MRNA booster shot durably bolsters defenses against severe COVID-19

Boosting with an mRNA vaccine yields significant protection against severe COVID-19 and may keep people out of the hospital for up to 6 months, as shown in a Singapore study.

A group of researchers based locally evaluated the effectiveness and waning of mRNA and inactivated SARS-CoV-2 vaccination against confirmed infection and severe COVID-19 among 2,441,581 eligible individuals (52.4 percent women) aged ≥30 years during a large Omicron wave.

“We found that mRNA vaccine boosting was associated with a marked increase in protection against severe COVID-19 compared with 5 months after two-dose mRNA vaccination, with no waning observed for up to 6 months after the booster dose and no sustained difference comparing the different mRNA vaccine combinations,” they said.

The estimated mRNA booster effectiveness was 87.4 percent (95 percent confidence interval [CI], 83.3–90.5) 15–60 days after boosting and 87.2 percent (95 percent CI, 84.2–89.7) 5–6 months after boosting. In comparison, booster effectiveness between 15 and 330 days after three-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6 percent (95 percent CI, 48.7–81.9). [JAMA Netw Open 2022;5:e2228900]

“Similarly, two-dose mRNA vaccination protection against severe COVID-19 did not show evidence of waning,” the researchers said.

“These results suggest that booster mRNA vaccine protection was durable against severe COVID-19 over 6 months regardless of vaccine combination, and three-dose inactivated SARS-CoV-2 vaccination provided greater protection than two-dose inactivated SARS-COV-2 vaccine but less protection compared with three-dose mRNA,” they added.

Confirmed infection

In terms confirmed infection, protection against Omicron in the first 2 months after a booster mRNA dose was similar to that seen in the first 2 months after the second mRNA dose. The estimated effectiveness of mRNA booster ranged from 31.7 percent to 41.3 percent across the following boosting combinations: homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and two-dose mRNA-1273/BNT162b2 booster.

However, protection against confirmed infection 5 months and more after mRNA boosting waned rapidly, with the estimated effectiveness ranging from –2.8 percent to 14.6 percent.

Three-dose inactivated SARS-CoV-2 vaccines, on the other hand, provided significantly less protection against confirmed infection over 2 months after the latest vaccine dose as compared with the period immediately after two-dose mRNA vaccination.

Severe disease prevention a key goal

In February this year, Singapore required a booster mRNA vaccine dose 5 months (and no later than 9 months) after a two-dose mRNA or three-dose inactivated SARS-CoV-2 vaccine regimen to remain fully vaccinated, a status designation that influences an individual’s social distancing and workplace restrictions. [https://file.go.gov.sg/vdsmminfo.pdf]

This move to include a booster shot was in response to a large spike in COVID-19 cases fuelled by the Omicron variant. Accordingly, a booster dose in this study was defined as a third dose of vaccine after a two-dose mRNA or inactivated SARS-CoV-2 series. [https://tinyurl.com/y95oyub6]

In the study population, 2,201,604 (90.2 percent) participants had received a three-dose vaccination by 10 March 2022, of whom 97.8 percent had received three doses of an mRNA vaccine and 2.2 percent three doses of an inactivated SARS-CoV-2 vaccine. There were 319,943 (13.1 percent) confirmed SARS-CoV-2 infections, of which 1,513 (0.4 percent) were severe COVID-19 cases. 

Even though mRNA booster protection against confirmed infection waned to preboosting levels within approximately 6 months following boosting, the researchers stressed that the prevention of severe disease is the key goal of COVID-19 vaccination.

“Our results support consideration of boosting following a two-dose mRNA or three-dose inactivated SARS-CoV-2 vaccine regimen [to prevent severe COVID-19],” the researchers continued.

Whereas a fourth mRNA vaccine dose is not required in the 6-month period after a booster dose in the general adult population, Singapore recommends a fourth mRNA vaccine dose for selected subpopulations, “specifically persons aged ≥80 years, persons living in aged care facilities, and persons with medical risk factors for severe COVID-19,” they said. [https://tinyurl.com/ycr5rwv8]

The researchers called for longer follow-up data to determine if severe COVID-19 protection wanes after 6 months.