-19 pandemic and gave healthcare providers within the system the tools and a path for referral and clinical exchange. This matrix allowed for a flow of patients from identification to risk assessment to referral and ultimately to treatment. Collaboration with nonsystem providers allowed referral of high-risk patients external to the health system for monoclonal antibody infusion.

Study Design and Setting

This was a retrospective cohort study using patient data from a large healthcare system in the Mid-Atlantic region and was approved by the institutional review board. All patients referred for monoclonal antibody treatment in this healthcare system were included in the study. Those who received the monoclonal antibody infusion were considered the treatment group, whereas those referred (ie, met the criteria and were given the referral information) but who chose not to receive the monoclonal antibody were considered the control group. These infusions took place in Washington, DC, and Maryland, in designated EDs and hospital outpatient infusion areas designed specifically for monoclonal antibody infusions.

Study Patients

Patients were referred for monoclonal antibody treatment with bamlanivimab following the EUA approval guidelines. Patients had to be 12 years or older with a documented positive COVID-19 test result (either antigen or polymerase chain reaction testing) and have mild to moderate symptoms for less than 10 days. New oxygen supplementation or an increase in baseline oxygen supplementation was considered the exclusion criteria. Given limited monoclonal antibody supplies, a scoring system was developed to prioritize those patients with more comorbidities or with an increased risk of hospitalization with COVID-19 infection. In the first few weeks of treatment, the scoring threshold was higher (those with a score of 3 or higher were eligible and referred). Over time, as supply increased, the scoring threshold was decreased to a score of 2 or higher. These patients were referred from various settings to include EDs, urgent cares, primary care clinics, and COVID-19 testing tents. All patients who received bamlanivimab had a follow-up telehealth visit within 48 hours after infusion. The control group was recommended to follow up with their primary care provider, but there was no assurance this was followed.

All patients included in the study needed a documented referral form (Fig. 1) completed by a provider within the healthcare system before January 29, 2021, to confirm eligibility for bamlanivimab. Patients included in the control group did not receive any monoclonal antibody therapy for COVID-19, despite having a referral form completed, a recorded risk score of 2 or higher, symptoms for 10 days or less, and a confirmed positive SARS-CoV-2 test result. To confirm that patients did not receive monoclonal antibody, electronic medical records were reviewed, including those available via Chesapeake Regional Information System for Patients, a Maryland state–designated health information exchange. Reasons for not receiving bamlanivimab could not be ascertained based on chart review. Of note, there was capacity to treat these patients. The treatment group comprised patients who received bamlanivimab before January 29, 2021, in our healthcare system, and had a risk score of 2 or higher, did not have symptoms for greater than 10 days, and had a documented positive test result.

Data Collection and Study Variables

Patients were referred for monoclonal treatment between November 23, 2020, and January 28, 2021. A database of all of the patients referred for monoclonal antibody treatment during this time period was reviewed to identify eligible patients. Those patients who were referred and received the monoclonal antibody treatment were labeled as the treatment group, whereas those who did not receive the monoclonal treatment but were referred were labeled as the control group. A secure electronic data collection spreadsheet was designed to collect all relevant deidentified variables for both groups. Specific data elements were acquired via full review of all available electronic medical records. Data concerning subsequent visit to the ED, hospital, and/or death rates were collected by reviewing the patient charts and by looking through Chesapeake Regional Information System for Patients data for outside hospitalizations. Data such as the number of days since onset of symptoms at time of infusion and their score at time of referral were found in the referral database, as this could easily be pulled from the medical record.

Outcomes

The primary outcome of this study was rate of hospitalization (observation and full inpatient stay) between the treatment and control groups. Secondary outcomes included rate of ED visits (without hospitalization) and death rates between the treatment and control group. Other secondary outcomes within the treatment group included comparing rate of hospitalization and death based on their underlying comorbidities (ie, their score) and on number of days from infusion since onset of symptoms.

Statistical Analysis

Comparison of proportions of categorical variables between the control and treatment groups is conducted using the χ2 test. Continuous variables are not normally distributed; hence, comparison is conducted using a nonparametric Kruskal-Wallis test. Median and interquartile range (IQR) are presented for both along with mean and SD. Statistical testing was done using R version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria). This study was performed with data collected after institutional review board approval.

RESULTS

Data were collected and reviewed from 438 patients referred for monoclonal antibody treatment with bamlanivimab during this period. Of these, 253 patients received the bamlanivimab infusions (treatment group), whereas 185 patients were referred but did not to receive the monoclonal infusion (control group).

The demographics of the patient population are presented in Table 1. The 2 groups did show a statistically significant difference, with the treatment being performed for a slightly older population (P = 0.05). In addition, there were some statistical differences in the race of the two groups. Lastly, the treatment group had a statistically higher percent of patients with diabetes.

TABLE 1 - Demographics of COVID-19 Patients Referred for Bamlanivimab
Total (n = 438) Received Bamlanivimab (n = 253) Did Not Receive Bamlanivimab (n = 185) P
Age, y
 <65 168 (38.4%) 87 (34.4%) 81 (43.8%) 0.0458*
 ≥65 270 (61.6%) 166 (65.6%) 104 (56.2%)
Sex
 Women 260 (59.4%) 152 (60.1%) 108 (58.4%) 0.7204
 Men 178 (40.6%) 101 (39.9%) 77 (41.6%)
Ethnicity
 Hispanic or Latino 19 (4.3%) 13 (5.1%) 6 (3.2%) 0.1544
 Not Hispanic or Latino 343 (78.3%) 203 (80.2%) 140 (75.7%)
 Unknown 76 (17.4%) 37 (14.6%) 39 (21.1%)
Race
 Black or African American 209 (47.7%) 122 (48.2%) 87 (47%) 0.0373*
 White 126 (28.8%) 79 (31.2%) 47 (25.4%)
 Other 71 (16.2%) 41 (16.2%) 30 (16.2%)
 Unknown 32 (7.3%) 11 (4.3%) 21 (11.4%)
Medical comorbidities
 BMI ≥35 kg/m2 210 (47.9%) 121 (47.8%) 89 (48.1%) 0.9535
 Chronic kidney disease 49 (11.2%) 29 (11.5%) 20 (10.8%) 0.8308
 Diabetes 225 (51.4%) 121 (47.8%) 104 (56.2%) 0.0827
 Immunosuppressive disease 44 (10%) 26 (10.3%) 18 (9.7%) 0.8508
 Immunosuppressive treatment, active 26 (5.9%) 16 (6.3%) 10 (5.4%) 0.6878
 Hypertension poorly controlled 125 (28.5%) 70 (27.7%) 55 (29.7%) 0.6370
 Cardiovascular disease 106 (24.2%) 66 (26.1%) 40 (21.6%) 0.2811
 COPD or other respiratory disease 53 (12.1%) 30 (11.9%) 23 (12.4%) 0.8554
*Significant at P < 0.05.
COPD indicates chronic obstructive pulmonary disease.

The median scores calculated at the time of their referral for both the treatment and control groups were 3.0 (IQR, 3.0–4.0). The mean (SD) score for the treatment group was 3.8 (1.0), whereas the mean (SD) for the control group was 3.6 (0.9) (P = 0.06). The median numbers of days of symptoms at the time of the referral and scoring were 4.0 (IQR, 2.0–5.0) days for the treatment group and 4.0 (3.0–6.0) for the control group. The mean (SD) numbers of days of symptoms at the time of the referral and scoring were 4.3 (2.2) in the treatment group and 4.0 (2.1) in the control group (P = 0.16).

Of the patients receiving bamlanivimab, 26% patients received bamlanivimab in the ED, whereas the remaining 74% patients received treatment in one of the outpatient monoclonal infusion centers.

Hospitalization rates in the treatment group (observation and inpatient admission) were 6.7% (n = 17) in the treatment group and 14.1% (n = 26) in the control group (P = 0.02) (Table 2). Rates of subsequent ER visit (without admission) were 9.1% (n = 23) in the treatment group and 11.4% (n = 21) in the control group (P = 0.50). Mortality rates among the treatment and control groups were 1.2% and 0.5%, respectively (P = 0.852).

TABLE 2 - Outcomes of COVID-19 Patients Referred for Bamlanivimab
Total (n = 438) Received Bamlanivimab (n = 253) Did Not Receive Bamlanivimab (n = 185) P
Risk score, median (IQR) 3.0 (3.0–4.0) 3.0 (3.0–4.0) 3.0 (3.0–4.0) 0.061
Risk score, mean (SD) 3.7 (1.0) 3.8 (1.0) 3.6 (0.9)
ED FU Visit, n (%) 44 (10.0) 23 (9.1) 21 (11.4) 0.538
IP OBS FU care visit, n (%) 43 (9.8) 17 (6.7) 26 (14.1) 0.017
Days of SXS at time of scoring*, median (IQR) 4.0 (2.0–6.0) 4.0 (2.0–5.0) 4.0 (3.0–6.0) 0.139
Days of SXS at time of scoring, mean (SD) 4.8 (28.9) 5.5 (38.0) 4.0 (2.1)
Death, n (%) 4 (0.9) 3 (1.2) 1 (0.5) 0.847
Days of SXS at time of infusion, median (IQR) 6.0 (4.0–8.0) 6.0 (4.0–8.0) NA NA
Days of SXS at time of infusion, mean (SD) 5.9 (2.4) 5.9 (2.4) NA NA
*At the time of screening for the treatment group.
Significant at P < 0.05.
FU indicates follow-up; IP OBS FU, inpatient or observation follow-up; SXS, symptoms; NA, not applicable.

Patients who received post–follow-up care that was not related to COVID-19 were not included in the follow-up of care rates but were included in the overall control or treatment groups.

DISCUSSION

An integrated protocol was developed across our health system's large distributed care delivery network to identify qualifying patients most at risk for progression to severe illness, by virtue of their risk factor profile, and to rapidly treat those patients with monoclonal antibody infusion. This study found that among patients with COVID-19, who were identified as qualifying for treatment based on their risk factor score, subsequent hospitalization rates were lower among patients who received bamlanivimab infusion, compared with those who did not. Neither ED visits nor death rates were impacted by bamlanivimab infusion. With the rapid implementation of monoclonal infusion for COVID-19 across a large hospital system, participants who received bamlanivimab had similar outcomes to those described in other studies.1,5

Clinical trials have demonstrated that patients with recently diagnosed mild to moderate COVID-19 may benefit from early intervention with monoclonal antibody therapy. Bamlanivimab infusion has been shown in these trials to improve symptom scores early in the course of the illness and to translate to decreased rates of hospitalization.1 In addition, a similar study was recently published by Northwestern University, showing a decreased hospitalization rate in a Bamlanivinab treatment group compared with a control group.5 The Northwestern scoring system differed from ours—in particular, extra points were not given to those 65 years and older or with BMIs >35 kg/m2. The Northwestern study also did not use their scoring system to determine distribution of the drug because of demand not exceeding supply. When comparing their control group with the bamlanivimab arm, their magnitude of difference in hospitalization rates was less than this study's hospitalization rates. This may be indicative of our hospital system's requirement for a set score needed for monoclonal antibody referral.

The opportunity to compare patient outcomes among individuals with similar risk factor profiles, based on using a scoring rubric implemented before the roll out of bamlanivimab infusion and the willingness of the patient to receive the infusion, strengthened the study findings as the patients in the receipt/nonreceipt groups did not differ by demographics or risk factor score.

This study describes the development of our scoring rubric, easily implemented in multiple health care settings, including primary care practices, urgent care centers, and EDs, to identify patients who may benefit from monotherapy for COVID-19. Existing literature suggests that advanced age (≥65 years) and morbid obesity (BMI ≥35 kg/m2) are the risk factors most associated with increased rates of hospitalization among patients with COVID-19. For this reason, these risk factors were prioritized and weighted more heavily in our scoring rubric. This serves as a proof of concept, one that can be implemented in the future for newer monoclonal antibodies in the treatment of COVID-19.

Among the secondary outcomes, our study did not find statistically significant differences between the treatment group and the control group in rates of subsequent ED visits (without hospitalization) or death rates.

Limitations

This study had several limitations. First, it was a retrospective cohort study comparing patients who received bamlanivimab therapy with patients who were referred for bamlanivimab but did not proceed with receiving an infusion. This introduces possible confounders, as the reasons for why patients declined to pursue treatment were not ascertained.

Second, because there is no objective assessment of symptom severity in our protocol, we cannot directly assess the impact of treatment on amelioration of symptoms.

Third, although there are 2 combination therapy monoclonal antibody agents with EUA approval, bamlanivimab/etesevimab (LY-CoV555/LY-CoV016; Eli Lilly and Company) and casirivimab/imdevimab (REGN-COV2; Regeneron Pharmaceuticals), our study focuses on monotherapy with bamlanivimab. Bamlanivimab as a monotherapy was the first monoclonal antibody regimen available and thus is the agent that we used in our protocol. These combination therapies have been shown to have even greater ability to reduce rates of COVID-19–associated hospitalizations and ED visits.6

Lastly, this study was done before the widespread circulation of SARS-CoV-2 variants. As of March 25, 2021, the US Department of Health and Human Services stopped the distribution of bamlanivimab when administered alone because of a sustained increase in SARS-CoV-2 variants that are resistant to bamlanivimab when administered alone. Furthermore, on June 25, 2021, US health officials paused the distribution of Eli Lilly's COVID-19 dual-antibody therapy—bamlanivimab and etesevimab—as it failed to show effectiveness against the coronavirus variants that were first identified in Brazil and South Africa. Hence, the focus of this article is highlighting the unique and rapid implementation process stood up in a large healthcare system.

Strengths

These results demonstrating decreased rates of hospitalization among patients with mild to moderate COVID-19 after treatment with monoclonal antibody infusion are consistent with existing literature. The protocol used here, using a risk factor scoring rubric with predetermined treatment threshold to allow for prioritization of patients at greatest risk for progression to severe disease, is a novel approach. This scoring rubric and the associated EHR-based referral and treatment pathways were adopted at nearly all points of entry into our health system, including primary care practices, urgent care centers, and EDs. This allowed for early identification of those patients most likely to benefit from monoclonal antibody therapy and a coordinated approach for rapid treatment with monoclonal antibody therapy. Referral was expanded to providers not affiliated with our health system to ensure therapy was available to high-risk individuals in an equitable manner.

CONCLUSIONS

Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab monotherapy is effective in preventing subsequent hospitalization. Development of a simple and easily reproducible protocol to identify patients at greatest risk for progression to severe illness, based on their risk factor profile, is possible and can assist in the rapid identification and treatment of patients from across a large distributed care delivery network that are most likely to benefit from monoclonal antibody therapy.

ACKNOWLEDGMENTS

We thank Stephen Evans, MD; Karol Edwards, RN; Xavier Owens, MHSA; Agisi Makrodimitris MSPAS, PA-C; Rollin J. “Terry” Fairbanks, MD; Christina Hughes, RN; James Welsh, MD; Traci Anderson, RN; Stephanie Schneider; Maria Burnette; Olakorede Akintelure, MHA; Stephen Baur, DPT; Lynette Godhard, RN, BSN; Jill Palinkas, CPC; Marybeth Kazanas, PharmD; Susan Whitecotton; and Margaret Breakenridge for their efforts in establishing the monoclonal antibody infusion program.

REFERENCES

1. 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;384:229–237.
2. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19. N Engl J Med. 2020;384:238–251.
3. Williamson K, Tewarson H. Increasing utilization of COVID-19 monoclonal antibodies: considerations and promising practices for states. 2021. National Governor's Association. Available at: https://www.nga.org/center/publications/increasing-utilization-monoclonal-antibodies/. Accessed July 23, 2021.
4. Fineberg HV. “Rapid Expert Consultation on Allocating COVID-19 Monoclonal Antibody Therapies and Other Novel Therapeutics (January 29, 2021).” National Academies of Sciences, Engineering, and Medicine. Washington, DC: The National Academies Press; 2021. doi: 10.17226/26063.
5. Kumar RN, Wu EL, Stosor V, et al. Real-world experience of bamlanivimab for COVID-19: a case-control study. Clin Infect Dis. 2021;ciab305. Available at: https://doi.org/10.1093/cid/ciab305. Accessed May 4, 2021.
6. 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.
Keywords:

COVID-19; monoclonal antibody therapy; infusion

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.