For a study, researchers sought to assess the relationships between symptomatic SARS-CoV-2 infection and the receipt of BNT162b2, mRNA-1273, and Ad26.COV2.S by day since vaccination before and after Delta variant dominance (pre-Delta period: March 13-May 29, 2021; Delta period: July 18-October 17, 2021). In the pharmacy-based Increasing Community, Access to the Testing platform, a test-negative, the case-control design was used using data from 6884 US COVID-19 testing locations. From March 13 to October 17, 2021, 1 634 271 laboratory-based SARS-CoV-2 nucleic acid amplification tests (NAATs) from adults 20 years and older and 180 112 NAATs from adolescents 12 to 19 years old with COVID-19–like illness were included in the investigation. COVID-19 immunization (one Ad26.COV2.S dosage or two mRNA doses) 14 days before. The odds ratio (OR) using spline-based multivariable logistic regression was used to assess the relationship between symptomatic infection and previous immunization.

The study comprised 390 762 test-positive cases (21.5%) and 1 423 621 test-negative controls (78.5%). (59.9% were 20-44 years; 9.9% were 12-19 years; 58.9% were female; 71.8%were White). The BNT162b2 mean OR for days 14 to 60 following a second dose (initial OR) was lower during the pre-Delta era (0.10 [95% CI, 0.09-0.11]) than during the Delta period (0.16 [95% CI, 0.16-0.17]) and rose with time since immunization in people 20 years and older (per-month change in OR, pre-Delta: 0.04 [95% CI, 0.02-0.05]; Delta: 0.03 [95% CI, 0.02-0.03]). During the pre-Delta era, the mRNA-1273 OR was 0.05 (95% CI, 0.04-0.05), 0.10 (95% CI, 0.10-0.11) during the Delta period, and rose over time (per-month change in OR, pre-Delta: 0.02 [95% CI, 0.005-0.03]; Delta: 0.03 [95% CI, 0.03-0.04]). The initial OR for Ad26.COV2.S was 0.42 (95% CI, 0.37-0.47) in the pre-Delta period and 0.62 (95% CI, 0.58-0.65) in the Delta era, and it did not rise substantially with time following vaccination. The initial OR for BNT162b2 during the Delta period was 0.06 (95% CI, 0.05-0.06) among 12- to 15-year-olds, increasing by 0.02 (95% CI, 0.01-0.03) each month, and 0.10 (95% CI, 0.09-0.11) among 16- to 19-year-olds, increasing by 0.04 (95% CI, 0.03-0.06) per month. 

The OR for the connection between symptomatic SARS-CoV-2 illness and COVID-19 immunization (as an indicator of vaccine efficacy) was greater among adults during Delta variant predominance, implying weaker protection. The constant increase in OR by the month following immunization for mRNA vaccine was consistent with attenuation of anticipated efficacy with time; attenuation related to time was larger than that related to variation.