The end of the year is fast-approaching and with it comes several strides in the development of vaccinations for COVID-19, but there are still many hurdles to overcome.
On December 1, the Advisory Committee on Immunization Practices (ACIP) recommended interim guidance for federal, state, and local jurisdictions on allocation of the initial doses of COVID-19 vaccines that are expected to become available within the coming weeks pending approval by the US Food & Drug Administration (FDA). On December 10, the FDA will consider Emergency Use Authorization (EUA) for the Pfizer-BioNTech coronavirus vaccine for people aged 16 years and older and on December 17 EUA for the Moderna vaccine for people aged 18 years and older. Approval is expected given the high efficacy rates of nearly 95% in preventing disease reported by both vaccine manufacturers (and the 100% efficacy in preventing severe disease reported for the Moderna vaccine) as well as no significant safety concerns.
The most recent assessment of the vaccines by the Vaccines and Related Biological Products Advisory Committee, which will be submitted to the FDA, found that injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), chills (31.9%), and fever (14.2%) were the most common side effects in vaccinated volunteers, with more severe reactions in 2.8% of people older than aged 55 and 4.6% in those under that age. Serious adverse events occurred in both the vaccine and placebo arm, with four cases of Bell’s palsy in the vaccine arm and 64 cases of lymphadenopathy in the vaccine group and six in the placebo group.
In its recommendations, the ACIP prioritizes health care personnel and long-term care facility residents (phase 1a) as the populations to receive the initial vaccine doses. As more vaccine doses become available, the next round would go to essential workers (phase 1b) and then adults with high-risk medical conditions and those older than 65 years (phase 1c).
For all three phases, states and local jurisdictions will need to make some tough decisions based on the amount of vaccine doses available. The ACIP made their recommendations based on an estimated availability of 40 million doses of the vaccine for initial distribution by the end of 2020—an amount that would basically cover 20 million people based on the two-shot regimen needed. It is estimated, however, that 24 million people comprise these high-priority groups. New almost daily reports also indicate that States will be allocated less than the expected doses and many are scrambling to adjust distribution plans.
Starting in 2021, the estimated available doses will ramp up to a 60 million (covering 30 million people) in January and 100 million (50 million people) in February. However, defining exactly who is an essential worker and capturing everyone who may fall under that category for vaccination during phase 1b will likely outnumber the amount of vaccine available. Similar problems may face phase 1c given the high numbers of older people with high-risk medical conditions.
The projected higher demand than supply at least initially will require judicious allocation of the available vaccine doses within the populations designated—referred to as sub-prioritization during the ACIP discussions. In addition, equitable distribution of the vaccine, for example, to community and rural clinics will need to be addressed particularly given the challenges and expense of the cold storage needed for both the Pfizer-BioNTech vaccine (requiring -70⁰C) and Moderna vaccine (requiring -20⁰C).
As demanding as the distribution issues are, equal to and perhaps more challenging is convincing people to get vaccinated. Recent data from a study funded by the Yale Institute for Global Health looking at the determinants of COVID-19 vaccine acceptance in the United States shows that 67% of people surveyed would take the vaccine, but acceptance varied based on age, ethnicity, educational level, and employment status. Even health care workers are expressing concerns about getting the vaccine, with only 63% saying they would get the vaccine in a survey conducted by the Centers for Disease Control and Prevention (CDC).
Underscoring that sub-prioritization may be necessary initially if allocation of doses do not equal the number of people in the priority groups, Lynn Bahta, immunization clinical consultant for the Minnesota Department of Health, and a board member of ACIP, echoed suggestions from the ACIP. “Similar to how the ACIP has thought through this, the vaccine needs to be directed toward those with a higher risk of exposure to COVID-19 disease and to those who are more severely impacted if they get COVID-19.”
As discussed during the December 1 ACIP meeting by Sara Oliver, MD, MSPH, an epidemic intelligence service officer with CDC’s Division of Viral Diseases, if sub-prioritization is needed for health care workers, groups to consider sub-prioritizing may include personnel with direct contact with patients who are not able to telework, those working in residential care or long-term care facilities, and those without known infection 90 days prior to vaccination.
Dr Oliver emphasized the importance of taking into account the potential for transient reactogenicity following vaccination and suggested ways to ensure sufficient staffing such as staggering vaccination of personnel from similar units or positions and planning for personnel to have time away from clinical care if they experience post-vaccination symptoms. Once the vaccine becomes available, the CDC will be providing further guidance on how to handle systemic symptoms post-vaccination in health care personnel, according to Dr Oliver.
For long-term care facilities, the ACIP prioritizing skilled nursing facilities and then broadening out to other types of long-term care settings including assisted living facilities, residential care communities, intermediate care facilities for people with developmental disabilities, and State Veterans Homes.
Susan Cantrell, chief executive officer of the Academy of Managed Care Pharmacy (AMCP), said that AMCP has been working closely with partners across the spectrum of pharmacies, including community, long-term care, hospital, and others, to address supply chain issues. She cited supply chain challenges early in the pandemic caused by potential medications of COVID-19 that led to the need for close monitoring of supplies. “Supply chain [issues] are part of what pharmacists do and when the vaccine becomes available there will be challenges but we know by work done already by our members that we are ready to address these challenges,” she said.
One challenge will be equitable distribution of the vaccine. Citing the recent surge of infection in rural communities as well as the ongoing disproportionate infection rates in people of color, Ms Cantrell emphasized the importance of making sure that rural and community clinics get their fair share of the vaccine and that doses do not all go to the larger hospital systems. “All of this has to be considered as we look at how we equitably and fairly distribute this vaccine,” she said.
Ms Bahta also said that equity in vaccine distribution as a top priority, citing groups most impacted by severe outcomes from COVID-19 including the elderly, Black, Latino, and indigenous populations.
One population that will need additional consideration is pregnant or breastfeeding women. No safety data are yet available on the use of vaccines made from the mRNA technology used in the Pfizer and Moderna vaccines for this population of women. As cited in the ACIP discussion, 75% of the health care workforce are women and about 330,000 could be pregnant or recently postpartum at the time of vaccinations. The need to protect these women is underscored by data showing the potentially increased risks of severe maternal illness and preterm birth due to COVID-19 disease. It is anticipated that further guidance on vaccinating these women will come once phase 3 data is available.
Messaging: Building Confidence in Vaccine Safety
A critical component of vaccine deployment will be ensuring that people actually get vaccinated. The rapid development-to-distribution evolution of these vaccines has sparked a lot of discussion of safety issues, some of which may be reasonably tied to uncertainty given the lack of longer-term safety data as well as issues related to the new mRNA type of technology used to develop these vaccines. Other safety concerns may be related to more traditional antivaccine concerns based on a distrust in the medical system or care providers.
As discussed in a recent study published in Vaccine, regarding vaccine hesitancy and health care providers, health care providers remain the most trusted advisors influencing vaccination decisions for their patients but face challenges not only by the increased number of people questioning vaccine safety but by the inadequate information they have to address vaccine questions.
Drew Weissman, MD, PhD, department of medicine, University of Pennsylvania, Philadelphia, PA, who studies RNA and innate immune system biology and its application to vaccine research and gene therapy, explained that the science behind the mRNA technology used to develop the COVID-19 vaccines has been studied for years and has shown 100% protection against a number of diseases in 30 different vaccines tested in animals. Although humans are different than animals, he was not surprised that the Pfizer and Moderna vaccines show 95% efficacy.
Regarding safety, Dr Weissman said that no long-lasting adverse effects have been seen in over 35,000 people receiving mRNA vaccines in clinical trials for diseases such as influenza and COVID-19. “What we see are local effects, such as a sore arm or swelling, or redness,” he said, adding that a subset of patients get flu-like symptoms that clear up in a day or two.
“I look at this as a risk-benefit [decision]. The risk of death from COVID-19 is 0.5% to 25% depending on the population, [whereas] there is no risk of the vaccine so far. So I think it is an easy calculation,” he said.
Going forward, gathering safety data will be critical. One important role for health care providers will be to help collect that data by reporting adverse events through the Vaccine Adverse Events Reporting System (VAERS), as well as encourage patients to register to use a new smartphone-based active surveillance system called v-safe that allows tracking adverse events post vaccination. Ms Bahta said that in Minnesota, the Department of Health is continuously reminding clinics to report adverse events to VAERs and will be encouraging vaccinators and vaccinated persons to participate in v-safe.
Editor’s Note: The information in this article was accurate at time of publication. Please always refer to the FDA and appropriate agencies for the most up-to-date information regarding COVID-19 and its associated treatments and vaccinations.