Update on COVID-19 Vaccination

(A version of this article was published in the March 2025 issue of Public Citizen’s Health Letter.)

As one of his last actions as Food and Drug Administration (FDA) commissioner, Robert Califf, M.D., posted an essay about his “personal reflection” on COVID-19 vaccines, concluding in bold text:[1]

The question for the individual is: “If I take the vaccine, will I be more likely to be alive, free of serious illness, hospitalization, and long COVID than if I do not?” Based on our most current knowledge, I believe the answer is clearly “yes.”

Califf’s favorable conclusion about COVID-19 vaccination is consistent with those of authoritative clinicians (UpToDate authors)[2] and the Advisory Committee on Immunization Practices (ACIP), convened by the Centers for Disease Control and Prevention (CDC).[3],[4]

UpToDate authors and the ACIP/CDC recommend that all persons over 6 months of age be vaccinated or boosted with COVID-19 vaccines to guard against illness and death from circulating strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. For persons who are aged 65 or older or are immunocompromised, a booster dose is recommended six months after the prior dose. A previous, severe allergic reaction, such as anaphylaxis, is a contraindication. Nonetheless, as of Feb. 8, 2025, CDC data showed that only 23% of adults and 12% of children have received a 2024-2025 version of the COVID-19 vaccine.[5]

The system to authorize and recommend vaccines

Two federal agencies and two federal advisory committees are essential for evaluating vaccines and developing recommendations for their use. The agencies are the FDA and the CDC. The committees are the FDA’s Vaccines and Related Biological Products Advisory Committee and the CDC’s ACIP, which makes recommendations to the CDC’s director about how vaccines should be used.

COVID-19 vaccine development

Operation Warp Speed, implemented by the first Trump administration, launched the rapid development of COVID-19 vaccinations.[6] Messenger ribonucleic acid (mRNA) technology was key to that effort. In 2025 two mRNA vaccines by Moderna (SPIKEVAX)[7] and Pfizer (COMIRNATY)[8] are the only FDA-approved COVID-19 vaccines. A recombinant protein-based COVID-19 vaccine (NOVAVAX) is available under FDA emergency use authorization for individuals 12 years of age or older.[9]

The mRNA vaccine manufacturing platform enables COVID-19 vaccines to be efficiently updated to reflect changes in the strains of the virus that are most important to protect against.[10]

Clinical outcome data

The “overwhelming benefit” of the mRNA vaccines was observed in the initial clinical trials.[11] A 2022 Cochrane review of COVID-19 vaccine randomized clinical trials concluded that, compared with placebo, most vaccines “reduce, or likely reduce,” symptomatic COVID-19 or severe and critical COVID-19.[12] For example, a trial including over 46,000 individuals who were at least 16 years of age found the Pfizer vaccine to be over 95% effective (severe COVID-19 case rates of 4 [with vaccine] versus 100 [with placebo] per 100,000). That Cochrane analysis further concluded there was “probably little or no difference between most COVID-19 vaccines and placebo for serious adverse events.”

Because the benefits of COVID-19 vaccination decline within months, the CDC recommends boosters, with the frequency based on the age of the recipient and whether they have certain chronic conditions or a weakened immune system. Updated immunizations, booster doses or new mRNA formulations can also address emerging strains of the mutating COVID-19 virus.[13]

For the most recent COVID-19 vaccination recommendations (2024-2025), ACIP/CDC reviewed available data on COVID-19 strains and recent observational studies about the effects of existing COVID-19 vaccinations.[14] Overall effectiveness for the 2023-2024 vaccines against COVID-19 infections serious enough to require a visit to urgent care or an emergency department, which are known as “medically attended” visits, was estimated at 43%; the vaccines reduced the risk of hospitalization by 44% and death by 23%.

These results came from a combined review of 16 studies that included thousands of vaccinated and unvaccinated individuals. For example, one study observed that 7.5% (1,297 of 17,229) of vaccinated individuals experienced medically attended COVID-19 compared with 11.9% (13,378 of 111,596) of unvaccinated individuals, yielding a statistically adjusted vaccine effectiveness of 47% on a population basis.

Another general population study observed hospitalization rates among vaccinated individuals of 198 per million (253 of 1,279,802) and among unvaccinated individuals of 389 per million (1,955 of 5,026,509), corresponding to statistically adjusted effectiveness of 40%. Death rates observed in another study were 62 per million and 157 per million, respectively.

In infants and children, a single study involving over 30,000 individuals showed that the vaccine was 80% effective at preventing medically attended COVID-19 visits.[15]

For serious adverse events, ACIP analyses focused on three previously identified concerns: anaphylaxis (severe allergic reaction) and myocarditis or pericarditis (inflammation around the heart). Anaphylaxis was observed within a day of vaccination in about five people per million.

Heart inflammation was more common, especially in 16- and 17-year-old males, who experienced nine such adverse events among 47,874 receiving a vaccine. The ACIP further found that men aged 18-29 years experienced seven heart inflammation events out of 166,973 men given the vaccine. Accordingly, although the acute heart inflammation risk in adolescent and young-adult men appears elevated compared with other subgroups, it continues be a very small risk of the COVID-19 mRNA vaccines.[16]

Special considerations

As Califf noted in his essay, there has been “intense debate” about the immunization of relatively low-risk individuals.[17] Individuals at low risk of severe COVID-19 infections include otherwise healthy children, adolescents, pregnant persons, and persons who have previously been infected by the virus.

Evidence suggests, however, that the benefits of COVID-19 vaccination outweigh the risks even for these low-risk groups.[18] Moreover, although prior infections confer some future immunity, repeat infections often occur, and their cumulative effects may include long COVID. Long COVID is a condition that emerges after acute COVID-19 infection has seemingly resolved, resulting in chronic illness (of at least three months).

What You Can Do

Work with your pharmacist or clinician to receive at least one 2024-2025 mRNA vaccine for COVID-19. Persons who are moderately to severely immunocompromised and those over 65 years of age are especially encouraged to be fully vaccinated and regularly receive booster vaccinations.

References

[1] Califf RM. Vaccines for COVID-19: A personal reflection. January 13, 2025. https://www.fda.gov/news-events/fda-voices/vaccines-covid-19-personal-reflection. Accessed February 3, 2025.

[2] Edwards KM, Orenstein WA. COVID-19: vaccines. UpToDate. January 23, 2025.

[3] Panagiotakopoulos L, Moulia DL, Godfrey M, et al. Use of COVID-19 vaccines for persons aged ≥6 Months: recommendations of the Advisory Committee on Immunization Practices — United States, 2024–2025. MMWR Morb Mortal Wkly Rep 2024;73:819–824.

[4] Roper LE, Godfrey M, Link-Gelles R, et al. Use of additional doses of 2024–2025 COVID-19 vaccine for adults aged ≥65 years and persons aged ≥6 months with moderate or severe immunocompromise: recommendations of the Advisory Committee on Immunization Practices — United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:1118–1123.

[5] Centers for Disease Control and Prevention. COVIDVaxView. February 19, 2025. https://www.cdc.gov/covidvaxview/weekly-dashboard/index.html. Accessed February 20, 2025.

[6] Califf RM. Vaccines for COVID-19: A personal reflection. January 13, 2025. https://www.fda.gov/news-events/fda-voices/vaccines-covid-19-personal-reflection. Accessed February 5, 2025.

[7] Moderna Label: COVID-19 vaccine, mRNA (SPIKEVAX). September 2024. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f96b315c-fa57-4876-a7e5-a9b584d8e6e6&type=display. Accessed February 4, 2024.

[8] Pfizer. Label: COVID-19 vaccine, mRNA (COMIRNATY). October 2024. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=48c86164-de07-4041-b9dc-f2b5744714e5&type=display. Accessed February 4, 2025.

[9] Edwards KM, Orenstein WA. COVID-19: vaccines. UpToDate. January 23, 2025.

[10] Centers for Disease Control and Prevention. CDC’s Role in Tracking Variants. July 1, 2024. https://www.cdc.gov/covid/php/variants/index.html. Accessed February 4, 2025.

[11] Califf RM. Vaccines for COVID-19: A personal reflection. January 13, 2025. https://www.fda.gov/news-events/fda-voices/vaccines-covid-19-personal-reflection. Accessed February 4, 2025.

[12] Graña C, Ghosn L, Evrenoglou T, et al. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022 Dec 7;12(12):CD015477.

[13] Califf RM. Vaccines for COVID-19: A personal reflection. January 13, 2025. https://www.fda.gov/news-events/fda-voices/vaccines-covid-19-personal-reflection. Accessed February 5, 2025.

[14] Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP). Grading of Recommendations, Assessment, Development (GRADE): updated COVID-19 vaccine (2024-2025 formulation). September 12, 2024. https://www.cdc.gov/acip/grade/covid-19-2024-2025-6-months-and-older.html. Accessed February 5, 2025.

[15] Ibid.

[16] Worst Pill, Best Pills News. Very low risk of heart inflammation with COVID-19 mRNA vaccines. November 2022. https://www.worstpills.org/newsletters/view/1498. Accessed February 5, 2025.

[17] Califf RM. Vaccines for COVID-19: A personal reflection. January 13, 2025. https://www.fda.gov/news-events/fda-voices/vaccines-covid-19-personal-reflection. Accessed February 5, 2025.

[18] Ibid.