Bivalent boosters and risk of post-acute sequelae following vaccine-breakthrough SARS-CoV-2 Omicron infection: a cohort study.

Background: Vaccination has been shown to attenuate the risk of post-acute sequelae following SARS-CoV-2 infection. However, no prior population-based studies have evaluated if updated bivalent boosters reduce risk of post-acute sequelae following Omicron-variant infection, versus ancestral vaccines.

Methods: National databases were utilised to construct a population-based cohort of adult individuals infected during Omicron-predominant transmission. Risk and excess-burdens (EB) of pre-specified multi-organ new-incident diagnoses at 31-365 days post-SARS-CoV-2 infection were compared between individuals who received prior bivalent boosters, and those boosted with ancestral mRNA vaccines, using competing-risks regression.

Results: 1,080,348 vaccine-breakthrough infections after an ancestral mRNA booster were contrasted against 9,824 vaccine-breakthrough infections following a bivalent mRNA booster. There was an estimated 37.8% (hazards-ratio, HR: 0.62 [0.53, 0.73]) decrease in risk and lower overall excess burden per 1000 (EB:-28.73 [-40.47, -16.99]) of any post-acute sequelae, as well as a 39.9% (HR: 0.62 [0.52, 0.73]) decrease in risk and lower excess burden (EB: -22.95 [-32.71, -13.19]) of any post-acute neurological sequelae, amongst individuals who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines. Specifically, there was reduced risk of thrombotic disorders (HR: 0.54 [0.29, 0.99]), episodic neurological disorders (HR: 0.55 [0.43, 0.71]), movement disorders (HR: 0.57 [0.47, 0.70]), and autoimmune vasculitis (HR: 0.54 [0.29, 0.99]) 31-365 days post-infection amongst who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines.

Interpretation: Boosting with updated bivalent mRNA vaccines was associated with greater attenuation of risk for post-acute sequelae following Omicron-variant infection, compared with ancestral mRNA boosters.