There has been very good news reported recently from ongoing Phase 3 COVID-19 vaccine trials. Two so–called mRNA vaccines COVID-19 vaccines have shown very high efficacies including one produced by Pfizer and another by Moderna. Pfizer reported an efficacy of 94.5% and Moderna 95%. Efficacy is measured by calculating the risk of a disease among vaccinated and unvaccinated persons and determining the percentage reduction in risk of disease among vaccinated persons relative to unvaccinated persons. This means that with these vaccines, 95% fewer people will have symptomatic disease. It is extremely promising that the efficacies of these vaccines are so high. Pfizer and Moderna have each asked for Emergency Use Authorization (EUA) from the United States Food and Drug Administration (FDA) and approval could be given within days. Once the FDA has authorized the vaccines they will be distributed and administered throughout the U.S. and globally.
The Pfizer vaccine is administered via intramuscular injection in two doses three weeks apart resulting in 94.5% efficacy including 94% in older adults, which is especially good news because severe COVID-19 disease rates increase with age. There was only one case of severe disease in the vaccine group in early trial results which suggests that it is highly protective against severe disease in all age groups. The Moderna vaccine is administered through intramuscular injection in two doses four weeks apart resulting in 95% efficacy in all ages and racial groups against symptomatic disease and none of the 15,000 trial participants who received the vaccine became severely ill, which is a remarkable result. Both companies also reported that there were no severe side effects from the vaccines, thus the initial indication is that the vaccines are very safe. The FDA requires at least two months of safety data for an EUA. The trial results reported by the two companies are very encouraging; however, they have not yet released the full details of the trial results. The FDA will have access to all trial data for EUA consideration and thus if they are approved then the FDA will have deemed the vaccines not only efficacious but also safe.
Distributing these vaccines will be a herculean task. If the Pfizer and Moderna vaccines receive FDA approval, then the first vaccine shipments of the Pfizer vaccine could be as soon as mid–December and Moderna soon after. Pfizer has reported they expect to produce about 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021. The number of people who can be vaccinated is half those numbers, simply because each person will need two doses. The U.S. government placed an initial order of 100 million doses of the Pfizer vaccine and may order up to 500 million additional doses. Moderna has reported that they expect to produce approximately 20 million doses for the U.S. market by the end of 2020 and eventually a billion doses globally. One drawback of the Pfizer vaccine is that it needs to be stored at extremely cold temperatures, at minus 70 degrees Celsius. The Moderna vaccine also needs to be frozen but only at minus 20 Celsius, a temperature similar to a normal freezer. This makes logistics of the vaccine distribution difficult. Distribution does not only involve physical logistics but also a determination of who will get the vaccine first because it will be in limited supply initially. In the U.S., the Advisory Committee on Immunization Practices convened by the Centers for Disease Control and Prevention (CDC) is making recommendations. When you are able to receive a vaccine will depend on your job, your age, and whether you have preexisting conditions. Since vaccination programs are implemented by state health departments there will be differences in the timing of who receives COVID-19 vaccines in different states. The CDC has estimated that if both the Pfizer and Moderna vaccines receive EUA then there will likely be enough doses for 20 million people by the end of 2020 and those numbers will increase substantially in the first half of 2021. The CDC Committee has already recommended that frontline healthcare workers and elderly residents of long–term care facilities be vaccinated first. Health-care workers will include nurses and likely nursing students as well as staff of nursing homes and other long–term-care facilities. Next in line will likely be other first responders followed by older people and people with pre–existing conditions that would increase their risk of severe disease. Other essential workers such as teachers are also likely to get access to the vaccines earlier. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, recently estimated that people without underlying conditions in the “general population” would have access to the Pfizer and Moderna vaccines sometime between April and July 2021.
While the availability and distribution of the vaccines present difficult challenges, vaccine hesitancy and refusal could be a major barrier to getting a large percentage of the population vaccinated. A recent Associated Press–National Opinion Research Center poll found that only about half of people said they would be willing to get a COVID-19 vaccine, about 30% said they were unsure, and 20% said they would be unwilling to get vaccinated. Health care workers and students are required to be vaccinated against various diseases, and organizations collect data that ensures compliance. Health care workers will almost surely be required to be vaccinated against COVID-19 once the vaccines are available and thus tools that ensure compliance will be essential. In the future, there might also be mandatory COVID-19 vaccination beyond healthcare settings. For example, vaccination might be compulsory for students in particular educational institutions or workers in particular organizations, and tools that facilitate compliance will be essential.
There is still much we do not know about the Pfizer and Moderna vaccines. We do not know how long the efficacy will last and when after vaccination effectiveness will begin to wane. We also do not know whether being vaccinated will stop person–to–person transmission. At present we know the vaccines are effective at preventing symptoms and severe disease in healthy adults. If the vaccines do prevent transmission, then vaccinating a large proportion of the population could potentially end the pandemic. In the meantime, it is important that people continue with public health approaches that limit transmission including wearing masks and physical distancing. These preventive measures should be used even for people who have been vaccinated at least until we know whether the vaccines stop transmission. Also, these vaccines have only been tested in healthy adult populations and as trials move forward children will be included. Pfizer recently added trial participants as young as 12 years old. The vaccines have also not been tested in pregnant women yet. There is still much we need to learn in order to protect our entire population.
COVID-19 is a global pandemic and the virus does not respect borders. Thus, it is in the interest of all countries that not only their own populations are vaccinated but that a large proportion of the the world’s population is vaccinated. Most developing countries do not have the capacity to distribute and administer a vaccine that needs to be stored at very cold temperatures. As mentioned above, mRNA vaccines such as those produced by Pfizer and Moderna require these cold temperatures, but other types of vaccines do not. For example, adenovirus-based vaccines are much easier to manufacture than mRNA viruses and thus much cheaper and they can be stored in standard refrigerators for at least six months. One COVID-19 adenovirus–based vaccine in a Phase 3 trial was developed by the University of Oxford and AstraZeneca. Initial trial results were recently reported, and a full two-dose combination had an efficacy of 62%, however surprisingly when the first dose was at half strength, the efficacy was 90%. A continuation of the trial is necessary to determine the efficacy at different dosages. There are also other adenovirus-based vaccines that are presently in trials including one produced by Johnson & Johnson. In addition, globally there are more than 150 COVID-19 vaccines developed using many different technologies in different stages of trials that are presently being tested. Ultimately when a low–cost vaccine is produced that can be distributed easily to the entire world then we can hopefully see the end of the COVID-19 pandemic.
Data will be key to evaluating the efficacy of these vaccines within widespread public distribution in the U.S. As such, the need to track and document vaccinations (in addition to storing the vaccines themselves) in a manner that’s safe, secure, and compliant with federal and state rules and regulations will be of the utmost importance.