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South African researchers report waning monovalent (single-strain) COVID-19 vaccine booster effectiveness against the Omicron subvariants, with estimated efficacy falling to 50% against the BA.1/BA.2 and 47% against BA.4/BA.5 as early as 3 or 4 months after vaccination.
In the study, published yesterday in the New England Journal of Medicine (NEJM), the research team estimated the effectiveness of two and three doses of the monovalent Pfizer/BioNTech vaccine against COVID-19 hospitalization among 32,883 patients hospitalized for any cause and tested for COVID-19 from Nov 15, 2021, to Jun 24, 2022.
They used a test-negative design to estimate the odds of vaccination among patients who tested positive for COVID-19.
The study was conducted before the Aug 31 US Food and Drug Administration (FDA) authorization of the updated bivalent (two-strain) boosters designed to protect against BA.4/BA.5, in addition to the wild-type virus (BA.4/BA.5 has superseded BA.1/BA.2). The new Pfizer booster is authorized for ages 12 and older, while the Moderna booster is authorized only for adults. The older booster is no longer in use.
From Nov 15, 2021, to Feb 28, 2022 (BA.1/BA.2-dominant period) and Apr 15 to Jun 24, 2022 (BA.4/BA.5-dominant period), 18% of patients tested positive for COVID-19. During both periods, two-dose effectiveness against hospitalization began waning as early as 3 or 4 months after vaccination.
Estimated vaccine effectiveness was 56.3% (95% confidence interval [CI], 51.6% to 60.5%) during BA.1/BA.2 dominance and 47.4% (95% CI, 19.9% to 65.5%) amid BA.4/BA.5. A third dose remained effective against severe infections with all four subvariants at 1 or 2 months, but effectiveness fell by 3 or 4 months to 50% (95% CI, 4.4% to 73.9%) amid BA.1/BA.2 dominance and 46.8% (95% CI, 35.3% to 56.2%) during the BA.4/BA.5 period.
“The evidence of rapid waning of durability indicates the need for regular boosting as early as 4 months after the last dose or the need for vaccines to incorporate variants of concern to maintain protection,” the authors concluded.
Sep 14 NEJM research letter
Today Centers for Disease Control and Prevention (CDC) researchers published new data in Morbidity and Mortality Weekly Report showing that the risk of death among hospitalized COVID-19 patients was substantially lower during the later Omicron period than during the earlier Omicron period or the Delta period, even though more elderly patients were hospitalized during the later Omicron period.
The authors used a large US hospital database composed of 678 hospitals to look at in-hospital mortality risk during the Delta (July–October 2021), early Omicron (January–March 2022), and later Omicron (April–June 2022) variant periods among patients hospitalized primarily for COVID-19.
From April 2020 to June 2022, a total of 1,072,106 COVID-19 hospitalizations and 128,517 in-hospital deaths were reported.
Before the Omicron variant emerged as the dominant strain in the United States, COVID-19 hospitalizations identified as primarily for COVID-19 were 83.8%, (95% confidence interval [CI], 83.7% to 83.9%) and fell during the Omicron period to 62.8% (95% CI, 62.6% to 63.0%). Among patients hospitalized primarily for COVID-19 during the Delta, early Omicron, and later Omicron periods, patients aged 65 years or older constituted 15.1%, 22.9%, and 28.9% of all COVID patients, respectively.
The authors found the crude mortality risk (cMR, recorded as deaths per 100 patients hospitalized primarily for COVID-19) was lower during the early Omicron (13.1) and later Omicron (4.9) periods than during the Delta (15.1) period.
“During the later Omicron period, 81.9% of in-hospital deaths occurred among adults aged ≥65 years and 73.4% occurred among persons with three or more underlying medical conditions,” the authors wrote. “Vaccination, early treatment, and appropriate nonpharmaceutical interventions remain important public health priorities for preventing COVID-19 deaths, especially among persons most at risk.”
Sep 16 MMWR study

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