Applied Evidence

COVID-19 vaccine insights: The news beyond the headlines

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Here is key intelligence on the recommended primary series, boosters, breakthrough infection, adverse events, special population vaccination, vaccine myths, and what the future might hold.


› Vaccinate all adults (≥ 18 years) against COVID-19, based on recommendations for the initial series and boosters. A

› Vaccinate patients against COVID-19 with evidence-based assurance that doing so reduces disease-related risk of hospitalization, myocardial infarction, stroke, need for mechanical ventilation, and death. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Worldwide and across many diseases, vaccines have been transformative in reducing mortality—an effect that has been sustained with vaccines that protect against COVID-19.1 Since the first cases of SARS-CoV-2 infection were reported in late 2019, the pace of scientific investigation into the virus and the disease—made possible by unprecedented funding, infrastructure, and public and private partnerships—has been explosive. The result? A vast body of clinical and laboratory evidence about the safety and effectiveness of SARS-CoV-2 vaccines, which quickly became widely available.2-4

In this article, we review the basic underlying virology of SARS-CoV-2; the biotechnological basis of vaccines against COVID-19 that are available in the United States; and recommendations on how to provide those vaccines to your patients. Additional guidance for your practice appears in a select online bibliography, “COVID-19 vaccination resources.”

COVID-19 vaccination resources

Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States

Centers for Disease Control and Prevention

COVID-19 ACIP vaccine recommendations

Advisory Committee on Immunization Practices (ACIP)

MMWR COVID-19 reports

Morbidity and Mortality Weekly Report

A literature hub for tracking up-to-date scientific information about the 2019 novel coronavirus

National Center for Biotechnology Information of the National Library of Medicine

Understanding COVID-19 vaccines

National Institutes of Health COVID-19 Research

How COVID-19 affects pregnancy

National Institutes of Health COVID-19 Research

SARS-CoV-2 virology

As the SARS-CoV-2 virus approaches the host cell, normal cell proteases on the surface membrane cause a change in the shape of the SARS-CoV-2 spike protein. That spike protein conformation change allows the virus to avoid detection by the host’s immune system because its receptor-binding site is effectively hidden until just before entry into the cell.5,6 This process is analogous to a so-called lock-and-key method of entry, in which the key (ie, spike protein conformation) is hidden by the virus until the moment it is needed, thereby minimizing exposure of viral contents to the cell. As the virus spreads through the population, it adapts to improve infectivity and transmissibility and to evade developing immunity.7

After the spike protein changes shape, it attaches to an angiotensin-converting enzyme 2 (ACE-2) receptor on the host cell, allowing the virus to enter that cell. ACE-2 receptors are located in numerous human tissues: nasopharynx, lung, gastrointestinal tract, heart, thymus, lymph nodes, bone marrow, brain, arterial and venous endothelial cells, and testes.5 The variety of tissues that contain ACE-2 receptors explains the many sites of infection and location of symptoms with which SARS-CoV-2 infection can manifest, in addition to the respiratory system.

Basic mRNA vaccine immunology

Although messenger RNA (mRNA) vaccines seem novel, they have been in development for more than 30 years.8

mRNA encodes the protein for the antigen of interest and is delivered to the host muscle tissue. There, mRNA is translated into the antigen, which stimulates an immune response. Host enzymes then rapidly degrade the mRNA in the vaccine, and it is quickly eliminated from the host.

mRNA vaccines are attractive vaccine candidates, particularly in their application to emerging infectious diseases, for several reasons:

  • They are nonreplicating.
  • They do not integrate into the host genome.
  • They are highly effective.
  • They can produce antibody and cellular immunity.
  • They can be produced (and modified) quickly on a large scale without having to grow the virus in eggs.

Continue to: Vaccines against SARS-CoV-2


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