Durability of Protection against COVID-19 Breakthrough Infections and Severe Disease by Vaccines in the United States

Objectives: Determine durability of protection by the three currently available COVID-19 vaccines in the United States (US) following primary vaccination against breakthrough infections, hospitalizations, and intensive care unit (ICU) admissions. Methods: Using claims and laboratory data covering 168 million lives, we conducted a matched case-control study with fully vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing outcomes in months two through six following full vaccination were estimated relative to the first month after full vaccination for each vaccine separately. Results: Evidence of waning protection against infections started in month 2 from vaccination for both BNT162b2 (OR [95% CI] in month 6+, 2.93 [2.72, 3.15]) and mRNA-1273 (OR [95% CI] in month 6+, 2.76 [2.51, 3.04]), and in month 4 for Ad26.COV2.S (OR [95% CI] in month 5+, 1.31 [1.18, 1.47]). Evidence of waning protection against hospitalization started in month 2 for BNT162b2 (OR [95% CI], 3.97 [3.26, 4.83] in month 6+) and in month 3 for mRNA-1273 (OR 95% CI, 1.66 [1.26, 2.19] in month 6+). There was no evidence of waning protection against hospitalization for Ad26.COV2.S (OR [95% CI], 1.25 [0.86, 1.80] in month 5+). No waning of protection was observed at any time for ICU admissions for all three vaccines. Conclusions: Following primary vaccination, all three vaccines showed strong and durable protection against ICU admissions. Ad26.COV2.S showed a more durable level of protection against breakthrough infections and hospitalizations in line with published evidence of its durable antibody and cellular immune response, although its Vaccine Effectiveness (VE) at baseline after a single-dose is lower than that for the two-dose mRNA vaccines. Additional studies are needed to understand durability following homologous or heterologous boosters.