Along with the Baby Yoda plush dolls, Gravity Blankets and Ninja Air Fryers loaded on UPS and FedEx planes and trucks this Christmas season was the most desired gift of all: COVID-19 vaccines, from manufacturers Pfizer-BioNTech and Moderna. The Pfizer vaccine, shipped in special boxes to keep doses colder than the surface of Mars, was first, arriving in Arkansas on Dec. 14.
Like other coveted presents, however, the vaccines were in short supply, so the government, with input by a panel of health experts and the nod from the governor, chose who’d be first in line: health care professionals and others who attend COVID-19 patients and staff and residents of long-term care facilities.
The first shipment, from Pfizer, was of 25,350 doses and 18,525 more were promised, an amount less than expected. An estimated 51,000 doses of Moderna were delivered before 2020 came to a close. Pfizer shipments went directly to 18 hospitals and five pharmacies across the state. Moderna shipments went to national delivery hub pharmacies Walgreens and CVS (as well as a portion for the state) for use in long-term care facilities.
Finally, a year after the novel coronavirus leapt from the wild to infect humans with a disease they had no defenses against, there was a way to fight back. But getting the weapons into the arms of the general public will take a while. We’ve entered a second year of mask-wearing and social distancing to protect ourselves and others from a virus that has killed more than 300,000 people in the U.S., including more than 3,000 in Arkansas.
Pfizer and Moderna’s were but two of 61 vaccines in clinical trials in mid-December worldwide. Only six other companies had produced vaccine in use elsewhere, in China, Russia and the United Arab Republic. Operation Warp Speed, the federal Health and Human Services project to develop and purchase vaccine, invested in six for use in the states: In addition to Pfizer (which is selling to the U.S. but did not use tax dollars for development) and Moderna, four other companies have received billions of tax dollars to get their vaccines developed and shipped: Johnson & Johnson, AstraZeneca, Novavax and Sanofi-GlaxoSmithKline.
It’s anyone’s guess when these four vaccines will get emergency approval from the Food and Drug Administration and hit the market. Johnson & Johnson, which launched a final phase 3 trial in December to test the efficacy of two doses over one, seems likely to be the next to seek authorization. The company has said it will begin round-the-clock manufacture this month, pending FDA approval. Novavax has finished phase 3 trials in the U.K. and was preparing to start phase 3 trials in the U.S. in December.
AstraZeneca, which is working with Oxford University in Great Britain, has had several stumbles, including inaccurate results stemming from a mistaken measurement and an efficacy rate ranging from 70% to 90%, depending on administration. It will continue to do research and in December announced it was joining forces with the Russians in their Sputnik V vaccine to see if combining the vaccines improved efficacy.
Sanofi-GlaxoSmithKline, which planned to move to phase 3 in December and have vaccine by spring, has backed off that schedule because of disappointing efficacy results; it now gives late 2021 as its availability date.
The U.S. is paying Pfizer $1.9 billion for 100 million doses, which is enough for 50 million people. It passed up Pfizer’s offer to provide 100 million more, ostensibly because the government thought it more prudent to bank on several vaccines. Moderna, which received nearly $1 billion from the government in development support, entered into a $1.5 billion contract for 100 million doses in August. In December, the U.S. decided to buy 100 million more.
The 300 million doses would be enough for 150 million people, or 6 in 10 adult Americans. Neither company, which will sell vaccines worldwide, has divulged how it will divvy up global production in 2021.
The Arkansas Department of Health’s most recent tally, in 2018, of licensed health professionals put the number at nearly 90,000, and a spokesman estimated there are 45,000 residents and staff at nursing homes now. Both Moderna and Pfizer’s vaccines require two doses, so, in the admittedly unlikely case all health care professionals and long-term care individuals volunteered to be vaccinated, 90,000 Moderna doses (for long-term care facilities) and 180,000 Pfizer doses (for medical personnel) would be needed.
But the state’s top priority group, based on those of the Centers for Disease Control and Prevention — Phase 1-A — also includes hospital employees who come in contact with COVID-19 patients, such as respiratory technologists, medical assistants who assist in COVID-19 testing, housekeepers, meal servers and others who provide support. That adds the need for tens of thousands of more doses of vaccine.
Dr. Jennifer Dillaha, the medical director for immunizations at the Arkansas Department of Health, said she expects it will take “several weeks” to vaccinate all who fall in Phase 1-A. The state’s phases, as they stand now:
1-A: Health care workers, beginning with those in highest-risk settings, long-term care residents. Large hospitals are having vaccine delivered directly; smaller ones are supplied by pharmacies. Health care workers not affiliated with hospital systems but considered priority workers and some first responders will be vaccinated at pharmacies and health units.
1-B: Persons over 75 and front-line essential workers, such as first responders, teachers and other K-12 school employees, meat-packing workers, correctional workers, postal workers, grocery store workers and others. However, until there is a greater amount of vaccine, certain of these categories will go first. The CDC’s Advisory Committee on Immunization Practices made the recommendation Dec. 20; states will adjust to meet their needs. Their shots will come from pharmacies and clinics; valid I.D. will serve as a prescription for essential workers, according to Arkansas Secretary of Health Dr. Jose Romero. The health department has not yet estimated how many Arkansans will be included in 1-B.
1-C: Persons at risk for severe COVID-19 disease, chronic health conditions or over age 65 and essential workers not covered during in 1-B vaccinations. Pharmacies and clinics, including local health units, will provide vaccines.
2: The rest of us, perhaps by summer 2021, Dillaha estimates. As more vaccines are produced, they will move into the regular supply chain. It’s not known how much the federal government will continue to buy, but vaccines will remain free (though an administration cost may be charged).
Once there is enough vaccine, the ADH may hold mass vaccinations in every county, as it does for influenza. In Pulaski County, it’s likely to be at the State Fairgrounds.
Until then, people who test positive for the virus and whose disease has not progressed may be eligible for infusions of monoclonal antibodies, two forms of which are available, to lessen severity of disease. Operation Warp Speed has invested in their manufacture as well, but like vaccine, supplies are thus far limited.
If the country is to achieve herd immunity — giving the virus fewer people to infect and robbing it of its audience — experts say 70% of the population will need to be vaccinated. Dr. Anthony Fauci, the national face of the fight against the virus and ignored adviser to the president, has put that percentage at 75%, but has also said reaching 50% would help slow spread.
What does that mean for Arkansas, where between only 40% and 50% of the population typically choose to get vaccinated for influenza? It means the health department is going to have to pull together an army of folks to get the word out that the vaccine is safe.
By the time the novel coronavirus had spread to the U.S. in January 2020, Chinese scientists had already sequenced the genome of SARS-CoV-2. That work, and the fact that vaccine manufacturers had already been working on coronavirus vaccines in response to earlier outbreaks of similar viruses that caused SARS and MERS, gave science a running start.
The swift development of the vaccine and the name of the government apparatus that oversaw it — Operation Warp Speed — has given some people pause. Health secretary and ADH director Dr. Romero, who as chairman of the CDC’s Advisory Committee on Immunization Practices works closely with the Food and Drug Administration on safety and efficacy and has examined the data from vaccine clinical trials, has sought to reassure people that authorized vaccines are and will be safe, saying there has been “no compromise” at any point of development. In interviews with the Arkansas Times and the national press, he’s emphasized he received no pressure from either the Trump administration or pharmaceutical companies to deem the vaccines safe and has explained that the FDA will continue to monitor the vaccines for adverse reactions as they become available to many thousands of people. For example, it will no doubt look into the allergic reaction that two health care workers in Alaska suffered from the Pfizer vaccine, a reaction not seen in clinical trials. (Safety fears prompted by the speed with which vaccines are being developed are rational; theories that the vaccines are loaded with soluble microchips so some nefarious agency can keep track of millions of people are loony.)
The health department could not say which areas of Arkansas are the most vaccine hesitant. But it does keep track of the numbers of people who for medical, religious or philosophical reasons are granted exemptions from vaccinating their children. Twenty-seven counties, mainly in Northwest, North-Central and West Arkansas, have exemption rates higher than 1 in 100. Madison County had the highest rate in the 2019-20 school year, with 33 kids per 1,000 exempted. Statewide, 8,753 children were exempted. That doesn’t mean their parents will choose not to be vaccinated, but it is an indicator of distrust.
An October poll conducted by the University of Arkansas for Medical Sciences’ Fay W. Boozman College of Public Health on acceptance of the COVID-19 vaccine found that Black respondents were the least likely to accept the vaccine. It also found a correlation between acceptance of wearing a mask and vaccine acceptance. That finding meshed with a Kaiser Family Foundation poll in December that found that Republicans, African Americans and rural residents were the least likely groups to get a vaccine, though confidence in the vaccine had risen from September, especially among Blacks. About 27% of Kaiser’s respondents remained vaccine hesitant, even if it were free or deemed safe by scientists. Among Republicans, 47% were vaccine hesitant (a view not helped by Fox TV personality Tucker Carlson, who said safety assurances felt “false.”) Only 12% of Democrats were found to be hesitant. Side effects and distrust of the government were most often cited by those opposed.
Dillaha said the health department, including its Office of Minority Health and Health Disparities, is working with Blue Cross Blue Shield, the Immunize Arkansas Action Coalition and other partners across Arkansas to explain, by way of a variety of media and messaging, why the vaccines are safe. The health equity department is developing workshops for influential members of the Black community to help them educate persons in “their social networks” to learn more about the vaccines, she said.
“I would hate for someone to regret they did not get vaccinated,” Dillaha said.
University of Arkansas for Medical Sciences Chancellor Dr. Cam Patterson used a live Twitter chat in December to answer questions from the public about the vaccine. He wasn’t asked if they were safe, but such things as when someone who’d had COVID-19 could be vaccinated (90 days for general public, shorter for health care workers); when UAMS should have sufficient supply for all employees (early January for all providing direct services to COVID patients); what are the possible long-term effects (not known, but other messenger RNA vaccines have been shown to be safe); and when children can get them (unknown). Also: “What do you do if you don’t get your second dose within 21 days?” (“We will track you down. In all seriousness, it’s better late than never, so definitely get the second shot even if you missed the 21-day mark,” he wrote.)
Those who are vaccinated are provided a card reminding them to get the second dose and that it should only be of the vaccine taken, since brands are not interchangeable. The CDC’s cellphone app V-safe allows people to self-report side effects from the shot and will also remind the patient when it’s time to take the second injection. Reminders can also be sent from ADH health units. The state’s vaccine registry, WebIZ, keeps a record of all who’ve been vaccinated.
Patterson was also asked when it would be safe to ditch masks and end social distancing. “When we start getting toward 70% vaccination rates across the community, we should start seeing a downtick in new infections and that’s when I anticipate easing of restrictions. Not until then, though.”
Also unknown: Can an individual who has been vaccinated still transmit the virus to those who have not? Without herd immunity, and until the answer is better known, masking to prevent spread will be necessary.
The vaccines being produced use a variety of vectors to protect the body from coronavirus, and have varying storage issues. The participants in their clinical trials were not identical: For example, the Pfizer vaccine is for people 16 and up; Moderna’s is for 18 and up. No vaccines trials have included pregnant women, and the CDC has said pregnant women wishing to take the vaccine should be informed that there is no data on whether it is safe for them. (Dr. Robert Hopkins, director of the Division of General Internal Medicine in the Department of Internal Medicine at the University of Arkansas for Medical Sciences and chair of the National Vaccine Advisory Committee, told the Times he would advise against vaccinating pregnant women.)
Like the flu vaccine, the COVID vaccines may not create total immunity to the disease but should lessen severity. It is not known how long they will confer immunity, or whether they will protect against variations of the virus as it mutates, as does the influenza virus. More about the vaccines and how they work:
The Pfizer vaccine: Genetic vaccine BNT162b2 requires two injections 21 days apart. It was shown to be 95% effective in clinical trials. Side effects reported (but not always occuring) included soreness and swelling at the site of injection, headache, nausea, fatigue, chills and fever. Since the vaccine rolled out, there have also been reports of allergic reactions, one serious.
Pfizer’s vaccine uses messenger RNA to prompt the body’s immune system. The mRNA encloses in a lipid nanosphere a bit of genetic material that prompts cells to make a particular part of the coronavirus: a spike protein. As the proteins rise to the cell surface — a process that takes about seven days — the immune system kicks in and makes antibodies. The mRNA does not introduce the virus’ complete genetic material, so cannot transmit COVID-19.
The vaccine, a powder, requires ultracool storage — -70 Celsius (-95 Fahrenheit) — to keep the genetic material from disintegrating. Shipping boxes contain GPS sensors to track the location and temperature of each box. The vaccine can be stored for up to six months in ultra-low-temperature freezers. When thawed (which takes about 30 minutes at room temperature), saline solution is added so it is injectable. Once the saline is added, it must be used within six hours. Each vial contains five doses, so five people should be ready to be immunized once the vial is thawed.
The Moderna vaccine: Moderna’s mRNA-1273 is also a genetic vaccine requiring two injections four weeks apart. It’s been shown to be 94.5% effective in clinical trials. Side effects include fever, chills, headaches, pain at injection site, fatigue, headache, muscle pain and joint pain, worse after the second injection.
The vaccine works in the same way as Pfizer’s, delivering a bit of the SARS-CoV-2 coronavirus in a lipid bubble to teach the body’s immune system to fight it off.
Storage of the Moderna vaccine is less complex than Pfizer’s: It can be stored at -20 Celsius (-4 Fahrenheit) for up to six months, refrigerated for up to 30 days and held at room temperature for up to 12 hours. A liquid, it does not require a diluent. Each vial contains 10 doses.
Johnson & Johnson’s vaccine, Ad26.COV2.S, uses an adenovirus engineered to transmit coronavirus genes, which is the system it used to create an Ebola vaccine. It requires only one injection, and can be kept in a refrigerator. The government has agreed to buy 100 million doses for $1 billion if the vaccine is approved. Efficacy is not yet known.
AstraZeneca’s vaccine, AZD1222, also uses an engineered adenovirus. In trials it’s been given in two injections four weeks apart; oddly, there was evidence that a half dose followed by a full dose was more effective than two full doses. The U.S. awarded the company $1.2 billion for 300 million doses.
The Novavax vaccine, NVX-CoV2373, uses protein antigens rather than genetic material. It requires two injections three weeks apart, and is stable in a refrigerator. Efficacy is not yet known. Novavax was awarded $1.6 billion for development and manufacturing.
The Sanofi-GSK vaccine uses viral proteins made from engineered viruses grown inside insect cells. Its agreement with the U.S. was $2.1 billion for 100 million doses. In phase 2 clinical trials, however, the company found the formulation produced antibodies better in people under 50 than those older, and plans to launch another phase 2 trial.
For the first few months of the pandemic, medicine had little to offer patients. Hydroxychloroquine, a malarial drug, was promoted by President Trump, and so Trump’s acolytes, including members of the Arkansas General Assembly, signed on. However, with the exception of a few crackpots, researchers found evidence that not only was the drug ineffective in the treatment of COVID, it was potentially dangerous to cardiac patients. In May, two months after Arkansas’s first hospitalization for COVID, the FDA authorized the emergency use of remdesivir, an antiviral that speeded up recovery for the seriously ill. It has now given remdesivir final approval. In June, a clinical trial in the U.K. found that the steroid dexamethasone could save the critically ill; it was authorized in the U.S. in July, and was given to Trump when he was hospitalized in October.
The latest treatments are monoclonal antibodies, produced in a laboratory to attack specific antigens and which have shown to lessen the severity of disease. Arkansas hospitals have been infusing eligible patients — people with mild to moderate cases of COVID who are at high risk of progressing to severe cases, including people with underlying health risks and people over 65 (or younger depending on their comorbidities) — since November. In December, HHS Secretary Alex Azar said people at risk of being hospitalized with COVID should “get on that product as soon as possible.” However, supplies of those drugs are limited as well: HHS allocated 3,360 doses of bamlanivimab and 914 doses of the Regeneron cocktail to be delivered to Arkansas by the end of the year. By mid-December, the state had received all but 12 doses of bamlanivimab.
Eli Lilly received $375 million and Regeneron $450 million from the government for the therapies.
There are numerous drugs being tested, both in clinical trials and in admitted patients, for the treatment of COVID-19 in Arkansas, including vaccines, antiviral agents, monoclonal antibodies and the like. In December, for example, Baptist Health’s Center for Clinical Research was running a Moderna vaccine trial and recruiting for trials of a preventative drug developed by AstraZeneca; UAMS was recruiting for a trial of the Johnson & Johnson vaccine. The Central Arkansas Veterans Healthcare System is trying the drug Degarelix to see if hormone suppression improves outcomes.
Sherian Kwanisai, nursing director for the health department’s Center for Public Health, was the first person in Arkansas to be vaccinated with the Pfizer vaccine, on Dec. 14. Four others were vaccinated with her (Pfizer vials include five doses), including members of the agency’s Healthcare Associated Infections team that worked with hospitals at the outbreak of COVID and Surgeon General Dr. Greg Bledsoe.
At UAMS, medical assistant Yolanda Emery, who works in the triage unit, volunteered to be first. “It was no different from a flu shot,” she said. Nurse Latasha McGown, a COVID survivor, was the first inoculated at Jefferson Regional Medical Center in Pine Bluff.
Romero called it a “historic day” and said it was important for “all of us when our time comes that we receive this vaccine” to achieve herd immunity and stop the virus. Until then, and until it’s known that the vaccine can not only protect the person vaccinated, but also prevent transmission from that person to others, he said, “We’re all going to be wearing these masks” and keeping our distance.
As the chairman of the Advisory Committee on Immunization Practices, Romero said, “It was a very emotional moment when we came to the unanimous decision to approve this vaccine.” He called it monumental, and as important as the development of the vaccine for polio, the scourge of the 1940s and ’50s.
He said he expected there to be enough vaccine for all in summer.