SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World SettingFREE

In response to the SARS-CoV-2 pandemic, the VA rapidly created a national VA COVID-19 Shared Data Resource. Using case definitions and data mapping, which were validated collaboratively across the VA, the resource contains information on all veterans with a confirmed laboratory diagnosis of SARS-CoV-2 infection within the VA and those who were tested outside the VA with a VA clinical note confirming the diagnosis. The VA COVID-19 Shared Data Resource is updated regularly and contains extensive demographic, clinical, pharmacologic, laboratory, vital sign, and clinical outcome information derived from multiple validated sources, including the VA Corporate Data Warehouse and the VA electronic medical record.

For the current study, we identified all veterans in the VA COVID-19 Shared Data Resource who had SARS-CoV-2 testing between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020. For each person who tested positive, we identified a propensity score–matched control participant who tested negative, matched by age, sex, race, body mass index, Charlson Comorbidity Index score, and geographic location. We used nearest-neighbor matching with a caliper of 0.25 SD. The Charlson Comorbidity Index is a validated and widely used score that identifies persons at the highest risk for mortality over a period of time based on the presence and severity of comorbidities (12–14). For geographic location, we used the VA facility where the index test was performed to account for geographic variation in disease incidence and testing patterns. Data retrieved included demographic characteristics, clinical diagnoses, presence of symptoms at presentation, anthropometric measurements and vital signs, all pharmacologic interventions, and select laboratory results. Data on vaccine administration date and the type of vaccine used were also retrieved. Comorbidities were defined according to the definitions used in the VA Corporate Data Warehouse, which uses the International Classification of Diseases (Ninth or 10th Revision, as appropriate) for classifying comorbidities. Baseline diagnoses included all diagnoses recorded in the 2 years before the index date.

We used a test-negative case–control design to evaluate the effectiveness of vaccination against confirmed SARS-CoV-2 infection. This is a widely accepted design for determining vaccine effectiveness in a population after the introduction of a vaccine (15–17). We used conditional logistic regression to calculate the odds of testing positive among the vaccinated group versus the unvaccinated group (18, 19). Vaccine effectiveness was calculated by using the following formula:

1 − Odds(T+|Vaccinated) / Odds(T+|Nonvaccinated)

Our primary outcome of interest was overall vaccine effectiveness 7 or more days after the second dose. We also assessed vaccine effectiveness among those who received only 1 dose and effectiveness anytime after receipt of the second dose. We evaluated effectiveness separately among those who received the Pfizer–BioNTech BNT-162b2 vaccine and those who received the Moderna mRNA-1273 vaccine.

Finally, we performed subgroup analyses by age group, sex, race, and comorbidity burden to determine vaccine effectiveness in various population subgroups. Effectiveness was calculated for each subgroup, and P values were calculated to test the significance of the difference within each subgroup. A P value less than 0.05 was considered significant. For all point estimates of vaccine effectiveness, we calculated 95% CIs (19, 20).

The study was approved by the Institutional Review Board at the VA Pittsburgh Healthcare System. A waiver of informed consent was granted for the study.

There was no external funding source for this study.