Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
Associated Clinical Trials
Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture.
Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement.
A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways
Smallpox inhibitor of complement enzymes (SPICE): regulation of complement activation on cells and mechanism of its cellular attachment
Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodies
Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63
Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation
Treatment with anti-C5a antibody improves the outcome of H7N9 virus infection in African green monkeys
Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development.
Interaction between Multimeric von Willebrand Factor and Complement: A Fresh Look to the Pathophysiology of Microvascular Thrombosis
C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe Hypertension
Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance
Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G
Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.
Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis
Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports
Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.
Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition.
Anti-heart antibodies levels and their correlation with clinical symptoms and outcomes in patients with confirmed or suspected diagnosis COVID-19.
Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs.
Transcriptional Differences for COVID-19 Disease Map Genes between Males and Females Indicate a Different Basal Immunophenotype Relevant to the Disease
A meta-meta-analysis: Evaluation of meta-analyses published in the effectiveness of cardiovascular comorbidities on the severity of COVID-19.
Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics.
Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets.
The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System.
Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs.
Pharmacokinetic and Pharmacodynamic Evaluation of Ravulizumab in Adults with Severe Coronavirus Disease 2019.
SARS-CoV-2 associated Complement genetic variants possibly deregulate the activation of the Alternative pathway affecting the severity of infection.
The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19.
Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment.
Investigating Cellular Trajectories in the Severity of COVID-19 and Their Transcriptional Programs Using Machine Learning Approaches.
Thrombotic microangiopathy (aHUS/iTTP) reported so far in Covid-19 patients: The virus alone or an omnium gatherum of mechanisms and etiologies?
Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses.
COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on "Two-Path Unifying Theory" of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy.
A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19.
COVID-19 myocarditis: quantitative analysis of the inflammatory infiltrate and a proposed mechanism.
Blood Clotting Disorders
Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.