Aggregate weekly numbers of COVID-19 cases and COVID-19–associated hospitalizations and deaths among persons aged ≥18 years with specimen collection dates during April 4–July 17, 2021, were analyzed by age group (18–49, 50–64, and ≥65 years) and vaccination status across 13 public health jurisdictions.* All participating jurisdictions had established processes for linking case surveillance and vaccination data from state/local immunization registries; this method usually assumes that cases among persons not matched to the registry are among unvaccinated persons. Eleven jurisdictions provided hospitalization data, and all submitted mortality data. Standard definitions were used for 1) COVID-19 cases,† 2) COVID-19 cases in fully vaccinated or not fully vaccinated persons,§ 3) COVID-19–associated hospitalizations,¶ and 4) COVID-19–associated deaths,** with specimen collection dates used as time points.
Two analysis periods, April 4–June 19 and June 20–July 17, were designated, based on weeks with <50% or ≥50% weighted prevalence of the SARS-CoV-2 Delta variant for the 13 jurisdictions.†† The percentages of total cases, hospitalizations, and deaths by vaccination status were calculated for each period and age group. The expected PVC was assessed using the formula: PVC = [PPV–(PPV*VE)]/[1–(PPV*VE)], where PPV is the proportion of the population vaccinated, or vaccination coverage (
1). PVC was calculated using VE estimates of 80%, 90%, and 95%. Vaccination coverage was estimated by age group using the sum of fully vaccinated persons divided by the 2019 U.S. intercensal population estimates.§§ Weekly age-specific incidences by vaccination status were calculated as the number of cases, hospitalizations, or deaths divided by the number of persons either fully vaccinated or not fully vaccinated (obtained by subtracting the number of fully vaccinated persons from total population estimates). Average weekly incidence in each period was age standardized using the 2000 U.S. Census standard population.¶¶ IRRs were calculated by dividing the incidence among persons not fully vaccinated by that among fully vaccinated persons; 95% CIs were calculated to account for variation in weekly rates. To aid interpretation of changes in IRRs, age-standardized crude VE was estimated as (1 – [incidence in vaccinated/incidence in unvaccinated]). A sensitivity analysis examined the impact of excluding partially vaccinated persons from IRRs using data available from nine jurisdictions. SAS (version 9.4; SAS Institute) and R (version 4.0.3; R Foundation) were used to conduct all analyses. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.***
During April 4–July 17, a total of 569,142 (92%) COVID-19 cases, 34,972 (92%) hospitalizations, and 6,132 (91%) COVID-19–associated deaths were reported among persons not fully vaccinated, and 46,312 (8%) cases, 2,976 (8%) hospitalizations, and 616 (9%) deaths were reported among fully vaccinated persons in the 13 jurisdictions (
Table). The weekly prevalence of the SARS-CoV-2 Delta variant increased from <1% to 90% during April 4–July 17. Full vaccination coverage increased from 19% to 54%; in the final week, coverage ranged by age group from 45% (in persons aged 18–49 years) to 73% (≥65 years).
During April 4–June 19, fully vaccinated persons accounted for 5% of cases, 7% of hospitalizations, and 8% of deaths overall; these percentages were higher during June 20–July 17 (18%, 14%, and 16%, respectively). Using the reported 37% vaccination coverage for the 13 jurisdictions during April 4–June 19 and an assumption of 90% VE, vaccinated persons would have been expected to account for 6% of cases (close to the 5% observed). With 53% coverage reported during June 20–July 17, vaccinated persons were expected to account for 10% of cases at a constant VE of 90%; the observed 18% would have been expected at a lower VE of 80%.
Averaged weekly, age-standardized rates (events per 100,000 persons) were higher among persons not fully vaccinated than among fully vaccinated persons for reported cases (112.3 versus 10.1), hospitalizations (9.1 versus 0.7), and deaths (1.6 versus 0.1) during April 4–June 19, as well as during June 20–July 17 (89.1 versus 19.4; 7.0 versus 0.7; 1.1 versus 0.1, respectively). Higher hospitalization and death rates were observed in older age groups, regardless of vaccination status, resulting in a larger impact of age-standardization on overall incidence for these outcomes.
Within each age group, the percentage of vaccinated persons among cases, hospitalizations, and deaths increased with increasing vaccination coverage (
Figure 1). As the prevalence of SARS-CoV-2 Delta variant surpassed 50%, the percentage of vaccinated persons among cases in each age group increased at rates corresponding to benchmarks for lower VE (i.e., from approximately 90% to <80%). Increases in the percentages of vaccinated persons aged ≥65 years among COVID-19–associated hospitalizations and deaths also appeared higher than expected. During June 20–July 17, age-standardized rates of cases, hospitalizations, and deaths among persons not fully vaccinated increased weekly; among fully vaccinated persons, case rates increased, but rates of hospitalizations and deaths remained largely unchanged (
Figure 2).
Age-standardized IRRs for cases in persons not fully vaccinated versus fully vaccinated decreased from 11.1 (95% CI = 7.8–15.8) during April 4–June 19 to 4.6 (95% CI = 2.5–8.5) during June 20–July 17, while IRRs decreased slightly from 13.3 (95% CI = 11.3–15.6) to 10.4 (95% CI = 8.1–13.3) for hospitalizations and from 16.6 (95% CI = 13.5–20.4) to 11.3 (95% CI = 9.1–13.9) for deaths during the same two periods. Persons aged ≥65 years had larger declines in IRRs for hospitalization and death than did younger age groups (Table). The change in age-standardized IRRs for cases between the April 4–June 19 and June 20–July 17 periods represented potential changes in crude VE from 91% to 78% for infection, from 92% to 90% for hospitalization, and from 94% to 91% for death (Supplementary Figure 1,
https://stacks.cdc.gov/view/cdc/109531). A sensitivity analysis excluding partially vaccinated persons in nine jurisdictions yielded similar trends but higher IRRs and VE estimates for hospitalizations and deaths (Supplementary Table,
https://stacks.cdc.gov/view/cdc/109533). Variability in IRRs was also observed among jurisdictions (Supplementary Figure 2,
https://stacks.cdc.gov/view/cdc/109532).
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Discussion
In 13 U.S. jurisdictions, rates of COVID-19 cases, hospitalizations, and deaths were substantially higher in persons not fully vaccinated compared with those in fully vaccinated persons, similar to findings in other reports (
2,
3). After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected for the given vaccination coverage and a constant VE. The IRR for cases among persons not fully vaccinated versus fully vaccinated decreased substantially; IRRs for hospitalizations and deaths changed less overall, but moderately among adults aged ≥65 years. Findings from this crude analysis of surveillance data are consistent with recent studies reporting decreased VE against confirmed infection but not hospitalization or death, during a period of Delta variant predominance and potential waning of vaccine-induced population immunity (
4–
6).†††
The findings in this report are subject to at least five limitations. First, combining unvaccinated and partially vaccinated persons resulted in lower IRR and VE estimates. Second, variable linkage of case surveillance, vaccination, hospitalization, and mortality data might have resulted in misclassifications that could influence IRR estimates; no substantial differences in ascertainment of outcomes by vaccination status were noted in jurisdictions that were able to assess this. Lags in reporting of deaths might have affected the second period differentially. Third, this was an ecological study in which IRRs lacked multivariable adjustments and causality could not be assessed (i.e., possible differences in testing or behaviors in vaccinated and unvaccinated persons). VE is being assessed through ongoing controlled studies. Fourth, the period when the SARS-CoV-2 Delta variant reached ≥50% overall prevalence was assumed to be the first week when most cases were infected with the Delta variant, but the week varied by jurisdiction. Finally, the data assessed from 13 jurisdictions accounted for 25% of the U.S. population, and therefore might not be generalizable.
Monitoring COVID-19 outcomes in populations over time by vaccination status is facilitated through reliable linkage of COVID-19 case surveillance and vaccination data. However, interpreting state-level variation by week might be challenging, especially for severe outcomes with small numbers. The framework used in this analysis allows for comparisons of observed IRRs and percentages of vaccinated cases, hospitalizations, and deaths to expected values. The data might be helpful in communicating the real-time impact of vaccines (e.g., persons not fully vaccinated having >10 times higher COVID-19 mortality risk) and guiding prevention strategies, such as vaccination and nonpharmacologic interventions.
FIGURE 1. Observed versus expected percentage of fully vaccinated persons among COVID-19 cases, hospitalizations, and deaths based on population vaccination coverage* and assumed 80%–95% vaccine effectiveness,† by week§ and age group — 13 U.S. jurisdictions,¶ April 4–July 17, 2021
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