First-in-Man: Case Report of Selective C-Reactive Protein Apheresis in a Patient with SARS-CoV-2 Infection

Jan Torzewski, Franz Heigl, Oliver Zimmermann, Florian Wagner, Christian Schumann, Reinhard Hettich, Christopher Bock, Stefan Kayser, Ahmed Sheriff, Jan Torzewski, Franz Heigl, Oliver Zimmermann, Florian Wagner, Christian Schumann, Reinhard Hettich, Christopher Bock, Stefan Kayser, Ahmed Sheriff

Abstract

BACKGROUND C-reactive protein (CRP) plasma levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel viral disease, are surprisingly high. Pulmonary inflammation with subsequent fibrosis in SARS-CoV-2 infection is strongly accelerated. Recently, we have developed CRP apheresis to selectively remove CRP from human plasma. CRP may contribute to organ failure and pulmonary fibrosis in SARS-CoV-2 infection by CRP-mediated complement and macrophage activation. CASE REPORT A 72-year-old male patient at high risk was referred with dyspnea and fever. Polymerase chain reaction analysis of throat smear revealed SARS-CoV-2 infection. CRP levels were ~200 mg/L. Two days after admission, CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started. CRP apheresis was performed via peripheral venous access on days 2, 3, 4, and 5. Following a 2-day interruption, it was done via central venous access on days 7 and 8. Three days after admission the patient was transferred to the intensive care unit and intubated due to respiratory failure. Plasma CRP levels decreased by ~50% with peripheral (processed blood plasma ≤6000 mL) and by ~75% with central venous access (processed blood plasma ≤8000 mL), respectively. No apheresis-associated side effects were observed. After the 2-day interruption in apheresis, CRP levels rapidly re-increased (>400 mg/L) and the patient developed laboratory signs of multi-organ failure. When CRP apheresis was restarted, CRP levels and creatinine kinases (CK/CK-MB) declined again. Serum creatinine remained constant. Unfortunately, the patient died of respiratory failure on day 9 after admission. CONCLUSIONS This is the first report on CRP apheresis in a SARS-CoV-2 patient. SARS-CoV-2 may cause multi-organ failure in part by inducing an excessive CRP-mediated autoimmune response of the ancient innate immune system.

Conflict of interest statement

Conflict of interest: Ahmed Sheriff is Founder and Shareholder of Pentracor GmbH. Christopher Bock and Stefan Kayser are employees of Pentracor GmbH

Conflicts of interest

Ahmed Sheriff is Founder and Shareholder of Pentracor GmbH. Christopher Bock and Stefan Kayser are employees of Pentracor GmbH.

Figures

Figure 1.
Figure 1.
Supine chest x-ray on days 1 (A), 3 (B), and 7 (C) showing progressive bilateral infiltrates, predominant basal distribution, and development of fibrosing alveolitis.
Figure 2.
Figure 2.
(A) CRP levels (reference range 0.00–5.00 mg/L) during the course of the patient’s hospital stay. CRP levels were highly elevated at admission and decreased with each CRP apheresis session. CRP apheresis sessions 1, 2, 3, and 4 (blue columns) used peripheral venous access (processed blood plasma ≤6000 mL) and sessions 5 and 6 (blue columns) used central venous access (processed blood plasma ≤8000 mL). (B) IL-6 and PCT levels during the course of the hospital stay. Both IL-6 and PCT increased with time, although the PCT increase was only moderate.
Figure 3.
Figure 3.
(A) CRP apheresis sessions (blue columns) and course of CK/CK-MB and LDH plasma levels. Interpretation see text. (B) CRP apheresis sessions (blue columns) and course of bilirubin and creatinine levels as well as international normalized ratio (INR). Marked CK/CK-MB increase occurred during the interruption of CRP apheresis and marked CK/CK-MB decrease occurred following CRP apheresis restart.
Figure 4.
Figure 4.
(A) CRP apheresis sessions (blue columns) and course of Horovitz quotient [17]. Respiratory failure with time. (B) CRP apheresis sessions (blue columns) and course of lactate. Respiratory failure with time.

References

    1. Du Clos TW. Pentraxins: Structure, function, and role in inflammation. ISRN Inflamm. 2013;2013:379040.
    1. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.
    1. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: A secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391:319–28.
    1. Sheriff A, Schindler R, Vogt B, et al. Selective apheresis of C-reactive protein: A new therapeutic option in myocardial infarction? J Clin Apher. 2015;30:15–21.
    1. Zimmermann O, Li K, Zaczkiewicz M, et al. C-reactive protein in human atherogenesis: facts and fiction. Mediators Inflamm. 2014;2014:561428.
    1. Kaplan MH, Volanakis JE. Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol. 1974;112:2135–47.
    1. Bharadwaj D, Stein MP, Volzer M, et al. The major receptor for C-reactive protein on leukocytes is Fcgamma receptor II. J Exp Med. 1999;190:585–90.
    1. Manolov DE, Rocker C, Hombach V, et al. Ultrasensitive confocal fluorescence microscopy of C-reactive protein interacting with FcgammaRIIa. Arterioscler Thromb Vasc Biol. 2004;24:2372–77.
    1. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: Implications for atherosclerosis. Circulation. 2001;103:1194–97.
    1. Slagman AC, Bock C, Abdel-Aty H, et al. Specific removal of C-reactive protein by apheresis in a porcine cardiac infarction model. Blood Purif. 2011;31:9–17.
    1. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in critically ill patients in the Seattle region – case series. N Engl J Med. 2020;382(21):2012–22.
    1. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395:1054–62.
    1. Zhang J, Litvinova M, Wang W, et al. Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: A descriptive and modelling study. Lancet Infect Dis. 2020 [Online ahead of print.
    1. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020 [Online ahead of print.
    1. Zhang R, Zhang YY, Huang XR, et al. C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II-induced hypertensive cardiac disease. Hypertension. 2010;55:953–60.
    1. Li JJ, Sanders RL, McAdam KP, et al. Impact of C-reactive protein (CRP) on surfactant function. J Trauma. 1989;29:1690–97.
    1. Ries W, Heigl F, Garlichs C, et al. Selective C-reactive protein-apheresis in patients. Ther Apher Dial. 2019;23:570–74.
    1. Ries W, Sheriff A, Heigl F, et al. “First in man”: Case report of selective C-reactive protein apheresis in a patient with acute ST segment elevation myocardial infarction. Case Rep Cardiol. 2018;2018:4767105.
    1. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: The Berlin Definition. JAMA. 2012;307:2526–33.
    1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315:801–10.
    1. Tillett WS, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of Pneumococcus. J Exp Med. 1930;52:561–71.
    1. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–48.

Source: PubMed

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