Pre-pandemic leukocyte count is associated with severity of post-acute sequelae of SARS-CoV-2 infection among older women in the Women's Health Initiative

Objective Although dysregulated inflammation has been postulated as a biological mechanism associated with post-acute sequelae of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection (PASC) and shown to be a correlate and an outcome of PASC, it is unclear whether inflammatory markers can prospectively predict PASC risk. We examined the association of leukocyte count and high-sensitivity C-reactive protein (hsCRP) concentrations, measured ∼25 years prior to the coronavirus disease 2019 (COVID-19) pandemic, with PASC, PASC severity, and PASC-associated cognitive outcomes at follow-up among postmenopausal women. Methods Using biomarker data from blood specimens collected during pre-pandemic enrollment (1993-1998) and data on 1,237 Women's Health Initiative participants who completed a COVID-19 survey between June 2021 and February 2022, we constructed multivariable regression models that controlled for pertinent characteristics. PASC status was defined according to established World Health Organization criteria. Results Controlling for baseline characteristics, loge-transformed leukocyte count (β = 0.27; 95% confidence interval, 0.07-0.47, P = 0.009) and leukocyte count ≥5.5 × 1,000 cells/µL (β = 0.13; 95% confidence interval, 0.02-0.23; P = 0.02) were positively associated with PASC severity, defined as the sum of PASC symptoms, but not associated with overall PASC occurrence or PASC-related cognitive outcomes. Concentration of hsCRP, available on only ∼27% of participants, was not associated with any of the PASC outcomes, controlling for the same covariates. Conclusions Leukocyte count, a widely available clinical marker of systemic inflammation, is an independent predictor of PASC severity in postmenopausal women. Heightened inflammation preceding SARS-CoV-2 infection may contribute to PASC development. Limited statistical power to assess hsCRP role warrants further study.