SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn

Authors:
Connors M, Graham BS, Lane HC, Fauci AS.
Citation:
SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn. Ann Intern Med 2021;Jan 19:[Epub ahead of print].

In this must-read article by Drs. Connors, Graham, Lane, and Fauci, the authors eloquently summarize the current state of coronavirus disease 2019 (COVID-19) vaccines, highlighting what is known and what is not and providing answers to the most frequently asked questions on the topic. The following are 10 key points to remember:

  1. The Pfizer-BioNTech and Moderna vaccines consist of synthetically produced messenger RNAs (mRNAs) that encode a stabilized form of the spike protein formulated in a lipid nanoparticle, which interim analyses of phase 3 trials showed approximately 95% protection against symptomatic disease.
  2. The AstraZeneca vaccine and Johnson & Johnson/Janssen vaccines use non-replicating adenoviral vectors (chimpanzee-derived adenovirus and human adenovirus, respectively) that contain DNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The AstraZeneca vaccine conferred 70% protection from clinical disease, albeit with variation between trials and dosing regimens. Efficacy data for the Johnson & Johnson vaccine are pending.
  3. Novavax is testing in phase 3 trials a vaccine consisting of recombinant spike protein produced in insect cells.
  4. The Pfizer-BioNTech and Moderna vaccines are the first and only vaccines to have received emergency use approval by the Food and Drug Administration (FDA) at the time of writing of this article.
  5. Phase 3 trials have so far excluded pregnant women, people <16 years old, and those with immunodeficiency or a history of allergic reactions to vaccines. Studies in pediatric populations are being planned.
  6. Overall, local and systemic reactions to vaccines are common, but mild. There was no difference in severe adverse events between placebo and vaccine groups.
  7. As large populations are vaccinated, it is possible for rare side effects to emerge. Inevitably, unrelated events that can occur any day in the absence of vaccines will occur around the time of vaccination. Attribution to the vaccines can only be done through careful epidemiologic analysis.
  8. The duration of protection afforded by the vaccines is unknown. One study showed a two-fold decline in antibody titers 3 months after the second dose of Moderna vaccine; similar to antibody declines seen with influenza vaccines.
  9. Whether vaccines protect against infection and transmission is unknown, and may have a dramatic impact on the pandemic given only 40-60% of Americans are planning to get vaccinated, according to recent polls.
  10. A lack of protection against infection may lead to false reassurance and persistent transmission from vaccinated to unvaccinated individuals as social distancing restrictions are relaxed. More data are needed to determine whether vaccines confer protection against infection and transmission.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Dyslipidemia, Prevention, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Lipid Metabolism

Keywords: Adenoviruses, Human, Adolescent, Anaphylaxis, Antibodies, COVID-19, Immunologic Deficiency Syndromes, Influenza Vaccines, Lipids, Nanoparticles, Primary Prevention, RNA, Messenger, Severe Acute Respiratory Syndrome, Spike Glycoprotein, Coronavirus, Vaccination


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