How Long Did the Original mRNA COVID-19 Vaccines Protect Against the Worst Outcomes? A Year of Omicron Data

By April 2023, COVID-19 had killed about 1.1 million people in the United States, roughly 75% of them aged 65 or older. The original, monovalent mRNA vaccines were known to prevent hospitalization, and to prevent critical illness — being put on a breathing machine, or dying — during the Alpha, Delta and early Omicron waves. During Omicron, though, their protection against infection, outpatient illness and hospitalization had been seen to wane quickly. How long did protection against the most severe outcomes last?

That question mattered for deciding how often to revaccinate. Most adults had only ever had monovalent doses: a bivalent booster was recommended from September 1, 2022, but only 20% of adults had received one. And measuring protection against critical illness sidesteps a bias in hospitalization figures, where routine COVID-19 testing on admission catches patients who are in hospital for something else.

The study

The IVY Network (Investigating Respiratory Viruses in the Acutely Ill) enrolled adults admitted with COVID-19–like illness to 24 hospitals in 19 states from February 1, 2022, to January 31, 2023, and compared:

Left out were people who were immunocompromised, had a non-mRNA or only one mRNA dose, had a bivalent dose, or tested positive for flu (because people's COVID-19 and flu vaccination habits are linked). Results were adjusted for region, calendar time, age, sex, race and ethnicity.

Of 6,354 patients enrolled, 4,421 (70%) were analysed: 362 cases and 4,059 controls. Their median age was 64; 91% had at least one chronic condition, and 20% had had COVID-19 before.

Of the cases, 293 (81%) were ventilated and 156 (43%) died in hospital within 28 days.

The results

Vaccine effectiveness against ventilation or death in hospital:

By time since the last dose (median 248 days):

Protection was highest in the first six months, though the confidence intervals of the later estimates overlapped with it. Within each time window, the number of doses made no significant difference: protection tracked time since the last dose more closely than how many doses someone had.

What it means

• The original mRNA vaccines gave substantial and lasting protection against the worst outcomes of COVID-19 through a full year of Omicron — including for people 65 and older, the group at highest risk.
• There was some waning after six months, but clinically meaningful protection lasted a year or more. Evidence from the United Kingdom is consistent: among adults 65 and older during Omicron, protection against death 40 weeks (280 days) after vaccination was 49.7% with two doses and 56.9% with three.
• The greatest benefit comes in the first six months after a dose — worth weighing, with COVID-19 trends and people's risk factors, when planning revaccination schedules.

On April 18, 2023, the bivalent vaccines became the only mRNA COVID-19 vaccines authorized in the United States. At the time, only 42% of adults 65 and older had received a bivalent dose, and CDC recommended that all adults stay up to date, including the bivalent vaccine and, for those at highest risk, optional extra bivalent boosters.

Limits

• Too few cases to estimate protection separately for each Omicron subvariant period, or by both time since dose and number of doses at once.
• Some cases may have been ventilated or died for reasons other than COVID-19, which would make the vaccines look less effective.
• Prior infection was rarely recorded, so its effect couldn't be assessed.
• Despite adjustment, other factors — such as antiviral treatment — may have skewed results.

Sources

Based on DeCuir J, Surie D, Zhu Y, et al., "Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19–Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period — IVY Network, 19 U.S. States, February 1, 2022–January 31, 2023," MMWR volume 72, number 17, Centers for Disease Control and Prevention, with authors from CDC and academic medical centers and health systems across the IVY Network; a work of the United States government in the public domain.