Targeting C-Reactive Protein by Selective Apheresis in Humans: Pros and Cons.

C-reactive protein (CRP), the prototype human acute phase protein, may be causally involved in various human diseases. As CRP has appeared much earlier in evolution than antibodies and nonetheless partly utilizes the same biological structures, it is likely that CRP has been the first antibody-like molecule in the evolution of the immune system. Like antibodies, CRP may cause autoimmune reactions in a variety of human pathologies. Consequently, therapeutic targeting of CRP may be of utmost interest in human medicine. Over the past two decades, however, pharmacological targeting of CRP has turned out to be extremely difficult. Currently, the easiest, most effective and clinically safest method to target CRP in humans may be the specific extracorporeal removal of CRP by selective apheresis. The latter has recently shown promising therapeutic effects, especially in acute myocardial infarction and COVID-19 pneumonia. This review summarizes the pros and cons of applying this novel technology to patients suffering from various diseases, with a focus on its use in cardiovascular medicine.

Targeting C-Reactive Protein by Selective Apheresis in Humans: Pros and Cons

C-reactive protein (CRP), the prototype human acute phase protein, may be causally involved in various human diseases. As CRP has appeared much earlier in evolution than antibodies and nonetheless partly utilizes the same biological structures, it is likely that CRP has been the first antibody-like molecule in the evolution of the immune system. Like antibodies, CRP may cause autoimmune reactions in a variety of human pathologies. Consequently, therapeutic targeting of CRP may be of utmost interest in human medicine. Over the past two decades, however, pharmacological targeting of CRP has turned out to be extremely difficult. Currently, the easiest, most effective and clinically safest method to target CRP in humans may be the specific extracorporeal removal of CRP by selective apheresis. The latter has recently shown promising therapeutic effects, especially in acute myocardial infarction and COVID-19 pneumonia. This review summarizes the pros and cons of applying this novel technology to patients suffering from various diseases, with a focus on its use in cardiovascular medicine.

Successful Treatment of a 39-Year-Old COVID-19 Patient with Respiratory Failure by Selective C-Reactive Protein Apheresis.

BACKGROUND High C-reactive protein (CRP) plasma levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with poor prognosis. CRP, by activating the classical complement pathway and interacting with macrophages via Fc gamma receptors, can cause pulmonary inflammation with subsequent fibrosis. Recently, we have reported first-in-man CRP apheresis in a "high-risk" COVID-19 patient. Treatment was unfortunately clinically unsuccessful. Here, we report on successful CRP apheresis treatment in a "lower-risk" COVID-19 patient with respiratory failure. CASE REPORT A 39-year-old male patient suffering from fatigue, dyspnea, and fever for 4 days was referred to us. The patient had to be intubated. Polymerase chain reaction (PCR) analysis of a throat smear revealed SARS-CoV-2 infection. Mutation analysis revealed the VOC B. 1.1.7 variant. CRP levels were 79.2 mg/L and increased to 161.63 mg/L. Procalcitonin (PCT) levels were continuously normal (<0.5 ng/ml). Antibiotic therapy was started to avoid bacterial superinfection. CRP apheresis was performed once via central venous access. CRP levels declined from a maximum of 161.63 mg/L to 32.58 mg/L. No apheresis-associated adverse effects were observed. Subsequently, CRP plasma levels declined day by day and normalized on day 5. The patient was extubated on day 5 and discharged from the Intensive Care Unit (ICU) on day 6. A second low CRP peak (maximum 22.41 mg/L) on day 7 remained clinically inapparent. The patient was discharged in good clinical condition with a CRP level of 6.94 mg/L on day 8. CONCLUSIONS SARS-CoV-2 infection can induce an uncontrolled CRP-mediated autoimmune response of ancient immunity. In this patient, the autoimmune response was potently and successfully suppressed by early selective CRP apheresis.

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

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.