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Three doses of mRNA vaccine was effective against severe COVID-19 for both immunocompetent and immunocompromised adults during the Delta wave, researchers found.

From Aug. to Dec. 15, 2021, vaccine effectiveness (VE) against COVID-related hospitalization was 97% (95% CI 95-99) for immunocompetent adults who received a two-dose Pfizer or Moderna series followed by a booster dose and 88% (95% CI 81-93) for immunocompromised adults who received three doses of vaccine, reported Mark Tenforde, MD, PhD, of the CDC, and colleagues.

Not surprisingly, VE against hospitalization was lower with the two-dose primary series alone for both immunocompetent (82%, 95% CI 77-86) and immunocompromised adults (69%, 95% CI 57-78), the authors wrote in the .

Interestingly, a sensitivity analysis among patients with CDC-defined moderately to severely immunocompromising conditions showed a VE of 87% (95% CI 78-92) with three doses versus 65% (95% CI 49-76) with two doses.

Tenforde's team examined data from the (IVY Network). Case patients had COVID-like illness and tested positive for SARS-CoV-2 via nucleic acid amplification test (NAAT), while controls were hospitalized with or without COVID-like illness, but tested negative via NAAT.

Overall, they analyzed data from 2,952 hospitalized patients, 1,385 cases and 1,567 controls. Of these, 36% had an immunocompromising condition. Median patient age was 62 years, 51% were men, and 58% were non-Hispanic white.

Among the case patients, two-thirds were unvaccinated, while 29% received two doses and 3% received three doses. Among controls, 29% were unvaccinated, while 54% received two and 17% received three doses, respectively.

Not surprisingly, a higher proportion of immunocompromised patients were case patients (34%) than controls (20%, P<0.001).

Tenforde's group noted that these findings may be especially relevant during the current Omicron period, as "early evidence suggests that a third mRNA vaccine dose elicits markedly stronger neutralizing antibody responses to the Omicron variant compared with responses to two vaccine doses, and increases VE against severe disease following infection with the Omicron variant," they wrote.

They reiterated the importance of immunocompromised adults receiving a third dose of mRNA vaccine at least 28 days after their second dose. In October, CDC also recommended that certain moderately or severely immunocompromised individuals should get a booster dose at least 6 months after completing their third dose, which has since been .

The agency also recommends booster doses of Pfizer or Moderna vaccine for all individuals ages 12 and up, at least 5 months after a two-dose primary series.

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