The role of the complement, contact and coagulation systems network in COVID-19

Title [en]

Abstract [sv]

Background:COVID-19 is caused by SARS cov2, a Corona virus that was first reported 31st of Dec 2019 in the Chinese city of Wuhan. It causes in most cases a mild to medium severe influenza-like disease with sore throat, fever and a dry cough. In a few cases, though, the disease retakes after 9-10 days and develops into a respiratory distress syndrome (RDS), which in a few cases may need intensive care with ventilator support. About 20% of these patients succumb due to pulmonary dysfunction. In the RDS stage the patient has a fever, dry cough, low grade oxygen saturation, increased risk of thromboembolism, and severe CT alterations in the periphery of the lungs resembling acute RDS (ARDS). The cause of this COVID-19 RDS disease is not known.Aim:Taken together with the obvious coagulation activation (thromboembolism), we hypothesize that COVID-19 RDS is caused by the humoral innate immune system (HIIS) involving at least the contact-, complement-, coagulation- and the angiotensin- systems. The aim of this application is to find evidence that these systems are activated in COVID-19, in order to support giving already licensed therapeutic inhibitors of these systems to patients with COVID-19 RDS.Work plan:1. Screen COVID-19 RDS patients longitudinally over time for contact (kallikrein/kinin)-, complement-, and coagulation-system biomarkers.2. Analyze COVID-19 RDS patients with capillary electrophoresis/blotting (WES) for evidence of contact (kallikrein/kinin)-, complement-, and coagulation-system activation.3. Analyze COVID-19 RDS patients cross sectionally with selected biomarkers from WP1 and 2 and correlate the results with clinical data and routine laboratory results.4. Analyze COVID-19 RDS patients from Milan treated with the complement inhibitor AMY-101 longitudinally over time.Significance:The preliminary data from our laboratory also implicates that the contact system is activated suggesting that the whole blood cascade system is engaged and that particularly the complement system and to some degree the coagulation system, seems to be a prognostic factor that can be used immediately in the clinic. If we together with our colleagues in Milan and Philadelphia also can show that complement inhibition with AMY-101 is beneficial for the patients, a new treatment for COVID-19 patients can be developed.

Abstract [en]

Background:COVID-19 is caused by SARS cov2, a Corona virus that was first reported 31st of Dec 2019 in the Chinese city of Wuhan. It causes in most cases a mild to medium severe influenza-like disease with sore throat, fever and a dry cough. In a few cases, though, the disease retakes after 9-10 days and develops into a respiratory distress syndrome (RDS), which in a few cases may need intensive care with ventilator support. About 20% of these patients succumb due to pulmonary dysfunction. In the RDS stage the patient has a fever, dry cough, low grade oxygen saturation, increased risk of thromboembolism, and severe CT alterations in the periphery of the lungs resembling acute RDS (ARDS). The cause of this COVID-19 RDS disease is not known.Aim:Taken together with the obvious coagulation activation (thromboembolism), we hypothesize that COVID-19 RDS is caused by the humoral innate immune system (HIIS) involving at least the contact-, complement-, coagulation- and the angiotensin- systems. The aim of this application is to find evidence that these systems are activated in COVID-19, in order to support giving already licensed therapeutic inhibitors of these systems to patients with COVID-19 RDS.Work plan:1. Screen COVID-19 RDS patients longitudinally over time for contact (kallikrein/kinin)-, complement-, and coagulation-system biomarkers.2. Analyze COVID-19 RDS patients with capillary electrophoresis/blotting (WES) for evidence of contact (kallikrein/kinin)-, complement-, and coagulation-system activation.3. Analyze COVID-19 RDS patients cross sectionally with selected biomarkers from WP1 and 2 and correlate the results with clinical data and routine laboratory results.4. Analyze COVID-19 RDS patients from Milan treated with the complement inhibitor AMY-101 longitudinally over time.Significance:The preliminary data from our laboratory also implicates that the contact system is activated suggesting that the whole blood cascade system is engaged and that particularly the complement system and to some degree the coagulation system, seems to be a prognostic factor that can be used immediately in the clinic. If we together with our colleagues in Milan and Philadelphia also can show that complement inhibition with AMY-101 is beneficial for the patients, a new treatment for COVID-19 patients can be developed.

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Uppsala University

Uppsala University

Uppsala University

Uppsala University

Uppsala University

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Hjärt-Lungfonden

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