Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19

Abstract

Background: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.

Objectives: This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients.

Methods: The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers.

Results: Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22).

Conclusions: Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.

Keywords: COVID-19; blood viscosity; cardiovascular disease; mortality; rheology epidemiology.

Graphical abstract

Figure 1

Flow Diagram of the Study Population Flow chart presenting study population. COVID-19 = coronavirus disease-2019.

Central Illustration

Effects of Blood Hyperviscosity on the Vascular System in COVID-19 Adjusted HRs (aHRs) calculated by Cox proportional hazards regression after adjustments for age; sex; hospital site; race; history of hypertension, diabetes mellitus, chronic kidney disease, and coronary artery disease; in-hospital statin use; anticoagulation therapy; date of admission; measure of initial oxygen support; and initial lab data (white blood cell count, C-reactive protein, and D-dimer). COVID-19 = coronavirus disease-2019.

Figure 2

Kaplan-Meier Curves for Hospitalized Patients With COVID-19 According to Estimated BV Kaplan-Meier curves for in-hospital mortality among patients with coronavirus disease-2019 (COVID-19) according to (A) estimated high-shear blood viscosity (BV) and (B) estimated low-shear BV.

Figure 3

Restricted Cubic Spline Showing Association Between eHSBV and In-Hospital Mortality (A) Restricted cubic spline showing association between estimated high-shear blood viscosity (eHSBV) and in-hospital mortality. (B) Histogram showing the distribution of eHSBV of the study participants. Models are adjusted for age; sex; hospital site; race; history of hypertension, diabetes, chronic kidney disease, and coronary artery disease; in-hospital statin use; anticoagulation therapy; date of admission; and measure of initial oxygen support. The solid line indicates HRs and shaded areas indicate 95% CIs. Four knots were placed at the 5th, 35th, 65th, and 95th percentiles of BV.

Figure 4

Association of eHSBV Mortality Patients According to Subgroups (A,B) Adjusted HRs calculated by Cox proportional hazards regression after adjustments for age; sex; hospital site; race; history of hypertension, diabetes, chronic kidney disease, and coronary artery disease; in-hospital statin use; anticoagulation therapy; date of admission; and measure of initial oxygen support. COVID-19 = coronavirus disease-2019; CRP = C-reactive protein; eHSBV = estimated high-shear blood viscosity.

Figure 4

Association of eHSBV Mortality Patients According to Subgroups (A,B) Adjusted HRs calculated by Cox proportional hazards regression after adjustments for age; sex; hospital site; race; history of hypertension, diabetes, chronic kidney disease, and coronary artery disease; in-hospital statin use; anticoagulation therapy; date of admission; and measure of initial oxygen support. COVID-19 = coronavirus disease-2019; CRP = C-reactive protein; eHSBV = estimated high-shear blood viscosity.