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1.
Am J Case Rep ; 22: e932964, 2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1344550

ABSTRACT

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.


Subject(s)
Blood Component Removal , COVID-19 , Respiratory Insufficiency , Adult , C-Reactive Protein , Humans , Male , SARS-CoV-2
2.
Nat Commun ; 12(1): 1726, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1142436

ABSTRACT

SARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2/drug effects , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors/pharmacology , alpha 1-Antitrypsin/pharmacology , Antibodies, Viral/blood , Antiviral Agents/pharmacology , COVID-19/blood , Caco-2 Cells , Humans , Immunoglobulin G/blood , Molecular Docking Simulation , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , Virus Replication/drug effects
3.
Am J Case Rep ; 21: e925020, 2020 Jul 14.
Article in English | MEDLINE | ID: covidwho-652210

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.


Subject(s)
Betacoronavirus , Blood Component Removal/methods , C-Reactive Protein/metabolism , Coronavirus Infections/therapy , Multiple Organ Failure/therapy , Pneumonia, Viral/therapy , Aged , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Humans , Male , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , SARS-CoV-2
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