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, log e -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.