Bivalent Boosters and Risk of Postacute Sequelae Following Vaccine-Breakthrough SARS-CoV-2 Omicron Infection: A Cohort Study.

Abstract

Vaccination has been shown to attenuate the risk of postacute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no prior population-based studies have evaluated if updated bivalent boosters reduce risk of postacute sequelae following Omicron variant infection, versus ancestral vaccines. National databases were utilized to construct a population-based cohort of adult individuals infected during Omicron-predominant transmission. Risk and excess burden (EB) of prespecified multiorgan 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 messenger RNA (mRNA) vaccines, using competing-risks regression. A total of 1 080 348 vaccine-breakthrough infections after an ancestral mRNA booster were contrasted against 9824 vaccine-breakthrough infections following a bivalent mRNA booster. There was an estimated 37.8% (hazard ratio [HR], 0.62 [95 confidence interval {CI}, .53-.73]) decrease in risk and lower overall EB per 1000 (-28.73 [95% CI, -40.47 to -16.99]) of any postacute sequelae, as well as a 39.9% (HR, 0.62 [95% CI, .52-.73]) decrease in risk and lower EB (-22.95 [95% CI, -32.71 to -13.19]) of any postacute neurological sequelae, among individuals who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines. Specifically, there was reduced risk of thrombotic disorders (HR, 0.54 [95% CI, .29-.99]), episodic neurological disorders (HR, 0.55 [95% CI, .43-.72]), movement disorders (HR, 0.57 [95% CI, .47-.70]), and autoimmune vasculitis (HR, 0.54 [95% CI, .29-.99]) 31-365 days postinfection among those who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines. Boosting with updated bivalent mRNA vaccines was associated with greater attenuation of risk for postacute sequelae following Omicron variant infection, compared with ancestral mRNA boosters.