Comparative effectiveness of bivalent BA.4.5 or BA.1 mRNA booster vaccines among immunocompromised individuals across three Nordic countries: a nationwide cohort study
Authors: Gram Mie Agermose , Thiesson Emilia Myrup , Pihlström Nicklas , Perälä Jori , Poukka Eero , Leino Tuija , Ljung Rickard , Andersson Niklas Worm , Hviid Anders 
Published: May 2024

AbstractObjectivesTo estimate the effectiveness and waning immunity of the bivalent BA.4-5 or BA.1 mRNA booster vaccine against Covid-19-related hospital admission and death in immunocompromised individuals.DesignNationwide cohort analyses using a matched cohort design.SettingDenmark, Finland, and Sweden, from 1 September 2022 to 31 October 2023.ParticipantsAll individuals aged 18 years or above with medical history of at least one immunocompromised condition, residency in Denmark, Finland or Sweden, no history of Covid-19-related hospitalization, and receipt of at least three Covid-19 vaccine doses as of study start, 1 September 2022. Individuals boosted with a BA.4-5 or BA.1 vaccine were matched 1:1 with unboosted individuals.Main outcome measuresCountry-combined vaccine effectiveness (VE) estimates against Covid-19 hospitalization and Covid-19- related death at day 270 of follow-up. Potential waning was assessed in 45-day intervals.ResultsA total of 352,762 BA.4-5 and 191,070 BA.1 booster vaccine doses were administered to immunocompromised individuals. At day 270, the comparative VE against Covid-19 hospitalization was 34.2% (95% CI, 7.1% to 61.3%) for the bivalent BA.4-5 vaccine (696 vs 1,128 events, risk difference [RD] per 100,000, -223.7, 95% CI, -411.5 to -36.0) and 42.6% (95% CI, 31.3% to 53.9%) for the BA.1 vaccine (395 vs 740 events, RD per 100,000, -385.0, -673.4 to -96.6) compared with matched unboosted. The comparative VE against Covid-19 death was 53.9% (95% CI, 38.6% to 69.3%) for the bivalent BA.4-5 vaccine (203 vs 457 events, RD per 100,000, -138.7, 95% CI, -195.5 to -81.9) and 57.9% (95% CI, 48.5% to 67.4%) for the BA.1 vaccine (112 vs 302 events, RD per 100,000, -220.6, -275.9 to -165.4). The VE estimates were highest in the first 45 days since eight days after vaccination (52.8% and 72.8% for bivalent BA.4-5 vaccine against Covid-19-related hospitalization and death, and 62.2% and 84.2% for bivalent BA.1 vaccine) and waned gradually during the 270 days of follow-up.ConclusionsIn immunocompromised individuals, vaccination with a bivalent BA.4-5 or BA.1 booster lowered the risk of Covid-19-related hospitalization and death over a follow-up period of 9 months. The effectiveness was highest during the first months since vaccination with subsequent gradual waning.Summary boxWhat is already known on this topicBivalent BA.4-5 or BA.1 booster vaccination increases protection against severe Covid-19 outcomes in the general population.Lower effectiveness of the original monovalent Covid-19 vaccines among immunocompromised individuals has been observed relative to the effectiveness within the general population.What this study addsBivalent BA.4-5 or BA.1 booster vaccination increased the protection against Covid-19 outcomes among immunocompromised individuals.At day 270 of follow-up, the bivalent BA.4-5 booster had prevented 223.7 hospitalizations and 138.7 deaths related to Covid-19 per 100,000 boosted individuals. For the bivalent BA.1 booster, corresponding numbers were 385.0 and 220.6, respectively.The vaccine effectiveness was highest during the first 45 days since eight days after vaccination (52.8% and 72.8% for bivalent BA.4-5 vaccine against Covid-19-related hospitalization and death, and 62.2% and 84.2% for bivalent BA.1 vaccine) and waned gradually during the 270 days of follow-up.