Abstract
COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (β2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X and von Willebrand factor (vWF). Different combinations of autoantibodies associate with different coagulopathies. Previous research revealed similarities between proteins with blood clotting functions and SARS-CoV-2 proteins, adenovirus, and bacterial proteins associated with moderate-to-severe COVID-19 infections. This study investigated whether polyclonal antibodies (mainly goat and rabbit) against these viruses and bacteria recognize human blood-related proteins. Antibodies against SARS-CoV-2 and adenovirus recognized vWF, PDE and PF4 and SARS-CoV-2 antibodies also recognized additional antigens. Most bacterial antibodies tested ( group A streptococci [ GAS ], staphylococci , Escherichia coli [ E. coli ], Klebsiella pneumoniae , Clostridia , and Mycobacterium tuberculosis ) cross-reacted with CL and PF4. while GAS antibodies also bound to F2, Factor VIII, Factor IX, and vWF, and E. coli antibodies to PDE. All cross-reactive interactions involved antibody-antigen binding constants smaller than 100 nM. Since most COVID-19 coagulopathy patients display autoantibodies against vWF, PDE and PF4 along with CL, combinations of viral and bacterial infections appear to be necessary to initiate their autoimmune coagulopathies.
Keywords: E. coli; SARS-CoV-2; adenovirus; antigenic complementarity; autoimmune; autoimmunity; bystander infection; cardiolipin; cross-reactive; mRNA vaccine; platelet factor 4; staphylococcus; streptococcus; thrombocytopenia; thrombosis; vaccine-induced thrombotic thrombocytopenia; von Willebrand Factor.
【저자키워드】 SARS-CoV-2, Autoimmunity, thrombosis, mRNA vaccine, von Willebrand factor., Adenovirus, Autoimmune, thrombocytopenia, platelet factor 4, Staphylococcus, cross-reactive, E. coli, Streptococcus, vaccine-induced thrombotic thrombocytopenia, cardiolipin, bystander infection, antigenic complementarity, 【초록키워드】 COVID-19, antibody, stroke, Proteins, Coagulopathy, Protein, infections, SARS-CoV-2 antibody, mRNA, Research, Patient, von Willebrand factor, Platelet, Bacterial infection, antigens, Bacteria, glycoprotein, serum albumin, Coagulopathies, Mycobacterium tuberculosis, function, Blood, Bacterial, factor VIII, Combination, Interaction, SARS-CoV-2 proteins, similarity, Escherichia coli, PF4, autoantibody, Klebsiella pneumoniae, polyclonal antibody, factor IX, coagulation factor, bystander, Factor, moderate-to-severe COVID-19, antigenic, thrombotic, Clostridia, MOST, tested, develop, virus, involved, investigated, recognize, binding constant, 【제목키워드】 COVID-19, Human, induced,