January 2021: Current State of the Pandemic, mRNA Vaccines, and Bottlenecks
By Edward Chen
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Coming into 2021, the coronavirus pandemic remains a significant problem. So far, COVID-19 has caused over 400,000 deaths in the US and 2.1 million deaths have been reported to the World Health Organization. According to the US Census Bureau, the US population is around 330 million people. This means that over 1 in 1,000 Americans have died from COVID-19. According to data from the US Centers for Disease Control and Prevention, or CDC, the US surpassed this tragic milestone a day after Christmas on December 26 last year. Today, 1.25 in 1,000 Americans have died from COVID-19. This is the equivalent of 125 deaths for every 100,000 people. The CDC forecasts that deaths will continue to rise and that by February 15, the US will reach around 490,000 total deaths from the coronavirus.
Focusing on the current month, the CDC reported 4,383 deaths just 5 days ago on January 20, 2021. This marked the second worst day on record in terms of deaths and the worst day since April 15, 2020, shortly after the coronavirus first appeared in the US. In terms of cases, and in line with a recent 2 week trend of a decrease in new cases, the CDC recorded 170,000 new cases on January 23. This is down from an all-time high of slightly over 314,000 new cases on January 8, which reflected an increase in cases as a result of the holiday season.
Fortunately, scientists have been studying the coronavirus and working on vaccine development. The US Food and Drug Administration, or FDA, has now authorized two COVID-19 vaccines for emergency use. The first, the Pfizer-BioNTech COVID-19 vaccine, was granted an emergency use authorization by the FDA on December 11, 2020. This was followed by the FDA issuance of an emergency use authorization for the second vaccine, the Moderna COVID-19 vaccine, a week later on December 18, 2020.
These actions allow vaccines for the prevention of COVID-19 to be widely distributed across the US, though the specific timelines will differ across states. For example, Massachusetts expects to make the coronavirus vaccine available to the general public starting in April. Three other COVID-19 vaccines, from AstraZeneca, Johnson & Johnson, and Novavax, are currently in large-scale Phase 3 clinical trials in the US.
However, even after vaccine development and approval, challenges remain with supply and distribution.
The two COVID-19 vaccines currently approved in the US are mRNA vaccines. This means that these vaccines contain within them messenger RNA, or mRNA. mRNAs are a class of molecules that serve as molecular instructions for cells to make proteins. The mRNA in the COVID vaccine—coated by a lipid membrane for its efficient delivery into cells—codes for noninfectious coronavirus proteins that will be made by muscle cells after vaccine injection.
When our immune cells are exposed to and recognize these noninfectious viral particles beforehand, they will make antibodies that can bind to and mark these viral proteins for destruction. Because these proteins are identical to parts of the coronavirus, the resulting antibodies created by the immune response will attack the real, infectious coronavirus too.
In addition, pre-exposure to these noninfectious viral particles allows our immune system to not only generate antibodies, but to generate antibodies that are more specific against the virus, therefore allowing our antibodies to better target the coronavirus. This prepares our bodies for a potential exposure to the real, infectious coronavirus.
A downside to the approach of mRNA vaccines is that mRNA is inherently unstable. This necessitates that the mRNA vaccines remain cooled at very low temperatures from the factory all the way to vaccine distribution centers. Any challenges with distribution are compounded by the fact that both the Pfizer-BioNTech and the Moderna COVID-19 vaccines require two doses for full efficacy.
In the case of the Pfizer-BioNTech COVID-19 vaccine, the vaccine must be kept in ultra-low temperature freezers at temperatures of -80 °C to -60 °C (or -112 °F to -76 °F) until shortly before use. This is the temperature range the vaccine is shipped at. Once at its destination, the Pfizer-BioNTech vaccine can also be stored at higher temperatures of 2 °C to 8 °C (36 °F to 46 °F) in a refrigerator for up to 5 days before the vaccine must be discarded.
The Moderna COVID-19 vaccine uses different materials for the lipid membrane and therefore can be shipped and kept at a higher temperature of between -25 °C to -15 °C (or -13 °F to 5 °F). The Moderna vaccine can also be stored at the same milder temperature range of 2 °C to 8 °C (36 °F to 46 °F) at its destination, but for a longer period of up to 30 days. Most vaccines, such as all influenza vaccines (see footnote) and both 2009 H1N1 vaccines, are stored at this milder temperature range that requires only a refrigerator.
The need to maintain the Pfizer-BioNTech and Moderna COVID vaccines at low temperatures throughout the entire shipping process unsurprisingly creates a challenge that needs to be solved. This is a recognized problem—and engineers are already creating solutions.
Pfizer has manufactured purpose-built containers to ship their coronavirus vaccines. Dry ice has a surface temperature of -78.5°C (or -109.3 °F). This is conveniently in the low temperature range required by the Pfizer-BioNTech vaccine and is utilized by Pfizer for shipping their vaccines. This does not present significant additional challenges as shipping items packed with dry ice is an already common process and procedures have already been developed for this purpose. Pfizer states that their containers can store the vaccine for up to 30 days, as long as dry ice is replenished every five days. The distribution process includes the delivery of “Dry Ice Recharge Kits.” This allows the Pfizer-BioNTech vaccines to be stored in Pfizer’s containers at vaccine distribution centers for up to 30 days before an ultra-low temperature freezer is needed.
Moderna vaccines, which require less extreme temperatures, are shipped in cooled, insulated containers with a temperature monitor by a separate distribution company. This distribution company, McKesson, was already awarded a contract by the CDC in 2016 to, if necessary, deliver vaccines at temperatures of -20 °C and/or between 2 °C to 8 °C during the event of a pandemic. McKesson also distributed H1N1 vaccines during the 2009 H1N1 pandemic. Both McKesson and Pfizer ultimately ship the vaccines they process through UPS and FedEx, which means that UPS and FedEx collectively handle all coronavirus vaccine shipments in the US.
To date, over 41.4 million vaccine doses have been shipped by the federal government to US states, territories, and other government entities such as the Department of Defense. Of the vaccine doses distributed, about half have been administered. 21.8 million COVID-19 vaccine doses have now been administered to a total of 18.5 million people, with 3.2 million people now vaccinated with the full 2 doses.
Production, rather than distribution, may actually be a more significant bottleneck. The Pfizer vaccine is currently approved for people 16 or older while the Moderna vaccine is approved for people 18 or older. To vaccinate every American 18 or older requires over 510 million vaccine doses for some 255 million people.
When the goal shifts from vaccinating everybody to vaccinating enough people to achieve herd immunity, the number of doses needed drops to somewhere between 380 and 460 million doses. This assumes that herd immunity is achieved by vaccinating somewhere between 75 to 90 percent of the population, a figure often given by Dr. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases. To put the figure of 380 to 460 million doses in perspective, the US government has an agreement with Moderna to purchase 200 million doses to be delivered by June 30 and a separate agreement with Pfizer to purchase 100 million doses to be delivered by July 31.
Ultimately though, despite all the challenges we face, the pressing need for coronavirus vaccines has advanced science. For example, Moderna, which specializes in mRNA therapies and was founded 10 years ago, had not released any products until its COVID-19 vaccine last year. The experience gained from developing a COVID-19 mRNA vaccine opens the path to future mRNA vaccines, such as immunizations similar to a chikungunya virus vaccine Moderna had already been developing before the pandemic. No vaccines are currently approved for the prevention of chikungunya virus infection.
Challenges are very real, but so are advances.
The FDA lists 10 different influenza vaccines that have been released for the 2020-2021 flu season: Afluria Quadrivalent, Fluad, Fluad Quadrivalent, Fluarix Quadrivalent, Flublok Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent, FluMist Quadrivalent, Fluzone High Dose Quadrivalent, and Fluzone Quadrivalent. Based on section 16 in the package inserts (linked in the previous sentence), each one is to be stored refrigerated between 2 °C to 8 °C (or 36 °F to 46 °F).
Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on January 25, 2021.
Edward Chen is a master's student studying immunology. He's also the national president of Students vs. Pandemics. @EdwrdChen