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.
ABSTRACT
Background. Qatar experienced a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021 and peaked in mid-January, 2022. We investigated effects of Omicron subvariant (BA.1 and BA.2), previous vaccination, and prior infection on infectiousness of Omicron infections, between December 23, 2021 and February 20, 2022. The RT-qPCR cycle threshold (Ct) value of a SARS-CoV-2 infection represents the inverse of viral load and is correlated with culturable virus;thus, it can be used as a proxy for SARS-CoV-2 infectiousness. Methods. The study population included all individuals with an RT-qPCR-confirmed SARS-CoV-2 infection in Qatar in the study period. All relevant data for this population were extracted from the national, federated SARS-CoV-2 databases. A SARS-CoV-2 infection with BA.1 was proxied as an S-gene 'target failure' (SGTF) case, whereas infection with BA.2 was proxied as a non-SGTF case. The average Ct values of the N, ORF1ab, and S (if not an SGTF case) genes was used as the dependent variable. Univariable and multivariable regression analyses were conducted to estimate the association between Ct value and each of the Omicron subvariants, mRNA vaccination, prior infection, reason for RT-qPCR testing, study-period week of RT-qPCR test, and demographic factors. Results. Compared to BA.1, BA.2 was associated with 3.53 fewer cycles (95% CI: 3.46-3.60), signifying higher infectiousness (Table 1). Ct value decreased with time since second and third dose vaccinations. Ct values were highest for those who received their boosters in the month preceding the RT-qPCR test-0.86 cycles (95% CI: 0.72-1.00) higher than for unvaccinated persons. Ct value was 1.30 (95% CI: 1.20-1.39) cycles higher for those with a prior infection compared to those without prior infection, signifying lower infectiousness. Conclusion. BA.2 appears to be associated with substantially higher infectiousness than BA.1. This may reflect higher viral load and/or longer duration of infection, thereby explaining the rapid expansion of this subvariant in Qatar. Natural immunity from previous infection and strength of vaccine immunity correlated with less infectious breakthrough infections.
ABSTRACT
Background: SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. Methods: Leveraging the national databases, effects of vaccination and of prior infection on SARS-CoV-2 infectiousness were investigated by comparing the RT-qPCR cycle threshold (Ct) values (inversely correlated with viral load and culturable virus) in matched cohorts of primary infections in unvaccinated individuals, reinfections in unvaccinated individuals, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Pairwise comparisons were conducted assuming linear and non-linear relationships. Results: Through analyses of the randomly diagnosed infections, the mean Ct value was higher in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value was 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.8-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.4-4.6) cycles higher for reinfections in unvaccinated individuals. A sensitivity analysis assuming that infectiousness is non-linearly proportional to viral load yielded similar results. Conclusion: Differences imply that breakthrough infections are at least 50% less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.
ABSTRACT
Background: Reinfections with emerging SARS-CoV-2 variants are a serious concern. This study estimated the efficacy of immunity induced by natural infection against reinfection with B.1.351 and B.1.1.7 variants. Methods: Two retrospective matched cohort studies were conducted in Qatar from March 8-April 21 to assess reinfection in the national cohort of individuals with a prior PCR-confirmed infection and the national cohort of antibody-positive individuals, matching each in a 1:1 ratio by demographic characteristics to the national cohort of antibody-negative individuals. Incidence risks (using the Kaplan-Meier estimator), incidence rates, and efficacy of natural infection against reinfection were estimated. Results: In the study comparing 44,821 individuals with a prior PCR-confirmed infection to antibody-negative individuals, the efficacy of natural infection against reinfection was 92.3% (95% CI: 90.3-93.8%) for B.1.351, 97.6% (95% CI: 95.7-98.7%) for B.1.1.7, and 87.9% (95% CI: 84.7-90.5%) for unidentified variants (mostly suspected B.1.351 cases based on weekly sequencing analysis). In the second study, comparing 20,406 antibody-positive to antibody-negative individuals, efficacy was 86.4% (95% CI: 82.5-89.5%) for B.1.351, 96.4% (95% CI: 92.1-98.3%) for B.1.1.7, and 83.1% (95% CI: 77.2-87.5%) for unidentified variants. Additional analyses and sensitivity analyses confirmed these results, albeit with slightly lower efficacies. Conclusion: Natural infection with SARS-CoV-2 induces robust protection of 80-90% against reinfection with B.1.351 even a year after the primary infection, but lower than that against B.1.1.7.