The Pfizer/BioNTech and Moderna COVID-19 vaccines – BNT162b2 and mRNA-1273, respectively - will likely be approved under Emergency Use Authorization (EUA) in the days following the FDA meeting scheduled for December 8th to the 10th.
Here is what you need to know going forward.
Is the COVID-19 vaccine safe?
Based on the available data, the front-runner COVID-19 vaccines appear to be safe; however, the meaning of “safe” depends the situation and the meanings of “side effect” and “Grade 3 adverse drug reaction,” which can have subtle but meaningful variations. The percentages of adverse reactions have been in the low single digits across tens of thousands of patients, and that’s welcome news.
Pfizer stated that the "only Grade 3 (severe) solicited adverse events greater than or equal to 2% in frequency after the first or second dose were fatigue at 3.8% and headache at 2.0% following dose 2." The definition of a grade 3 adverse drug reaction is "medically significant but not immediately life threatening." 2% may sound low, but that would be 2 million headaches for every 100 million vaccinations. We will know a lot more about undetectable adverse events as the high-risk population is vaccinated in 1Q21.
Is storing and transporting the vaccine going to be a problem?
Moderna’s vaccine can be stored in a refrigerator (not difficult) and shipped at a more manageable -20C, while Pfizer’s vaccine requires extreme handling at -70C (relatively more difficult but not impossible). The shipping container Pfizer will use is a cardboard box lined with Styrofoam and packed with dry ice, and dry ice appears easy to make and reasonably plentiful. Once the vaccines are thawed and refrigerated, Moderna says its is stable for up to a month in a refrigerator, while Pfizer/BioNTech’s is “good” for up to 5 days.
When will the COVID vaccine be available for people at high risk?
The vaccine will be available only to people at high risk (71 million) when the FDA grants an EUA in the days following the FDA Advisory Panel Meeting scheduled for December 8 to 10.
Who will be given the vaccine first?
The FDA’s EUA will likely call for the vaccination of front-line Healthcare workers and at-risk populations, such as those with serious medical conditions, or people over the age of 65. There are ~16 million Healthcare workers in the United States, ~5 million people under the age of 65 and categorized as Poor Health status, and ~50 million people over the age of 65 (thus the total of ~71 million people potentially defined as high risk under the EUA). The COVID-19 case fatality rate ranges from 5.0% to 25.0% for people over 65 years old, while for the low risk population, the case fatality rate is below 1.0%. The risk-reward balance is clear for who should/will be vaccinated first. Reports of the reluctance in getting vaccinated among low risk populations look rational but are also somewhat irrelevant.
When will the COVID vaccine be available to a general population?
Full approval of the COVID vaccine for a general population will follow a Biologics License Application (BLA) submission to the FDA. Pfizer suggested approval for a general population will come “several months” after the EUA, while others such as Scott Gottleib, the former head of the FDA, have publicly suggested availability in mid-2021. By the time the general population receives the COVID-19 vaccine, we think the hospitalization and death rates will have dropped considerably.
How will the vaccine be distributed?
There is an important Centers for Disease Control (CDC) meeting today (11/23) to discuss distribution (allocation) of the vaccine(s). This is probably the most important thing to pay attention to because a slow roll out won’t be effective.
How is the mRNA vaccine manufactured and can they make enough vaccine for everybody?
Polymerase chain reaction (PCR) is a process that can make a great deal of genetic material very quickly. For each cycle of the PCR reaction, which takes a minute or two, the genetic material doubles, so one can have a lot of material very quickly. A single vaccine dose is 100 micrograms, which means we need to produce vaccines on the order of several kilograms, which seems reasonable.
How long will the vaccine protect me?
There is not yet a good answer to how long someone maintains immunity after contracting COVID-19 or receiving a vaccine. There have been reports of COVID19 patients being re-infected and other studies showing falling antibody levels in patients who have had COVID. It will take more time and more data to figure this out. One solution may be to give at risk patients a booster shot depending on how the pandemic evolves over the next few years.
What does it mean that Moderna and Pfizer executives sold stock?
Executives will often have prearranged stock sales on the calendar for financial planning purposes. It was concerning to see executives selling stock around the time that vaccine data was scheduled to be announced, but the data release was positive with no concerning red flags. While these insider sales were poorly timed, with positive data in hand after the fact, the sales appear only to be tone deaf.
Will the COVID vaccine be combined with seasonal flu vaccine?
We have not seen any requirement for additional safety data for patients receiving both a flu vaccine and a COVID vaccine. There are mRNA-based influenza vaccines currently in clinical trials. At some point it seems likely that the two are combined into a single shot.
Will people be able to choose which vaccine they receive?
It should not be difficult to ask a few questions to find out which vaccine is in the syringe. As long as you’re comfortable with a little effort and some social discomfort, you can probably get the brand of COVID vaccine you want.
When will things get back to normal?
While 95% efficacy sounds like COVID will soon be over, getting back to normal is more complicated than it would seem. Normal means that the hospital system is not at risk of being overwhelmed. If a high percentage of the at-risk population is vaccinated, then hospitalization rates will decline rapidly, and the public health restrictions will moderate. However, if the vaccination program is slow and COVID cases are rising rapidly, case growth will outpace vaccinations and any improvement in hospitalization rates will be slow. A slow vaccination program combined with rapid COVID infection rates could even overwhelm a vaccine with even 100% efficacy. Expect to be wearing a mask well into 2021.
The logistics for vaccine deployment looks complicated, can we pull this off?
If we only needed to vaccinate healthcare workers and nursing home or assisted living facility residents, it would easy to distribute the vaccine, but only 1.5 million people live in nursing homes, and 1.0 million people live in assisted living. The COVID-19 vaccination program will have to involve community outreach. On the positive side, high risk people see their doctor and visit a pharmacy regularly, so they should be easy to find.
How long will it take to vaccinate everyone?
The pace of vaccination depends on how many people are hired and how smoothly the operation runs. Assuming one person can vaccinate one patient every five minutes over an 8-hour shift, that would yield 96 vaccinations per shift. For every person delivering vaccinations, you might need 3 to 6 support staff. With 2 shifts of 8 hours, a team of 6-10 people might vaccinate ~200 people per day. If the goal is to deliver 1.0 million vaccinations a day, a pace that would reach 71 million at risk people over 10 weeks, it would require a staff of 30,000 to 50,000.
Should COVID-19 vaccine be mandatory?
Since social distancing is a reasonably effective strategy to prevent COVID-19 infection and the vaccine is new, it is unlikely that anyone is going to be forced to be vaccinated, at least under the EUA and in the early phases deployment. Assuming the safety data stacks up over the coming weeks and months and is included in the BLA, requiring a COVID vaccine may become more common over time. It is easy to imagine something short of forced vaccinations such as employers requiring proof of vaccination to return to in-person work situations. Many hospitals require employees to get a flu vaccine, but flu vaccines have decades of safety data, and nobody flinches. COVID-19 vaccine and a novel vaccine platform for a novel disease and we expect more than few people hesitate.
What are the best COVID-19 vaccine stocks?
Both $PFE and $MRNA will be first to launch a COVID-19 vaccine and well into grabbing much of the available market among the high-risk populations defined under the EUA in the next few weeks. The long side is likely played out for these two names unless there is significant clinical news that extends the mRNA vaccines to new treatment areas other than COVID-19. Pharmacies like $CVS, $WBA, and $RAD will play a significant role in the shorter term, but the younger low risk population is reluctant to get a COVID-19 vaccine, possibly leading to disappointment in 2H21 – i.e., it seems likely COVID-19 vaccinations will be short lived boost to revenue. $ONEM will likely be less exposed to vaccinating high-risk patients than $WMT and $OSH in the initial roll out, but the demand among younger, urban, and high income workers is likely to increase over time and remain a tailwind throughout 2021. Also, $AMN is likely to continue to benefit as staffing demand remains high due to nurse fatigue and other staffing needs. The real opportunity is to look past the headlines and consider a durable return to in-person care and a big increase high acuity cases that has been building up throughout 2020. Stay tuned!