ABSTRACT
BackgroundThe duration of protection afforded by Covid-19 vaccines in the United States is unclear. Whether the recent increase of breakthrough infections was caused by waning immunity to the primary vaccination or by emergence of new variants that are more highly transmissible is also unknown. MethodsWe extracted data on vaccination histories and clinical outcomes (Covid-19, hospitalization, death) for the period from December 13, 2020 through September 8, 2021 by linking data from the North Carolina COVID-19 Surveillance System and COVID-19 Vaccine Management System covering [~]10.6 million residents statewide. We used the Kaplan-Meier method to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) vaccines in reducing the incidence of Covid-19 over successive post-vaccination time periods, producing separate estimates for individuals vaccinated during different calendar periods. In addition, we used Cox regression with time-dependent vaccination status and time-varying hazard ratios to estimate the effectiveness of the three vaccines in reducing the hazard rates or current risks of Covid-19, hospitalization, and death, as a function of time elapsed since the first dose. ResultsFor the Pfizer two-dose regimen, vaccine effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 94.9% (95% confidence interval [CI], 94.5 to 95.2) at 2 months (post the first dose) and drops to 70.1% (95% CI, 68.9 to 71.2) after 7 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 96.4% (95% CI, 94.7 to 97.5) at 2 months and remains at 87.7% (95% CI, 84.3 to 90.4) at 7 months; effectiveness in reducing the current risk of death ramps to 95.9% (95% CI, 92.9 to 97.6) at 2 months and is maintained at 88.4% (95% CI, 83.0 to 92.1) at 7 months. For the Moderna two-dose regimen, vaccine effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 96.0% (95% CI, 95.6 to 96.4) at 2 months and drops to 81.9% (95% CI, 81.0 to 82.7) after 7 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 97.5% (95% CI, 96.3 to 98.3) at 2 months and remains at 92.3% (95% CI, 89.7 to 94.3) at 7 months; effectiveness in reducing the current risk of death ramps to 96.0% (95% CI, 91.9 to 98.0) at 3 months and remains at 93.7% (95% CI, 90.2 to 95.9) at 7 months. For the Janssen one-dose regimen, effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 79.0% (95% CI, 77.1 to 80.7) at 1 month and drops to 64.3% (95% CI, 62.3 to 66.1) after 5 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 89.8% (95% CI, 78.8 to 95.1) at 2 months and stays above 80% through 5 months; effectiveness in reducing the current risk of death ramps to 89.4% (95% CI, 52.3 to 97.6) at 3 months and stays above 80% through 5 months. For all three vaccines, the ramping and waning patterns are similar for individuals who were vaccinated at different dates, and across various demographic subgroups (age, sex, race/ethnicity, geographic region, county-level vaccination rate). ConclusionsThe two mRNA vaccines are remarkably effective and durable in reducing the risks of hospitalization and death. The Janssen vaccine also offers a high level of protection against hospitalization and death. The Moderna vaccine is significantly more durable than the Pfizer vaccine in reducing the risk of Covid-19. Waning vaccine effectiveness is caused primarily by declining immunity rather than emergence of new variants. It would be worthwhile to investigate the effectiveness of the Janssen vaccine as a two-dose regimen, with the second dose given approximately 1-2 months after the first dose.
