ABSTRACT
Background: Long-term effectiveness of COVID-19 mRNA boosters in populations with different prior infection histories and clinical vulnerability profiles is inadequately understood. Method(s): A national, matched, retrospective, target trial cohort study was conducted in Qatar to investigate effectiveness of a third mRNA (booster) dose, relative to a primary series of two doses, against SARS-CoV-2 omicron infection and against severe COVID-19. Associations were estimated using Cox proportional-hazards regression models. Result(s): Booster effectiveness relative to primary series was 41.1% (95% CI: 40.0-42.1%) against infection and 80.5% (95% CI: 55.7-91.4%) against severe, critical, or fatal COVID-19, over one-year follow-up after the booster. Among persons clinically vulnerable to severe COVID-19, effectiveness was 49.7% (95% CI: 47.8-51.6%) against infection and 84.2% (95% CI: 58.8-93.9%) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 57.1% (95% CI: 55.9-58.3%) in the first month after the booster but waned thereafter and was modest at only 14.4% (95% CI: 7.3-20.9%) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2.75* subvariant incidence, effectiveness was progressively negative reaching -20.3% (95% CI: -55.0-29.0%) after one year of follow-up. Similar levels and patterns of protection were observed irrespective of prior infection status, clinical vulnerability, or type of vaccine (BNT162b2 versus mRNA-1273). Conclusion(s): Boosters reduced infection and severe COVID-19, particularly among those clinically vulnerable to severe COVID-19. However, protection against infection waned after the booster, and eventually suggested an imprinting effect of compromised protection relative to the primary series. However, imprinting effects are unlikely to negate the overall public health value of booster vaccinations.
ABSTRACT
Background: Coronavirus Disease 2019 (COVID-19) vaccine antigen dosage may affect protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but direct evidence to quantify this effect is lacking. Method(s): A matched, retrospective, cohort study that emulated a randomized control trial was conducted in Qatar between February 3, 2022 and November 8, 2022, to provide a head-to-head, controlled comparison of protection induced by two antigen dosages of the BNT162b2 vaccine. The study compared incidence of omicron infection in the national cohort of adolescents 12 years of age who received the two-dose primary-series of the 30-mug BNT162b2 vaccine to that in the national cohort of adolescents 11 years of age who received the two-dose primary-series of the pediatric 10-mug BNT162b2 vaccine. Associations were estimated using Cox proportional-hazard regression models. Result(s): Among adolescents with no record of prior infection, cumulative incidence of infection was 6.0% (95% CI: 4.9-7.3%) for the 30-mug cohort and 7.2% (95% CI: 6.1-8.5%) for the 10-mug cohort, 210 days after the start of follow-up. Incidence during follow-up was dominated by omicron subvariants including, consecutively, BA.1/BA.2, BA.4/BA.5, BA.2.75*, and XBB. The adjusted hazard ratio comparing incidence of infection in the 30-mug cohort to the 10-mug cohort was 0.77 (95% CI: 0.60-0.98). Corresponding relative effectiveness was 23.4% (95% CI: 1.6-40.4%). Relative effectiveness was -3.3% (95% CI: -68.0- 27.5%) among adolescents with a record of prior infection. Conclusion(s): Three-fold higher BNT162b2 dosage was associated with ~25% higher protection against infection in infection-naive adolescents of similar age. These findings may inform design of future COVID-19 vaccines and boosters for persons of different age groups.
ABSTRACT
Background. Protection offered by five different forms of immunity, combining natural and vaccine immunity, was investigated against symptomatic SARS-CoV-2 infection from Omicron BA.1 or BA.2, and severe, critical, or fatal COVID-19 from BA.1 or BA.2, in Qatar, between December 23, 2021 and February 21, 2022. Methods. Six national, matched, test-negative case-control studies were conducted on a sample of 272,861 PCR-positive tests and 669,628 PCR-negative tests to estimate effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination. Results. Effectiveness of prior infection alone against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of two-dose BNT162b2 vaccination alone was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all individuals received their second dose >6 months earlier. Effectiveness of three-dose BNT162b2 vaccination alone was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%). Effectiveness of hybrid immunity of prior infection and three-dose BNT162b2 vaccination was 77.3% (95% CI: 72.4-81.4%). Meanwhile, prior infection, BNT162b2 vaccination, and hybrid immunity all showed strong effectiveness ( >70%) against severe, critical, or fatal COVID-19 due to BA.2. Similar patterns of effectiveness were observed for BA.1 and for the mRNA-1273 vaccine. Conclusion. There are no discernable differences between BA.1 and BA.2 in the effects of prior infection, vaccination, and hybrid immunity. Vaccination enhances the protection of those with a prior infection. Hybrid immunity resulting from prior infection and recent booster vaccination conferred the strongest protection.