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.

Autoimmune cardiopathies (AC) following COVID-19 and vaccination against SARS-CoV-2 occur at significant rates but are of unknown etiology. This study investigated the possible roles of viral and bacterial mimicry, as well as viral-bacterial co-infections, as possible inducers of COVID-19 AC using proteomic methods and enzyme-linked immunoadsorption assays. BLAST and LALIGN results of this study demonstrate that SARS-CoV-2 shares a significantly greater number of high quality similarities to some cardiac protein compared with other viruses; that bacteria such as Streptococci, Staphylococci and Enterococci also display very significant similarities to cardiac proteins but to a different set than SARS-CoV-2; that the importance of these similarities is largely validated by ELISA experiments demonstrating that polyclonal antibodies against SARS-CoV-2 and COVID-19-associated bacteria recognize cardiac proteins with high affinity; that to account for the range of cardiac proteins targeted by autoantibodies in COVID-19-associated autoimmune myocarditis, both viral and bacterial triggers are probably required; that the targets of the viral and bacterial antibodies are often molecularly complementary antigens such as actin and myosin, laminin and collagen, or creatine kinase and pyruvate kinase, that are known to bind to each other; and that the corresponding viral and bacterial antibodies recognizing these complementary antigens also bind to each other with high affinity as if they have an idiotype-anti-idiotype relationship. These results suggest that AC results from SARS-CoV-2 infections or vaccination complicated by bacterial infections. Vaccination against some of these bacterial infections, such as Streptococci and Haemophilus, may therefore decrease AC risk, as may the appropriate and timely use of antibiotics among COVID-19 patients and careful screening of vaccinees for signs of infection such as fever, diarrhea, infected wounds, gum disease, etc.