As Vaccine Rollout Stalls, Move Monoclonal Antibodies Into COVID Fight

Our great hope of snuffing out the coronavirus disease 2019 (COVID-19) pandemic with vaccinations in early 2021 appears more and more to be a bridge too far. In California, the health care system is reaching a breaking point, with shortages in oxygen and reports of ambulances being turned away, they simply cannot keep up with the patient load. The recent plans of the states for opening mass vaccination centers once they receive the vaccines held in the nation’s reserve, may be ill-founded. Secretary Alex Azar recently announced that “because we now have a consistent pace of (vaccine) production, we can now ship all of the doses that had been held in physical reserve.” But what was not stated was that there were no reserves. The fallback plan is those who need a second dose will be prioritized over the administration of first dosages. Thus, our vaccine program is at risk of grinding to a snail’s pace.

Kevin Kavanagh, MD

The United States is dependent upon distribution as soon as the vaccines are manufactured. In December 2020, the United States’ Government signed an important contract to purchase an additional 100 million doses (enough to vaccinate 50 million individuals) of the Pfizer/BioNTech vaccine, but delivery for all of the doses is not expected until July 2021.

As of January 16, 2021, only 39.4% of the 31.2 million allocated vaccine doses have been placed in arms. The original goal was to vaccinate 20 million citizens by the end of 2020.

It needs to be remembered that vaccinations, not vaccines, are what prevents disease. Because of the slow pace of vaccinations, on January 12, 2021 the Department of Health and Human Services (HHS) has recommended that those eligible for vaccines be expanded down to age 65 and those patients with co-morbidities.

Until vaccines become widely available, it is imperative that those at high risk for severe COVID-19 be offered monoclonal antibody therapy. Two companies make this product, Eli Lilly and Regeneron. The initial reported results by Eli Lilly were a phenomenal 72% reduction in ER visits and hospitalizations. President Trump, Governor Chris Christie and Rudy Giuliani all have received monoclonal antibody treatments, and despite their being at high risk, obtained excellent results.

The FDA reported the results of a double-blind clinical trial using Regeneron’s monoclonal antibody cocktail which produced a marked reduction in hospitalizations and emergency room visits which occurred in 3% of casirivimab and imdevimab-treated patients, compared to 9% in placebo-treated patients.

So far, the use of monoclonal antibodies has not been a priority in the United States’ COVID-19 response, and the medication has largely gone unused, with 80% of the 600,000 doses still “sitting on shelves.” Monoclonal antibodies need to be given within 3 days of diagnosis, and to those who are at high risk for severe COVID-19. This includes the following categories of patients:

• Have a body mass index (BMI) ≥35
• Have chronic kidney disease
• Have diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment
• Are ≥65 years of age
• Are ≥55 years of age AND have
-- cardiovascular disease, OR
-- hypertension, OR
-- chronic obstructive pulmonary disease/other chronic respiratory disease.
• Are 12–17 years of age AND have
-- BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm , OR
-- sickle cell disease, OR
-- congenital or acquired heart disease, OR
-- neurodevelopmental disorders, for example, cerebral palsy, OR
-- a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
-- asthma, reactive airway or other chronic respiratory disease that requires daily medication for control.

Monoclonal antibodies are not felt to be effective in hospitalized patients. There are 3 possible reasons for their non-usage. First, the medication should be given within 3 days of diagnosis. In many areas of the United States, a laboratory PCR test is taking far too long to receive results to allow for usage of monoclonal antibodies. One needs to make sure test results are back in 2 days. If a patient is newly symptomatic, the viral load will probably be high and rapid testing (antigen or PCR) may also be an option. Second, although the Federal Government is providing the medication for free, some facilities are charging for its administration, which can cost “well over” $1000. Even patients with private insurance may have to pay a hefty sum after co-pays and deductibles are billed. Finally, too many patients still think SARS-CoV-2 is not a serious infection and some even feel it is a hoax.

Needless to say, with the new South African and Brazilian strains threatening the US, we must stop the spread of this virus. Many fear these strains may be resistant to monoclonal antibodies and render the vaccines less effective. (Complete resistance to vaccines probably will not occur, since vaccines produce a plethora of different antibodies to the SARS-CoV-2 spike protein.)

Viral resistance to monoclonal antibodies was even mentioned in Eli Lilly’s initial investor’s report. “Viral RNA sequencing revealed putative LY-CoV555-resistance variants in placebo and all treatment arms. The rate of resistance variants was numerically higher in treated patients (8 percent) versus placebo (6 percent).”

The good news is that multiple COVID-19 vaccines are in the pipeline. One of which is being developed by the US Army and has been reported to produce “very good responses” to a wide variety of coronaviruses including SARS-CoV-2 variants. Thus, we need to maintain our resolve and follow public health advice. When patients become infected, they need to have ready access to COVID-19 testing with results in 48 hours or less. If positive, we need to act and utilize the nation’s supply of monoclonal antibodies while they are still highly efficacious. This will not only help prevent a collapse of our health care system but also buy us precious time to expedite vaccine production and distribution.

If you suspect you may have COVID-19, obtain a test as quickly as possible and make sure you will receive the results within 2 days. And if positive and at high risk for severe COVID-19, ask your doctor about referral to receive the antibody treatment.

If you are an infection preventionist, locate testing centers with adequate turnaround times. If none are available, advocate with your hospital leadership to create these resources. And above all educate primary health providers on the importance of utilizing this important medication to prevent hospitalizations from severe COVID-19.

To locate a facility, the Dept. of Health and Human Services has posted a medication locator at: https://combatcovid.hhs.gov/ Then click on the "Find Infusion Locations" screen button.