A light at the end of the COVID-19 tunnel

UPDATE:  The FDA issued the first emergency use authorization (EUA) for Pfizer-BioNTech’s COVID-19 Vaccine in individuals 16 and older on December 11, 2020. Vaccine distribution began December 13th. 

Image: Centers for Disease Control and Prevention/Lauren Bishop

 

Getting closer: Until now, only a small amount of data from the National Institute of Health(NIH)-Moderna and Pfizer-BioNTech trials data has been available. That will change this week

Distribution: Vaccines will not be shipped to hospitals, pharmacies, clinics or other administration sites until they have been authorized by FDA

Limited supplies: Since there won’t be enough vaccines for everyone who wants one at the start, they will only be given to people from priority groups at first.

Transparency builds Trust: People won’t take the vaccine unless they trust it’s safe. The government is working hard to win public trust through transparency

Side Effects: Although initial trial results indicate both vaccines are safe, more individuals are likely to have side effects temporarily preventing them from work or daily activity compared to the flu vaccine. Adults 65+ show milder symptoms.

Cost: The federal government is requiring COVID-19 vaccines to be free to whoever wants one, including the uninsured.

Credit: Centers for Disease Control and Prevention/Alissa Eckert, MSMI, Dan Higgins, MAMS

GETTING CLOSER: Until now, only a small part of the full vaccine trials data has been available. That will change this week. Initial clinical trial results for NIH-Moderna COVID-191 and Pfizer-BioNTech2 vaccines show they are highly (~95%) effective with no major serious side effects reported. These results came thanks to the over 45,000 participants who enrolled in the NIH-Moderna drug trial and the over 30,000 participants enrolled in the Pfizer-BioNTech vaccine trial. This week, the U.S. Food and Drug Administration (FDA) will be reviewing the full extent of clinical trial safety and effectiveness data, starting with Pfizer-BioNTech on December 10th. The FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC), a panel of independent scientific and health experts from around the nation, will discuss the data publicly with the public invited to join the discussion. VRBPAC will then make recommendations to the FDA about whether or not to approve Emergency Use Authorizations (EUA). EUA allows the use of an unapproved medical product, like a vaccine, if there is enough initial evidence that it is beneficial for society, and that its safety has been tested in clinical trials with large numbers of participants. EUA is basically a very highly educated guess, based on the scientific and medical evidence currently at hand, that the benefits of emergency authorization outweigh potential harms to the public.

DISTRIBUTION: Vaccines will not be shipped to hospitals, pharmacies, clinics or other administration sites until they have been authorized by FDA. Although the vaccines won’t be delivered to hospitals and other administration sites before EUA, they have begun being shipped to distribution sites for quicker delivery, in case authorization is given. The first shipments began near the end of November. States and territories are preparing to distribute the vaccines within 24 hours of EUA, according to officials from Operation Warp Speed (OWS), a public-private partnership between the government and companies to speed development and distribution of a COVID-19 vaccine. Review of trial information by VRBPAC will take about 4 days, so the first doses of Pfizer-BioNTech’s coronavirus vaccine are expected to be delivered around December 15th and NIH-Moderna around December 22nd.

The first doses of Pfizer-BioNTech’s coronavirus vaccine are expected to be delivered around December 15th and NIH-Moderna around December 22nd

LIMITED SUPPLIES: Since there won’t be enough vaccines for everyone who wants one at the start, they will only be given to people from priority groups at first. According to OWS Chief Operating Officer Mocef Slaoui, there will be about 40 million doses of vaccine available by the end of the year. Each person requires two shots, that’s enough for 20 million people This isn’t nearly enough for the 330 million people in the United States. Fortunately, the U.S. government has agreements in place with Moderna and Pfizer for 100 million doses of each vaccine with an option to purchase an additional 400 from Moderna and 500 from Pfizer. According to the Centers for Disease Control and Prevention (CDC), plans are in the works to make an additional 5-10 million doses of vaccine each week after EUA. This number will likely increase as other vaccines are approved. There are now over 60 potential COVID-19 vaccines being tested around the world.

To help determine who should get vaccinated first, the NIH and CDC asked the National Academies of Sciences, Engineering and Medicine (NASEM) to produce a study3 to help guide decisions on who gets priority vaccine access. On December 1st, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend that the first batch (phase 1a) of COVID-19 vaccines be provided to health care professionals and residents of long-term care facilities. The tentative phase 1b distribution, to be voted on at a later date, would include essential workers. Phase 1c would potentially include adults with high-risk medical conditions and adults over 65. States are not bound to follow federal prioritization so each state will decide who will be able to get a vaccine first. The highest priority group vaccinations will likely go to March. It won’t be long for the rest of us, however. The general public is expected to have access to the vaccine by around April to June according to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, in a recent interview on NBC’s Good Morning America. According to his estimates, we may be back to normal (whatever that means now) and filling stadiums by the end of summer. Maybe we’ll get to go to Burning Man or the Summer Olympics after all!

TRANSPARENCY BUILDS TRUST: People won’t take the vaccine unless they trust it’s safe. The government is working hard to win public trust through transparency. Given the quick speed of vaccine development, there are many people who have reservations about to get their COVID-19 shot. The government has been working to reduce fear and anxiety regarding vaccine safety. They have repeatedly emphasized that the EAU process, including all data for both COVID-19 vaccine clinical trials, will be public and open for public scrutiny and comment. Those watching VRBPAC’s December 10th and 17th meetings will be able to hear all discussions between VRBPAC and members of the FDA’s Center for Biologics Evaluation and Research (CBER). The public is invited to present data, information, or views, orally or in writing. One important thing to note is that VRBPAC members are not employed by the FDA or vaccine developers so they will, in theory, conduct a full and impartial review of the data presented without political or other pressure.

You may be asking yourself, and rightfully so, whether companies can be trusted not to fudge their trial data. There’s a lot of money at stake, after all. The FDA is way ahead of you. During both COVID-19 trials only an independent Data and Safety Monitoring Board (DSMB) was able to view and access clinical trial data and neither Pfizer nor Moderna were given information on who received the vaccine vs. placebo. The DSMB’s job has been to keep an eye on the trial and scientists to be sure the interest of participants and scientific honesty is protected and the top priority.

We may be back to normal and filling stadiums by the end of summer

Source: Wikimedia Commons

EFFECTIVENESS: The vaccines are highly effective, more so than the flu vaccine. The COVID-19 vaccines appear to be very effective in preventing COVID-19. Much more than the regular flu vaccines are at preventing the flu, in fact. Although the complete data for the Pfizer-BioNTech and NIH-Moderna phase 3 trials are not yet publicly available, a small glimpse of some of the data from each trial has been released. Results reported from the NIH-Moderna study indicate that their vaccine is 94% effective. This was from a review of 196 cases of COVID-19 in the over 30,000 participants from study. This group included 33 adults ages 65+, 42 from racial/ethnic minority groups and individuals with high risk of severe complications of COVID-19. Astonishingly, of the 196 COVID-19 cases observed, 185 were from the placebo group and 11 were from the vaccine group. 30 cases of severe COVID-19 were reported in the placebo (control) group, and none in the vaccine group. Those are some pretty amazing results. In comparison, the 2019-2020 flu vaccine4 for Influenza A and B is only 35-42% effective in adults according to the CDC. Initial analysis of Pfizer-BioNTech trial results indicates over 95% vaccine effectiveness. In Pfizer’s study of 170 cases of COVID-19 in their trial, 162 came from the placebo group while 8 came from the vaccinated group. Effectiveness was reported to be consistent across age, race and ethnicity, and gender demographics for both vaccines.

SIDE EFFECTS: Although initial trial results indicate both vaccines are safe, some individuals may have side effects temporarily preventing them from work or daily activity, more than the flu vaccine. Adults 65+ have milder symptoms. There were no major safety concerns reported for the over 75,000 trial participants vaccinated. The reported adverse events were described as temporary, going away in a few days for both vaccines. The table below compares what’s been reported so far for the two COVID-19 vaccines to one of this year’s flu vaccine, Fluarix Quadrivalent5. Note that the COVID-19 vaccines require a person to get two shots, staggered in time. The flu shot only requires one shot. As you can see, the initial results show significantly more people who were given COVID-19 vaccines experienced side effects that required pain medication or were temporarily debilitating. These are referred to as “Grade 3” side effects. Aside from injection site pain, the majority of Grade 3 side effects were seen after a person’s second COVID-19 shot. When compared to the flu shot: fatigue was 4-15x more likely, joint pain 10x more likely, headache 4-9x and muscle pain 2x more likely. People were also 3x more likely to experience Grade 3 pain after their first COVID-19 shot than for the flu. Side effects reported if they were seen in over 2% of people.

Results in the table below came from the review of a small (95) set of cases6 for the NIH-Moderna trial. Pfizer-BioNTech results came from an initial review of information from 8,000 participants. Since these are fairly small numbers of people compared to total people enrolled, it’s possible these numbers may change once all of the data is analyzed. Since much higher rates were seen in both vaccines however, we may in fact see higher rates of side effects with the COVID-19 vaccine.

Grade 3 reactions*NIH-ModernaPfizer-BioNTechFlu**
Fatigue9.7% (14x)3.8% (5x)0.7%
Joint pain5.2% (10x) 0.5%
Headache4.5% (9x)2.0% (4x)0.5%
Pain at injection site (1st  shot)2.7% (3x) 0.8%
Muscle pain8.9% (2x) 0.5%
Pain at injection site (2nd shot)4.1%  
Redness at injection site2.0%  
*Side effects reported in >2% of people. **Fluarix Quadrivalent. Source: https://gsksource.com. Numbers in parenthesis = How many times more likely than flu. Rounded to nearest 10th

Preparing workers for vaccine side effects: Given what we know so far, there have been warnings that the side effects shouldn’t be downplayed and there are initial reports of some vaccine recipients having to miss a day or two of work. In fact, the CDC recommends that vaccination programs for health care personnel consider these side-effects and stagger vaccinations for employees with similar functions or in the same units.

Side effects are milder for older people: Interestingly, side effects were reported to be milder in older patients. This is thought to be because immune systems become less responsive with age, and reactions to the shot are caused by the body’s immune system fighting against something it perceives as a threat, not the vaccine itself. It is important to note that the COVID-19 vaccines from either of the two companies do not contain the full virus itself, they only contain a code (mRNA) for a small piece of the virus and cannot cause infection from the virus. That code is read by our cells and translated into instructions for making a harmless protein that the body’s immune system mounts a response to. This primes the body should it encounter the actual SARS-CoV-2 virus

When compared to the flu shot: fatigue was 4-15x more likely

COST: The federal government is requiring COVID-19 vaccines to be free for whoever wants one, including the uninsured. Because the vaccines were purchased with taxpayer money, both vaccines will be free of charge to everyone. Health care providers will be prohibited from charging for administration of COVID-19 vaccines as a condition of receiving the vaccine free from the federal government. The Centers for Medicare and Medicaid Services (CMS) recently established that any COVID-19 vaccine that receives FDA authorization, including EUA, will be covered under Medicare at no cost to beneficiaries.  Provisions were also added to the CARES Act that covers COVID-19 vaccines by most private health insurance plans during this public health emergency without cost sharing from in-network or out-of-network providers. The federal government is working on reimbursing providers for vaccine administration. For uninsured individuals, providers will be reimbursed for administration of the COVID-19 vaccine through the Health Resources and Services Administration’s Provider Relief Fund.

Wishing you and your families health and safety during this pandemic. Let’s get through this, together.

 

My deepest gratitude to health care professionals

I want to express my deepest gratitude to health care professionals who have put their lives and the lives of their families on the line to help those in need during this pandemic. My family included. Our country owes you a debt of gratitude.


 

Disclaimer: I am a biomedical scientist by training, and am not an expert in vaccines, infectious diseases, epidemiology, or drug development. Information about COVID-19 is constantly evolving. For the most reliable and up-to-date information, please visit the CDC or FDA website.


 

References:

  1. Moderna Announces Primary Efficacy Analysis in Phase 3 COVE study for its COVID-19 vaccine candidate and filing today with U.S. FDA for Emergency Use Authorization. Moderna. 30 November, 2020. www.investors.modernatx.com/news-releases/news-release-details/moderna-announces-primary-efficacy-analysis-phase-3-cove-study
  2. Our COVID-19 vaccine study. What’s next? Pfizer. 20 November, 2020. www.pfizer.com/news/hot-topics/our_covid_19_vaccine_study_what_s_next
  3. A Framework for Equitable Allocation of Vaccine for the Novel Coronavirus. National Academies of Science, Engineering and Medicine. 2020. https://www.nationalacademies.org/our-work/a-framework-for-equitable-allocation-of-vaccine-for-the-novel-coronavirus
  4. US Flu VE Data for 2019-2020. Centers for Disease Control and Prevention. www.cdc.gov/flu/vaccines-work/2019-2020.html
  5. Fluarix Quadravalent (influenza vaccine) Highlights or Prescribing Information. GlaxoSmithKline. July 2020. www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Fluarix_Quadrivalent/pdf/FLUARIX-QUADRIVALENT.PDF
  6. Moderna’s COVID-19 Vaccine Candidate Meeting its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE study. Moderna. 16 November, 2020. https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy
  7. Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting all Primary Efficacy Endpoints. 18 November, 2020. Pfizer. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine

For information on participate in the upcoming FDA VRBPAC meeting, visit: www.fda.gov/advisory-committees/blood-vaccines-and-other-biologics/vaccines-and-related-biological-products-advisory-committee

For information on Operation Warp Speed, visit: www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html