With an efficacy rate of 95%, the Pfizer/Biontech COVID-19 vaccine received Emergency Use Authorization (EUA) for patients older than age 16 from the US Food and Drug Administration (FDA) on December 11, 2020 (EUA is not FDA approval). With a collective sigh of relief, the world greeted the news. Finally, there is a light at the end of the tunnel.

The Pfizer/Biontech vaccine contains a nucleoside-modified messenger RNA encoding the viral spike glycoprotein (S) of SARS-CoV-2 formulated in lipid nanoparticles. The mRNA allows expression of the SARS-CoV-2 S antigen. The phase 2/3 study evaluated almost 44,000 patients with 43,448 participants over age 16, and 37,586 followed for a median of 2 months for safety. The study found that 2 0.3 mL intramuscular vaccine injections dosed 3 weeks apart was 95% effective (95% CI, 90.3-97.6). In the phase 2/3 study, adverse events (AEs) included pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and fever (14.2%).¹ A lot has been made in the mainstream media of this AE rate. However, in the placebo control group, AEs also included fatigue (33.4%), headache (33.7%), muscle pain (10.8%), chills (6.4%), and joint pain (6%), possibly due to the placebo effect. Serious AEs were similar between groups. To all of us, I am sure these rates are acceptable, but we must evaluate the risks and benefits before administering.

Moderna’s mRNA-1273 is a lipid nanoparticle-encapsulated, nucleoside-modified, mRNA-based vaccine that encodes the S-2P antigen stabilized in its prefusion conformation, consisting of the SARS-CoV-2 glycoprotein with a transmembrane anchor and an intact S1/S2 cleavage site of the full-length SARS-CoV-2 spike protein. It was developed in the Operation Warp Speed vaccine accelerator, receiving almost $1B in funding. Like the Pfizer vaccine, it requires 2 doses of 100 µg of mRNA-1273, but they are delivered 4 weeks apart as opposed to Pfizer’s 3. Moderna’s phase 2/3 COVE study enrolled more than 30,000 patients in the United States and reported an efficacy rate of 94.1%, with 100% effectiveness against severe COVID-19. The safety of the vaccine was reported differently than Pfizer’s, with Grade 3 (severe) events after the first dose including injection site pain (2.7%), and Grade 3 events after the second dose including fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%), and erythema/redness at the injection site (2.0%).² The FDA granted EUA to Moderna for mRNA-1273 on December 18, 2020, for individuals age 18 and older.

Informal polling of my friends reveals that almost all of my health-care peers intend to receive the vaccine immediately. Not so much with my other friends; for them, the AE rate is a big issue. And, of course, questions remain. However, it is exciting that we are almost waking from this nightmare of a year. Stay safe, my friends! RP

REFERENCES

1. US Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine EUA fact sheet for healthcare providers. December 2020. https://www.fda.gov/media/144413/download
2. US Food and Drug Administration. FDA briefing document Moderna COVID-19 vaccine. Decembber 17, 2020. https://www.fda.gov/media/144434/download