COVID-19 breakthrough infections in vaccinated participants of the Safety and Efficacy of Preventative COVID Vaccines sub-study

BACKGROUND: The rate of breakthrough infection in vaccinated Ontarians during the Omicron wave is unknown. METHODS: Active participants of the Safety and Efficacy of Preventative COVID Vaccines (STOPCoV) study (892 >age 70 years and 369 aged 30–50 years) were invited to participate in a sub-study evaluating breakthrough COVID-19 infection. Self-administered rapid antigen tests (RAT) were reported twice weekly and symptom questionnaires weekly for 6 weeks. The primary outcome was the proportion reporting positive RAT. RESULTS: 806 e-consented, 727 (90%) completed >1 RAT with total 7,116 RATs completed January 28–March 29, 2022. Twenty out of twenty-five with a positive RAT had a booster vaccine prior to the positive test. All cases were mild, none requiring hospitalization. Nineteen had positive dried blood spot analysis for IgG antibody to the receptor binding domain (RBD) prior to the positive RAT. The mean (SD) of the normalized IgG ratio to RBD was 1.22 (0.29) for younger and 0.98 (0.44) for older participants, values similar to corresponding ratios for those without positive RAT and those in the main cohort. 105 participants reported one and 96 reported >2 possible COVID-19 symptoms despite negative RAT. The false negative RAT was low (4% to 6.6 %) compared to subsequent positive nucleoprotein antibody. CONCLUSIONS: Positive RAT for COVID-19 was infrequent (3.4%). We were unable to determine a protective antibody level against breakthrough infection. Our findings can inform public health COVID-19 restrictions guidelines. Our decentralized study provides a model for rapid institution of new questions during a pandemic.