Nurse Anthony Bono works with equipment in the LTC Charles S. Kettles VAMC Emergency Department. The VAMC became one of the first to distribute monoclonal antibodies, which . give high-risk patients’ immune system a “boost” to fight off severe illness resulting from COVID-19 infection. Photo from Ann Arbor, MI, VAMC public affairs
ANN ARBOR, MI — As emergency departments around the country struggled to get through the day during the recurrent surges of the COVID-19 pandemic, the emergency medicine team at the LTC Charles S. Kettles VAMC here did something extraordinary—they sought out more patients to treat.
“We wanted to be able to utilize these monoclonal antibody products that had received emergency use authorizations [from the Food and Drug Administration] to reduce the risk of people having more severe outcomes from COVID infections and reduce the healthcare burden associated with hospitalization,” said Andrew Siler, PharmD, BCPS, clinical pharmacy specialist in the VA Ann Arbor Health System (VAAAHS). “So, we stood up a clinic where we could infuse these medications.”
Setting up the service offered a lifeline to many patients. At the time of their authorizations, “treatment with monoclonal antibodies (mABs) had been shown to reduce the risk of COVID-19 hospitalizations and death by at least 70% in people who showed mild or moderate symptoms,” the TRICARE military health plan noted. Monoclonal antibodies are molecules developed in a laboratory that act like naturally produced antibodies to prevent the SARS-CoV-2 virus from attaching to cells and causing COVID-19. Another VA facility that set up an infusion center in December 2020, the Robert J. Dole VAMC in Wichita, KS, reported a more than 97% success rate in preventing hospitalizations through last August.
A letter to the editor in the January 2022 issue of Infectious Diseases in Clinical Practice showed higher rates of hospitalization and one death at the Northport, NY, VAMC. The Northport Infectious Diseases team treated 37 veterans between Dec. 1, 2020, and May 31, 2021, with either casirivimab/imdevimab or bamlanivimab. Of those, nine patients continued to worsen after the therapy and required intravenous remdesivir and steroids. A patient with non-Hodgkin lymphoma who required remdesivir and baricitinib died. None of the veterans who had been vaccinated required additional treatment. Ultimately, 24% of those who received mAB required hospitalization.1
Multiple Challenges
While Siler’s description makes establishing the service sound simple enough, the task presented significant challenges. “First, we had to deal with all the infection concerns and the logistical pieces of getting people in who were COVID positive and met our criteria,” Siler told U.S. Medicine. The emergency department (ED) team pulled the VAMC facility wide COVID-positive list from the electronic health record system and then screened the patients to see if they qualified for the antibody therapy.
“We also publicized the service to the primary care team within our VA network, so that they were also aware that we were able to potentially deliver the monoclonal antibodies,” said Emergency Department Director Paul Kim, MD. “So, if a veteran got tested outside, in the community, and had a positive result and they then notified their primary care doctor, they would notify us.”
The criteria for use of initially required patients to be within 10 days of diagnosis with mild to moderate symptoms and at high-risk of developing severe COVID-19 but not yet hospitalized. High-risk factors include age greater than 65 years, overweight, pregnant, chronic kidney disease, diabetes, immunocompromised. Individuals aged 55 or older who had underlying lung disease, heart disease or hypertension also were eligible. [The FDA expanded the criteria subsequently to include treatment of asymptomatic patients and COVID-positive individuals’ close contacts who were at high-risk of severe disease and not fully vaccinated or vaccinated but immunocompromised.]
Coordinating Care
If veterans meet the criteria, the team calls them to discuss the therapy and arranges for them to receive the treatment in the ED. The team screens patients, supervises the hourlong infusions and monitors the veterans for an additional hour for reactions, all while addressing the regular patient load of the department and managing infection control concerns.
Because the team started mobilizing to treat veterans as soon as the monoclonal antibodies received FDA emergency use authorization (EUA) in December 2020, they needed to work out all the kinks from scratch. To minimize the spread of infection, the team “dedicated specific negative pressure rooms that had all the precautions already in place for COVID and then spread out the arrival times throughout the day to not overwhelm our own ED and be able to deliver the treatment in a measured way so we could maintain all our various efforts,” Kim explained.
The quick start enabled the team to get a jump on administering the treatments. “That’s what has allowed us to give more monoclonal antibodies than anyone else in the VA,” Kim noted. The clinic was up in time to serve veterans during the surge in December 2020-January 2021 and then meet the alpha variant’s demands last spring with confidence, even as the recommended treatments changed. In April 2021, the FDA revoked the EUA for bamlanivimab because SARS-CoV-2 had developed resistance. In late June, the agency recommended against using the combination of bamlanivimab and etesevimab, as it was ineffective against both the beta and gamma variants.
After a dip in demand last summer, the team rose to the challenge of protecting veterans again as delta wreaked havoc late last summer. Casirivimab/imdevimab have proved ineffective against omicron, forcing yet another change. The only antibody treatment shown to work against the highly contagious variant is sotrovimab, which has been in such short supply that it has been limited nationwide to use in only the most vulnerable symptomatic individuals. Sotrovimab received EUA in May and is only authorized for use in COVID-positive patients.
With the shortage of sotrovimab and “in concert with various groups, to include Infectious Disease, COVID Treatment Options, Scarce Resource Allocation, and Ethics Committees, we adjusted the criteria to target the highest of high risk patients with our few doses,” Siler added. “Fortunately however, contemporaneously with the antibody shortage, oral antiviral therapies (Paxlovid and molnupiravir) to treat COVID become available, which supplemented our outpatient treatment options just as the antibody supply faltered, and allowed us to maintain our aggressive approach of reaching out and treating our veterans as before. We actually just used the same model we had set up for identifying and treating our antibody patients, and applied that to the oral therapies now available.”
As the pandemic enters its third year, Siler said, “in many ways, we’re becoming more used to this than we probably would want to be.”
- Mann I, Froehlich M, Bailey L, Psevdos G, Lobo Z. Monoclonal Antibody Therapy for US Veterans with COVID-19. Infectious Diseases in Clinical Practice. Jan. 2022;30(1):e1086. Doi: 10.1097/IPC. 0000000000001086