Enhanced Vaccine Effectiveness during the Delta Phase of the COVID-19 Pandemic in the Medicare Population Supports a Multilayered Prevention Approach

Abstract

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.1.617.2 Delta variant phase of the pandemic in July and August 2021 in a cohort of 17 million Medicare beneficiaries of which 5.7 million were fully vaccinated. We found that individuals fully vaccinated with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines in January 2021 had 2.5 times higher breakthrough infections and hospitalizations than those fully vaccinated in March 2021, consistent with waning of vaccine-induced immunity. Measuring VE weekly, we found that VE against hospitalization, and even more so against infection, increased from July 2021 through August 2021, suggesting that in addition to the protective role of vaccination, increased masking or social distancing might have contributed to the unexpected increase in VE. Ongoing monitoring of Medicare beneficiaries should be a priority as new variants continue to emerge, and the VE of the new bivalent vaccines remains to be established. This could be accomplished with a large Medicare claims database and the analytics platform used for this study.

Keywords: B.1.617.2; BNT162b2 vaccine; COVID-19/breakthrough infection; COVID-19/epidemiology/prevention & control; Delta variant; Medicare; SARS CoV-2; aged 65 and over; mRNA-1273 vaccine; multilayered prevention; vaccine effectiveness.

Figure 1

COVID-19 Infection and Hospitalization Rates in Vaccinated and Unvaccinated Individuals during the Delta Variant Phase of the Pandemic. (A)—Weekly infection rates per 100 K vaccinated (blue line) and unvaccinated (red line) individuals. (B)—Weekly hospitalization rates per 100 K vaccinated (blue line) and unvaccinated (red line) individuals. Weekly SARS-CoV-2 Delta variant prevalence reported by the CDC (gray dashed line).

Figure 2

COVID-19 Vaccine Effectiveness against Infection and Hospitalization during the Delta Variant Phase of the Pandemic. Vaccine effectiveness estimates against infection (green curve with 95% CI shown in green shaded area) and against hospitalization (black curve with 95% CI shown in gray shaded area). Weekly SARS-CoV-2 Delta variant prevalence reported by the CDC (gray dashed line).

Figure 3

COVID-19 Breakthrough Infection and Hospitalization Rates in Individuals Vaccinated in January versus March 2021. (A)—Weekly infection rates per 100 K individuals vaccinated in January 2021 (red bars) vs. vaccinated in March 2021 (purple bars). (B)—Weekly hospitalization rates per 100 K individuals vaccinated in January 2021 (red bars) vs. vaccinated in March 2021 (purple bars). Weekly SARS-CoV-2 variant prevalence reported by the CDC (gray dashed line). Error bars indicate 95% CI. Asterisks shown above the bars indicate p values for weekly rates for those vaccinated in January 2021 being greater than weekly rates for those vaccinated in March 2021. *** p < 0.001 by two-proportion Z-test.

Figure 4

COVID-19 breakthrough infection and hospitalization rates in individuals vaccinated in the January Group vs. those vaccinated in the March Group with either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. (A)—Weekly infection rates per 100 K individuals vaccinated in the January Group (red bars) vs. those vaccinated in the March Group (purple bars), with either the Pfizer-BioNTech BNT162b2 (solid bars) or the Moderna mRNA-1273 (striped bars) vaccines. (B)—Weekly hospitalization rates per 100 K individuals vaccinated in the January Group (red bars) vs. those vaccinated in the March Group (purple bars), with either the Pfizer-BioNTech BNT162b2 (solid bars) or the Moderna mRNA-1273 (striped bars) vaccine. Weekly SARS-CoV-2 Delta variant prevalence reported by the CDC (gray dashed line). Error bars indicate 95% CI. Symbols shown above the red bars (January 2021 vaccinees) or purple bars (March 2021 vaccinees) indicate p values for weekly rates for those vaccinated with the Pfizer-BioNTech BNT162b2 vaccine being greater than weekly rates for those vaccinated with the Moderna mRNA-1273 vaccine. NS p ≥ 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001 by two-proportion Z-test.

Figure 5

COVID-19 Breakthrough Infection and Hospitalization Rates in Individuals Vaccinated in the January Group, and in the March Group by Age. (A)—Weekly infection rates per 100 K individuals vaccinated in the January 2021 and March 2021 vaccinee groups aged 65 to 74 (striped blue bars) vs. aged 75 to 84 (stippled blue bars) vs. aged 85 and older (solid blue bars). (B)—Weekly hospitalization rates per 100 K individuals vaccinated in January 2021 and March 2021 aged 65 to 74 (striped blue bars) vs. aged 75 to 84 (stippled blue bars) vs. aged 85 and older (solid blue bars). Weekly SARS-CoV-2 Delta variant prevalence reported by the CDC (gray dashed line). Error bars indicate 95% CI. Symbols shown above the bars indicate p values for weekly rates for the vaccinees aged 75 to 84 being greater than weekly rates for the vaccinees aged 65 to 74, p values for weekly rates for the vaccinees aged 85 and over being greater than weekly rates for the vaccinees aged 65 to 74, and p values for weekly rates for the vaccinees aged 85 and over being greater than weekly rates for the vaccinees aged 75 to 84. # p ≥ 0.05; × p < 0.05; ×× p < 0.01; ××× p < 0.001 by two-proportion Z-test (rate for 75 to 84 greater than rate for 65 to 74). NS p ≥ 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001 by two-proportion Z-test (rate for 85 and older greater than rate for 65 to 74). - p ≥ 0.05; + p < 0.05; ++ p < 0.01; +++ p < 0.001 by two-proportion Z-test (rate for 85 and older greater than rate for 75 to 84).

Figure 6

Predictor Variables for COVID-19 Breakthrough Case Hospitalization. Odds ratios determined by binary logistic regression analysis of confirmed COVID-19 breakthrough cases that required hospitalization for the disease and those that were managed with outpatient care only. The independent variables are on the left of the plot while the odds ratios values with 95% CI are on the right. Not shown: anticoagulant drugs (OR 1.20, 95% CI 1.12–1.29), opioid drugs (OR 1.20, 95% CI 1.11–1.30), antiplatelet drugs (OR 1.17, 95% CI 1.07–1.28), NSAID drugs (OR 1.14, 95% CI 1.03–1.27), Beta-2 agonist drugs (OR 1.12, 95% CI 1.02–1.23), ACE inhibitor drugs (OR 1.09, 95% CI 1.03–1.16), immunosuppressive drugs (OR 0.89, 95% CI 0.79–0.99), Azithromycin drugs (OR 0.88, 95% CI 0.77–1.00), or other ethnicities (OR 0.76, 95% CI 0.61–0.97). Multiunit housing variable: CDC SVI_EPL_MUNIT top quartile; High County Infection rate: beneficiary county of residence in the top quartile of U.S. county infection rate 14 days prior to COVID-19 diagnosis date.