Associations between CRP concentration and adverse outcomes were consistent in subgroups defined by age, sex, race, and obesity 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. In a subgroup analyses by D-dimer level, patients with low values of both CRP and D-dimer were at low risk for in-hospital adverse events.
In contrast, the incidences of VTE While both CRP and D-dimer increased the adjusted odds of an adverse outcome, patients with elevation of both CRP and D-dimer concentrations had the greatest risk of adverse events Figure 4 B.
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. Levels of CRP were significantly higher over time in patients who developed AKI, critical illness, or who died during hospitalization. Patients with elevated CRP concentrations above the median value at the time of initial presentation were more likely to have VTE, AKI, critical illness, and in-hospital mortality during the subsequent hospital stay than those with lower initial measurements, and patients with the highest CRP values had the worst clinical outcomes.
C-reactive protein is well established as a marker of systemic inflammation and severe infection. As an acute-phase reactant, CRP binds to phosphocholine in pathogens and membranes of host cells, and acts as an opsonin to enhance phagocytosis and facilitate clearance.
Ligand-bound CRP also efficiently activates the classical pathway of the complement system, an important component of innate host defence. In our cohort, IL-6 was independently associated with adverse outcomes in patients with high and low initial CRP concentrations.
Ultimately, CRP may be preferred as a biomarker since it is inexpensive and widely available at most medical centres, facilitating rapid implementation of routine biomarker measurement into clinical care of patients with COVID In contrast to CRP measurement for cardiovascular risk stratification, in which inflammation may contribute to accelerated atherosclerosis and instability of atherosclerotic plaque, CRP concentrations in COVID infection reflect disease severity and the magnitude of the acute inflammatory response.
The role of systemic inflammation in the pathogenesis of COVID remains incompletely understood, and causal relationships between inflammation measured by CRP and adverse clinical outcomes are speculative. However, the detrimental inflammatory response observed in some individuals with COVID parallels secondary haemophagocytic lymphohistiocytosis also known as macrophage activation syndrome , and may independently contribute to multiorgan damage in COVID The clinical benefit of immunosuppression further supports the hypothesis that inflammation in response to viral infection contributes to poor outcomes in COVID However, patients were at highest risk when they presented with concomitant elevations in CRP and D-dimer concentrations, providing additional support for the synergistic role of inflammation and thrombosis in the pathogenesis of disease associated with SARS-CoV-2 infection.
Limitations of this study include its retrospective observational study design. The first measured CRP concentration at hospital admission was used for the primary analyses. Patients were hospitalized at a single healthcare system in New York during a 6-week period of rapid viral spread, although a diverse cohort of COVID patients across four inpatient sites is represented.
The time period studied preceded the finding that immunosuppression improves clinical outcomes in patients with severe COVID, 26 and steroids were administered at the discretion of the treating providers. Knowledge of the initial CRP concentration by the admitting physician may have altered subsequent patient care and could confound outcomes.
Although data on steroid use were not available, few patients were likely to receive steroids prior to the initial CRP measurement during hospitalization.
In some cases, steroids or tocilizumab, an IL-6 inhibitor, were administered to critically ill patients. However, the timing of drug administration, duration of use, and dosing of these agents were not recorded in this dataset. Venous thrombo-embolism was determined according to treating physicians based on available clinical imaging and laboratory data, and were not independently adjudicated. Finally, only in-hospital outcomes were recorded, and associations between CRP and long-term outcomes following discharge could not be determined.
Inflammatory biomarker-based approaches to risk stratification and treatment should be evaluated to improve outcomes of patients with SARS-CoV-2 infection. Supplementary material is available at European Heart Journal online. Conflict of interest: J. The remaining authors have no disclosures to report. National Center for Biotechnology Information , U. Eur Heart J. Published online Jan Nathaniel R Smilowitz 1 Leon H.
Michael Garshick 1 Leon H. Binita Shah 1 Leon H. Judith S Hochman 1 Leon H. Jeffrey S Berger 1 Leon H. Author information Article notes Copyright and License information Disclaimer. Nathaniel R Smilowitz and Dennis Kunichoff authors contributed equally to this work.
Corresponding author. Copyright Published on behalf of the European Society of Cardiology. All rights reserved. This article has been cited by other articles in PMC.
Introduction In the mid s, immunoassays for C-reactive protein CRP , with greater sensitivity than those previously in routine use, revealed that increased CRP values, even within the range previously considered normal, strongly predict future coronary events. The acute-phase response CRP, named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae , was the first acute-phase protein to be described and is an exquisitely sensitive systemic marker of inflammation and tissue damage 1.
Table 1 Changes in concentrations of plasma proteins in the acute-phase response. Open in a separate window. Table 2 CRP responses in disease. Table 3 Routine clinical uses of CRP measurement. Structure and phylogeny of CRP CRP belongs to the pentraxin family of calcium-dependent ligand-binding plasma proteins, the other member of which in humans is serum amyloid P component SAP. Figure 1. Ligand binding and biological role of CRP Human CRP binds with highest affinity to phosphocholine residues, but it also binds to a variety of other autologous and extrinsic ligands, and it aggregates or precipitates the cellular, particulate, or molecular structures bearing these ligands.
CRP and cardiovascular disease Earlier work suggested a prognostic association between increased CRP production and outcome after acute myocardial infarction 20 and in acute coronary syndromes CRP and pathogenesis of atherosclerosis? CRP and myocardial infarction Tissue necrosis is a potent acute-phase stimulus, and, following myocardial infarction, there is a major CRP response, the magnitude of which reflects the extent of myocardial necrosis CRP: a target for therapy in human disease?
Acknowledgments G. Footnotes Conflict of interest: The authors have declared that no conflict of interest exists. References 1. Acute phase proteins with special reference to C-reactive protein and related proteins pentaxins and serum amyloid A protein. Solid phase radioimmunoassays for C-reactive protein. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. Hutchinson WL, et al.
Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Genes Immun. The physiological structure of human C-reactive protein and its complex with phosphocholine. Comparative studies on the binding properties of human and rabbit C-reactive proteins. Isolation and characterisation of C-reactive protein and serum amyloid P component in the rat. Baltz ML, et al. Phylogenetic aspects of C-reactive protein and related proteins.
C-reactive protein: binding to lipids and lipoproteins. Interaction of C-reactive protein with artificial phosphatidylcholine bilayers. Du Clos TW. C-reactive protein reacts with the U1 small nuclear ribonucleoprotein. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity.
Volanakis JE. Complement activation by C-reactive protein complexes. Regulation of complement activation by C-reactive protein. Bickerstaff MCM, et al. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity.
Harnett W, Harnett MM. Phosphorylcholine: friend or foe of the immune system? Kushner I, Kaplan MH. Studies of acute phase protein. An immunohistochemical method for the localization of Cx-reactive protein in rabbits.
Association with necrosis in local inflammatory lesions. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids.
Measurement of serum C-reactive protein concentration in myocardial ischaemia and infarction. Heart J. Liuzzo G, et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Tracy RP, et al.
C-reactive protein and incidence of cardiovascular disease in older women: the rural health promotion project and the cardiovascular health study. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. Koenig W, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA Monitoring Trends and Determinants in Cardiovascular Disease Augsburg Cohort Study, to Danesh J, et al.
Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease.
Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Association between C-reactive protein and features of the metabolic syndrome: a population-based study.
Diabetes Care. Chambers JC, et al. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites.
Ford ES. Body mass index, diabetes, and C-reactive protein among U. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction.
A potential role for cytokines originating from adipose tissue? Freeman DJ, et al. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. McLaughlin T, et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Oral contraceptive use is associated with a systemic acute phase response. Fibrinolysis and Proteolysis.
Cushman M, et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Does exercise reduce inflammation? Psychiatry, , 60 12 , The [39] Misiak, B. Samochowiec, J. Cytokines and C-reactive protein Neuropsychiatr. Associations of high sensitivity C- [24] Gejman, P. The role of genetics in reactive protein levels in schizophrenia and comparison groups the etiology of schizophrenia.
North Am. Relationship of C- S. Integration of DNA sequence and DNA methylation changes reactive protein to risk of cardiovascular disease in the elderly.
Re- in monozygotic twin pairs discordant for schizophrenia. Promotion Project. Epigenetic regulation in human brain- ] focus on histone lysine methylation. Psychiatry, , 65 3 , [42] Cesari, M. Circula- in individuals with schizophrenia. Schizophr Res. The association of C- X. Stroke, , 36 10 , Boerwinkle, E. Population-based study of high plasma C-reactive crovascular pathology in Asian populations from Singapore?
PLoS protein concentrations among the Inuit of Nunavik. Circum- One, , 8 7 , e Reviews of Interventions. Cochrane Book Series. Wiley-Blackwell, Observational and mechanistic links between C-reactive protein Maturitas, , 89, Diabetes, hyperglycemia, tions: explanation and elaboration.
BMJ, , , b Diabetes Care, , 29 8 , Elevated serum levels of C-reactive protein are [47] Panickar, K. The beneficial role of anti- associated with more severe psychopathology in a subgroup of pa- inflammatory dietary ingredients in attenuating markers of chronic tients with schizophrenia. Aging and low-grade in Arab schizophrenic patients. Age Dordr. C-reactive protein doi. Serum hs- to patients with schizophrenia.
Eur Neurol. Genetic vari- [50] Song, I. Relationship ants of the inflammatory C-reactive protein and schizophrenia in between the hs-CRP as non-specific biomarker and Alzheimer's Armenian population: a pilot study. The inflammatory markers S. Elevated C-reactive protein and cognitive deficits in CRP, IL-6, and IL are associated with cognitive function--data individuals with bipolar disorder.
Aging, , 38, Psychiatry, , 5 2 , EE Interleukin-6 and C-reactive pro- [68] Khandaker, G. A popula- tein, successful aging, and mortality: the PolSenior study. C-reactive protein levels Re- [69] Wium-Andersen, M. Elevated lat. Inflammation and schizo- phrenia in the general population: a prospective study. Expert Rev. Inflammatory markers in antipsy- [71] Dickerson, F. In- nondeficit features. Psych Research. Schizophr Bull, , 42 1 , Quality of pairment but not of psychiatric symptoms in individuals with life is associated with chronic inflammation in schizophrenia: a schizophrenia.
Additive effects of elevated C-reactive protein and P. JAMA Psychiatry, , birth cohort study. Brain Behav. High levels of vitamin D in relation to re- Yasukawa, A. Psy- sanishi, S. Hayakawa, T. Correla- [75] Barzilay, R. Elevated C-reactive protein levels in schizophrenia inpa- in psychiatric inpatients: A cross-sectional study.
Acta, tients is associated with aggressive behavior. Psychiatry, , , Elevated copper, hs C-reactive protein and dyslipidemia in drug L.
Increased ratio of free schizophrenia: Relation with psychopathology score. Asian J. Psy- Transcriptome se- Psychia- [90] Dickerson, F. Elevated C-reactive protein and cognitive deficits in [PMID: ] individuals with bipolar disorder.
A significant causal association between C-reactive Djurovic, S. Elevated C-reactive protein is associated with sensory gating potential confounders. Psychiatry Clin. Serum high- rieux, C. Chronic pe- sensitivity C-reactive protein: A delicate sentinel elevated in drug- ripheral inflammation is associated with cognitive impairment in free acutely agitated patients with schizophrenia.
Physical functional H. The serum level of C-reactive pro- capacity and C-reactive protein in schizophrenia. Psychiatry, tein CRP is associated with cognitive performance in acute phase , 7, BMC Psychiatry, , 16, Serum-soluble interleukin-2 receptors Severance, E. Infection in neuroleptic-naive schizophrenic subjects and in medicated and inflammation in schizophrenia and bipolar dis-order.
Acta Res. An integrative view. Psychiatry Lang, A. Inflammatory, cardio- Res. C- Taylor, D. Minimising metabolic and cardio- reactive protein and white blood cell levels in schizophrenia, bipo- vascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.
Oxford , , 21 4 , Psychiatry, , doi. Hospital admission with infec- [87] Metcalf, S. Signaling to NF-kappaB. Genes Dev. Psychiatry, , 70 7 , [PMID: ] Oxidative stress in schizophrenia: an ] integrated approach.
Peripheral interleukin-2 level is associated with nega- [] Furukawa, H. Interleukin-1, but not stress, stimulates glucocorticoid output dur- Physiol. C-reactive protein is elevated in schizo- [] Sparkman, N. Neuroinflammation associated phrenia. Atypical antipsychotics suppress production of proinflammatory [] Khandaker, G. Prenatal cytokines and up-regulate interleukin in lipopolysaccharide- maternal infection, neurodevelopment and adult schizophrenia: a treated mice.
Psychiatry, systematic review of population-based studies. Prenatal infection and schizophrenia: a Fernandes, B. Psychia- Kapczinski, F. Ele- [] Emiliani, F. Oxidative stress and vated maternal C-reactive protein and increased risk of schizophre- schizophrenia: recent breakthroughs from an old story. Psychiatry, , 9 , Psychiatry, , 27 3 , Neuroinflam- [] Meyer, U.
Inflammatory processes in mation and oxidative stress in psychosis and psychosis risk. Neural basis of psychosis-related behaviour nard, T. Brain Res. Oxidative stress-driven parvalbumin in- 2 , Psychiatry, , 22 7 , Schizophrenia and viral infection during neurodevel- doi. Psychiatry, , 6 6 , [] Hoftman, G. Layer 3 excitatory and Psychiatry, , R. Serologic evidence 81 10 , Psychiatry, , 61 8 ,
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