C‐reactive protein as an effector molecule in Covid‐19 pathogenesis

Abstract

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19.From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials. K E Y W O R D SC-reactive protein, COVID-19, SARS-CoV-2, severe evolution | INTRODUCTIONSARS-CoV-2 starts its pathogenetic process through reninangiotensin system (RAS) activation, binding to the angiotensin II converting enzyme (ACE2) and originating a series of proinflammatory events that can induce a cytokine storm. 1,2 The C-reactive protein (CRP) is a molecule produced by the interaction of SARS-CoV-2 with ACE2, 3-5 which is not only an indicator of acute phase of inflammation but also has been related to prognosis and severity of Covid-19. [5][6][7] Therefore, CRP can be an important factor in the cellular damage during Covid-19. This review aims to describe the different mechanisms by which SARS-CoV-2 can induce cell

Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…Increased CRP levels have been described in patients infected with the most virulent types of influenza A virus, and the outcome of human influenza disease has been related to increased CRP production, with the highest levels of CRP corresponding to the more severe symptoms including mortality (197)(198)(199)(200)(201). Similarly, high levels of CRP were found in patients with severe COVID-19 disease showing increased organ damage, worse outcome, and increased mortality (202)(203)(204)(205)(206). The hyperinflammation associated with COVID-19 infection in children and adults (207)(208)(209)(210) affects all organs and tissues including atherosclerotic lesions (Figure 7) and is always associated with very high levels of CRP, that enhance and amplify the infl ammatory and prothrombotic microenvironment, most certainly mediated by increased generation of mCRP, which could also contribute to plaque instability through the demonstrated CRP-induced expression of matrix metalloproteinases 1, 2, and 9 (154).…”

“…The hyperinflammation associated with COVID-19 infection in children and adults (207)(208)(209)(210) affects all organs and tissues including atherosclerotic lesions (Figure 7) and is always associated with very high levels of CRP, that enhance and amplify the infl ammatory and prothrombotic microenvironment, most certainly mediated by increased generation of mCRP, which could also contribute to plaque instability through the demonstrated CRP-induced expression of matrix metalloproteinases 1, 2, and 9 (154). Considering the pathophysiology of COVID-19 infection and its complications, it is appealing to propose that membrane-associated monomeric CRP isoform may play a role, particularly promoting proinflammatory and procoagulant effects (205,206). Viruses utilize host cells to reproduce and viral infections eventually result in cell death, caused by cell's surface membrane alterations, apoptosis, and cell lysis (211,212).…”

Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase

“…The opsonization of affected endogenous cells significantly contributes to the enlargement of organ damage ( 19 ). In the case of progressive, severe COVID-19 with high CRP plasma concentrations, pulmonary tissue is irreversibly disposed by the action of CRP ( 20 ).…”

SARS-CoV-2 and the Host Cell: A Tale of Interactions

“…Interleukin 6, interleukin 8, E-cadherin, MCP-1, VEGF, among other molecules, are involved in the cytokine release syndrome aggravated by trans signaling [reviewed in (21)], similarly to what has been observed in the case of SARS-CoV (22). These proinflammatory mediators can, in turn, perpetuate lung disease by elevating C-reactive protein from the liver through STAT3-IL-6 signaling (23), contributing to lung tissue damage.…”