COVID-19 Vaccines: Time to Boost Yet Again?

Volume 13, Issue 5

The COVID-19 saga continues, with news this week that the new BA.2 subvariant has become the dominant strain in the Northeast, and continues to become more common throughout the United States in general. This led the FDA to revoke sotrovimab’s EUA for 8 states in the Northeast, Puerto Rico, and the US Virgin Islands, given this agent—which was the only monoclonal antibody with activity against the original BA.1 strain—is not effective against BA.2.

We in the health care community find ourselves currently without any effective monoclonal antibody products to treat BA.2. While we do still have oral options, like Paxlovid, we are more vulnerable now with the demise of sotrovimab than we were last week. This naturally forces us to pivot to other avenues to manage COVID-19.

Just yesterday, the Centers for Disease Control and Prevention (CDC) issued new guidance on the use of a second booster shot for selected Americans. In this week’s issue of Talking Therapeutics, we discuss the new recommendations and offer guidance on who should get a fourth dose.

Point 1: Fourth Dose Effective in Preventing Death

The science to support an additional booster dose comes largely from an Israeli study, which found the overall mortality was reduced by 78% for adult patients over 60 years of age. The adjusted hazard ratio for death due to COVID-19 was .22, with a 95% confidence interval of .17 to .28.

While these numbers are impressive, I think looking at the relative effects of a second booster dose is important as well. In this paper, only .1% of patients with only 1 booster died. While this number was reduced to .03% with a second booster, these data show having only 3 doses of a mRNA COVID-19 vaccine still provides significant protection against severe disease and death.

These data, in my opinion, signal that a fourth dose of a mRNA vaccine is more optional than mandatory for most patients over 60 years of age. In other countries, for example, the age cutoff for a fourth shot is higher than the CDC recommendations. Germany has authorized a fourth shot for people over 70 years of age. The UK is recommending the second booster for people over the age of 75 years, and Sweden is giving fourth shots to people over 80 years of age.

Point 2: Those at Heightened Risk Should Get Second Booster

The CDC identified 50 years as the age cutoff for recommending a booster—as opposed to 60 years, which was the entry point for the Israeli study. The CDC’s decision was in recognition that younger people with selected comorbidities like diabetes may derive superior protection with a second booster. The current recommendations for a second booster also extend to those aged 12 years and up who have immunosuppressed conditions like active malignancy or solid organ transplantation.