Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data

Abstract

Objectives: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. Design: Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. Setting: Veterans Health Administration (VHA) medical centers. Participants: Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. Intervention: mRNA vaccination. Measurements: New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0–<0.1), pre-frail (≥0.1–<0.21) and frail (≥0.21). Results: A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45–72; 87.5%men; 68.1%white; 1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8–65.7), versus prefrail 73.9%(95%CI:72.0–75.7), and robust, 77.0 %(95%CI:75.7–78.3). Conclusions: This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines.