PB0059 - Influence of complement system genomic variations on the course of COVID-19

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

JG

Jaromír Gumulec

Deputy Head Physician for Health Care
Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava
Ostrava, Moravskoslezsky kraj, Czech Republic

Co-Author(s)

JM

Jan Máca

Deputy Head of Education and Science
Department of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava, Czech Republic, Department of Intensive Care and Forensic Studies, Faculty Of Medicine, University of Ostrava, Czech Republic, Institute of Physiology and Pathophysiology, Faculty Of Medicine, University of Ostrava, Czech Republic
Ostrava, Moravskoslezsky kraj, Czech Republic
JS

Jiří Sagan

Physician
Department of Infectious Medicine, University Hospital Ostrava, and Faculty of Medicine, University of Ostrava, Czech Republic
Ostrava, Moravskoslezsky kraj, Czech Republic
J�

Jozef Škarda

Head of Department
Institute of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Czech Republic
Ostrava, Moravskoslezsky kraj, Czech Republic
MK

Martin Kutěj

Physician
Department of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava, Czech Republic, Department of Intensive Care and Forensic Studies, Faculty Of Medicine, University of Ostrava, Czech Republic, Department of Intensive Care and Forensic Studies, Faculty Of Medicine, University of Ostrava, Czech Republic, Faculty Of Medicine, Masaryk University in Brno, Czech Republic
Ostrava, Moravskoslezsky kraj, Czech Republic
NC

Nela Chobolova

Deputy Head of Department
Department of Clinical Biochemistry, Institute of Laboratory Medicine, University Hospital Ostrava, University of Ostrava, Czech Republic
Ostrava, Moravskoslezsky kraj, Czech Republic
DK

David Kaspřák

Laboratory assistant
Laboratory of Molecular Biology, Spadia LAB JSC, Czech Republic
Nový Jičín, Moravskoslezsky kraj, Czech Republic

Background: The pandemic of SARS-CoV-2 is a severe worldwide problem increasing morbidity and mortality.1, 2 Severe COVID-19 presents as multiple organ failure caused by systemic inflammation, thrombin generation, and hypofibrinolysis. Diffuse microvascular thrombi and inter-alveolar deposits of complement fragments are observed. The enhanced immunothrombosis is mediated by direct overactivation of complement by virus surface components or damaged cells.3-5

Aims: The study aimed to find whether genetic changes responsible for complement dysregulation known in atypical hemolytic-uremic syndrome (aHUS) can be found in severe COVID-19 patients.

Methods: The study included adult COVID-19 subjects undergoing extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome. Two independent physicians signed informed consent, and the study was approved by a local ethics committee (No. 109/2021) and supported by the University Hospital fund. Next-Generation Sequencing Panel of C3 component, membrane cofactor protein (CD46), complement factor B (CFB), complement factor H (CFH), complement factor H related genes 1-5 (CFHR 1-5), diacylglycerol Kinase Epsilon, thrombomodulin (THBD) and mannose-binding lectin (MBL) genes were performed, with confirmations of positive results by Sanger sequencing.

Results: Twenty-two patients (13 were male) aged 33 to 65 years were included. No pathogenic gene variants in the C3, CD46, CFB, CFH genes, CFHR 5, CFI, THBD were detected. However, we have shown the presence of modifiers (CFH-H3 haplotype, MCP-GGAAC haplotype, and CFH/CFHR1), which may, together with triggers (infection), increase the severity of the disease (aHUS).6-8 Moreover, we have identified single nucleotide polymorphisms in exon 1 at codon 52 (c.154C>T) and 54 (c.161G>A) of the MBL2 gene promoter associated with low serum levels or dysfunctional MBL and higher incidence of infections.

Conclusion(s): We did not detect any complement-related pathogenic gene variants known in aHUS. Thus, It is unlikely that complement dysregulation is the main factor influencing immunothrombosis in a cohort of the most severe COVID-19 patients.