C-reactive protein and clinical outcomes in patients with COVID-19

Abstract

Background: A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19.

Methods and results: Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53-169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61-3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76-2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37-3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11-3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes.

Conclusions: Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.

Keywords: C-reactive protein; COVID-19; Coronavirus; Critical illness; Inflammation; Mortality.

Graphical abstract

Figure 1

Frequency distribution of initial CRP concentrations in patients hospitalized with COVID-19.

Figure 2

Mortality (A), critical illness (B), venous thrombo-embolism (C), and acute kidney injury (D) among patients with COVID-19, stratified by initial CRP measurement. Quartile 1: ≤53 mg/L. Quartile 2: >53 to ≤108 mg/L. Quartile 3: >108 to ≤169 mg/L. Quartile 4: >169 mg/L. Odds ratios adjusted for age, sex, race/ethnicity, body mass index, tobacco use, hypertension, hyperlipidaemia, chronic kidney disease, coronary artery disease, heart failure, and malignancy.

Figure 3

Associations between CRP and all-cause mortality, critical illness, venous thromb-oembolism, and acute kidney injury in subgroups by age, sex, race, and body mass index. Odds ratios adjusted for age, sex, race/ethnicity, body mass index, tobacco use, hypertension, hyperlipidaemia, chronic kidney disease, atrial fibrillation, coronary artery disease, heart failure, malignancy, initial ferritin, absolute lymphocyte count, D-dimer, and baseline use of statins, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and anticoagulants.

Figure 4

Associations between CRP and all-cause mortality, critical illness, venous thrombo-embolism, and acute kidney injury stratified by initial D-dimer measurement. The incidence (A) and adjusted odds (B) of adverse outcomes are shown. (low CRP <108 mg/dL; high CRP ≥108 mg/dL; low D-dimer ≤384 ng/mL; high D-dimer >384 ng/mL). (A) *P for trend <0.001 for all outcomes. (B) Odds ratios adjusted for age, sex, race/ethnicity, body mass index, tobacco use, hypertension, hyperlipidaemia, chronic kidney disease, atrial fibrillation, coronary artery disease, heart failure, malignancy, initial ferritin, absolute lymphocyte count, baseline use of statins, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,and anticoagulants.

Figure 5

Trajectory of CRP levels over time among patients with and without fatal disease (A), critical illness (B), VTE (C), and AKI (D).