Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves

Abstract

Background: Older populations have suffered the highest rates of SARS-CoV-2 infection and associated complications, including Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Frailty is a geriatric syndrome that often coexists with COVID-19 infection. The vulnerability to stressors caused by multisystemic dysfunction that characterizes frailty may predispose older adults to develop PASC. Methods: Retrospective cohort study using the VA COVID-19 Shared Data Resource to identify US veterans testing positive for SARS-CoV-2 between July 2021 and February 2022, without prior positive tests and who were alive 30 days after infection. Frailty was calculated using a 31-item VA Frailty Index generated from electronic health records. We categorized Veterans into robust (FI ≤ 0.10), prefrail (FI: >0.10- < 0.21), and frail (FI ≥ 0.21). We assessed the association between frailty and PASC and vaccination and PASC using Cox survival model, adjusting for covariates. Results: We identified 245,857 COVID-19-positive veterans surviving 30 days after infection. The mean age was 57.5 ± 16.5 years; 87.2% were males, 68.1% were white, and 9.0% were Hispanic. Almost half of the sample (48.9%) were classified as robust, while 28.3% were pre-frail and 22.7% were frail; 99,886 (40.6%) were fully vaccinated, and 33,516 (13.6%) received booster doses. Over a median follow-up of 143 days (IQR = 101), 23,890 (9.7%) patients developed PASC. Within 6 months after infection, frailty and pre-frailty were associated with a 41% (adjusted HR [aHR]:1.40 (95% CI: 1.35–1.47) and 15% (aHR: 1.17 (95% CI: 1.11–1.19) increase in the risk of PASC compared with the robust, respectively. Vaccination and booster doses before infection were associated with a 27% (aHR: 0.73 (95% CI: 0.71–0.75) and 33% (aHR: 0.66 (95% CI: 0.63–0.69) reduction in the risk of developing PASC, respectively. Conclusions: Frailty was associated with an increased risk of developing PASC. Vaccination was associated with a decreased risk of PASC, further reduced by booster doses. Early recognition of frailty in patients with COVID-19 may assist in the early identification and management of PASC.