Moderna vs Pfizer in Delta
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Immune responses to mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccines decline by 6 months after vaccination, although antibody titers are higher with mRNA-1273. Comparison of vaccinated nonimmunocompromised adults showed lower risk of hospitalization for recipients of mRNA-1273 than BNT162b2 during March-August 2021.3 This study examined breakthrough infections, hospitalizations, and mortality in a general population for these 2 vaccines during the Delta period while considering risk characteristics of vaccine recipients and the varying time since vaccination.
Methods
We used the cloud-based TriNetX Analytics Platform to obtain web-based real-time secure access to fully deidentified electronic health records of 89 million patients from 63 health care organizations including inpatient and outpatient settings, representing 27% of the US population from 50 states covering diverse geographic, age, race and ethnicity, income, and insurance groups. TriNetX Analytics built-in functions allow for patient-level analyses. Because this study used only deidentified patient records, it was exempted from review by the Case Western Reserve University Institutional Review Board.We included breakthrough SARS-CoV-2 infections (defined by a positive laboratory test result for the presence of SARS-CoV-2 RNA) that occurred between July and November 2021, when the Delta variant predominated4 in fully vaccinated individuals receiving 2 doses of an mRNA vaccine (anytime between December 2020 and November 2021) who had no booster shot and no prior SARS-CoV-2 infection. Breakthrough infections were included if occurring 14 days after full vaccination. Monthly incidence rates of breakthrough infections (cases per 1000 person-days) were compared in those receiving mRNA-1273 vs BNT162b2. The 2 cohorts were propensity score matched for demographics, social determinants of health, transplants, and comorbidities previously associated with COVID-19 risk or severe outcomes5 (Table). Kaplan-Meier survival and Cox proportional hazard analyses were performed by following patients for 14 days after the index event (full vaccination), which accounted for time since vaccination. Hazard ratios (HRs) and 95% confidence intervals were calculated based on comparison of time-to-event rates in the 2 matched cohorts. Hospitalizations and mortality in infected patients for 60 days starting from the day of infection were compared between the propensity score–matched cohorts and COVID-19–related therapeutics.6 All statistical analyses were conducted within the TriNetX Analytics Platform with significance set at a 2-sided P < .05.
Results
The mRNA-1273 cohort (n = 62 628) was significantly older and had more comorbidities than the BNT162b2 cohort (n = 574 538), and the differences decreased after matching (Table). The monthly incidence rate of breakthrough infections increased from July to November 2021 in both cohorts, was higher in the BNT162b2 cohort than the mRNA-1273 cohort, and reached 2.8 and 1.6 cases per 1000 person-days in November, respectively (P < .001) (Figure). After matching, the mRNA-1273 cohort (n = 62 584) had a significantly lower hazard for breakthrough infections compared with the matched BNT162b2 cohort (n = 62 584) (HR, 0.85; 95% CI, 0.80-0.89).Among infected patients, mRNA-1273 recipients were older than BNT162b2 recipients, differed in sex and racial and ethnic composition, and had significantly more comorbidities and adverse social determinants of health, but differences were no longer significant after matching (Table). The 60-day hospitalization risk was 12.7% (392/3078) for mRNA-1273 recipients and 13.3% (2489/18 737) for BNT162b2 recipients. The 60-day mortality was 1.14% (35/3078) and 1.10% (207/18 737) for mRNA-1273 and BNT162b2 recipients, respectively. Among the matched cohorts, mRNA-1273 recipients (n = 3054) had a lower risk of 60-day hospitalizations than BNT162b2 recipients (n = 3054) (HR, 0.80; 95% CI, 0.70-0.91). No significant difference was observed for mortality (HR, 0.79; 95% CI, 0.50-1.23).
Discussion
This study found that recipients of mRNA-1273 compared with BNT162b2 had a lower risk of breakthrough SARS-CoV-2 infections and hospitalizations during the Delta period. Study limitations include that (1) the observational, retrospective nature of the study based on patient records could introduce selection, information, and follow-up biases; (2) generalizability of the results from the TriNetX platform is unknown; (3) differences between cohorts in geographic distribution and virus circulation could confound the results; and (4) the cohorts were similar after matching but small, statistically significant differences in some characteristics remained. However, those differences would lead to an underestimation of the differences between vaccines.
