PB1370 - Circulating C-reactive protein and D-dimer concentrations and risk of Severe Covid-19: the Collaborative Cohort of Cohorts for Covid-19 Research (C4R)

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Mary Cushman, MD, MSc

Professor
Department of Medicine, Larner College of Medicine at the University of Vermont, USA
Colchester, Vermont, United States

Co-Author(s)

YC

Yuni Choi

Biostatistician
Columbia University
New York, New York, United States
DJ

David Jacobs

Professor
University of Minnesota
Minneapolis, Minnesota, United States
AR

Alexander Reiner

Professor
University of Washington
Seattle, Washington, United States
RD

Ryan T. Demmer

Professor
Mayo Clinic
Rochester, Minnesota, United States
RT

Russell P. Tracy

University Distinguished Professor
University of Vermont
Burlington, Vermont, United States
NO

Nels C. Olson

Assistant Professor
University of Vermont
Burlington, Vermont, United States
MD

Margaret F. Doyle

Associate Professor
University of Vermont
Burlington, Vermont, United States
DK

Debora Kamin Mukaz

Assistant Professor
University of Vermont
Burlington, Vermont, United States
LR

Laura M. Raffield

Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
YM

Yuan-I Min

Associate Professor
University of Mississippi
Jackson, Mississippi, United States
RV

Ramachandran S. Vasan

Professor
University of Texas Southwestern
Dallas, Texas, United States
VX

Vanessa Xanthakis

Associate Professor
Boston University
Boston, Massachusetts, United States
Andrew D. Johnson, PhD

NHLBI, Massachusetts, United States
BM

Barry Make

Professor
National Jewish Health
Denver, Colorado, United States
ER

Elizabeth Regan

Associate Professor
National Jewish Health
Denver, Colorado, United States
RB

Russell Bowler

Professor
National Jewish Health
Denver, Colorado, United States
EO

Elizabeth C. Oelsner

Assistant Professor
Columbia University
New York, New York, United States

Background: Thromboinflammation is a hallmark of Covid-19. During infection higher C-reactive protein (CRP) and D-dimer predict adverse outcomes. We hypothesized higher pre-pandemic CRP and D-dimer, reflecting a higher thromboinflammatory setpoint, might identify people at greater risk of severe manifestations of Covid-19.

Aims: Determine the association of pre-pandemic CRP and D-dimer with risk of hospitalized or fatal (hereafter, “severe”) Covid-19 in a multi-ethnic US general population sample.

Methods: C4R harmonized pre-pandemic measures and ascertained Covid-19 across 14 longstanding cohort studies from 2020-2023. This investigation included 5 cohorts (see table) with pre-pandemic CRP or D-dimer data. Participants provided informed consent per associated ethics committees. Hazard ratios of severe Covid-19 by pre-pandemic biomarkers were estimated using Fine-Gray subdistribution hazards models, treating non-severe Covid-19 as a competing risk, and adjusting for pre-pandemic sociodemographic and clinical characteristics.

Results: CRP was available in 18,336 participants and D-dimer in 13,379; these were measured on average 20y before the pandemic. Mean age at the start of the pandemic was 76 years, the most represented race or ethnic groups were White (55.5%) and Black (38.5%). Of 2,294 Covid-19 cases, 402 were severe and 1,892 non-severe. The incidence of severe Covid-19 rose monotonically across CRP but not D-dimer categories (Figure & Table). Adjusting for demographics higher CRP doubled the risk of severe Covid-19, with modest attenuation with further adjustment. This association did not differ by age or BMI (p >0.05). There was no association for D-dimer.

Conclusion(s): In this older age multi-ethnic population, higher CRP in middle age was associated with greater risk of severe Covid-19. Since we considered non-severe Covid-19 as a competing risk, CRP may reflect factors related to progression to more serious Covid-19 illness. While Covid-19 causes coagulopathy, higher pre-pandemic coagulation activation (higher D-dimer) was not associated with severe disease.
Funded by: US National Institutes of Health