Abstract Body: Background: Thrombo-inflammation is a hallmark of acute Covid-19, with higher thrombo-inflammatory markers during infection associated with adverse outcomes. We hypothesized that higher pre-pandemic biomarkers, reflecting a higher thrombo-inflammatory setpoint, might identify people at greater risk of severe manifestations of Covid-19.

Hypothesis: Pre-pandemic inflammation markers are associated with risk of hospitalized or fatal (hereafter, “severe”) Covid-19 in a multi-ethnic US sample.

Methods: From 2020-2023, C4R harmonized pre-pandemic measures and ascertained Covid-19 across 14 longstanding cohort studies. In 12 cohorts, we assessed biomarker data and covariates from the study visit closest to the pandemic for 6 analytes shown in the Table. HRs of severe Covid-19 by pre-pandemic biomarkers were estimated using cause-specific Cox regression, treating non-severe Covid-19 as a competing risk, and adjusting for pre-pandemic sociodemographic and clinical characteristics.

Results: Biomarkers were measured a mean of 20 years before the pandemic with different sample sizes for each (Table footnote). Mean age at the start of the pandemic was in the 60s or 70s depending on the biomarker. The most represented race or ethnic groups were White and Black. The largest sample was for C-reactive protein, and there were 1,001 severe Covid-19 cases among 38,784 participants. In the adjusted models, considered individually, higher CRP, leukocyte count, factor VIII and fibrinogen, but not other markers, were associated with greater risk of severe Covid-19 (Table).Associations were robust across subgroups and time since biomarker measurement (example for C-reactive protein in Figure).

Conclusions: In this prospective multi-study analysis of a multi-ethnic population, higher basal levels of thrombo-inflammation markers were associated with greater risk of severe Covid-19. Since we considered non-severe Covid-19 as a competing risk, associations may reflect factors related to progression to more serious Covid-19 illness.