While the contact between SARS-CoV-2 and host results in formation of a trans-species O-glycan bridge and infection is initiated by Tn-antigen production, the pre-existing natural anti-Tn-reactive IgM becomes the first line of defense. The anti-Tn-reactive immunoglobulin M (IgM) is hypothetical identical to the nonimmune anti-A-reactive blood group isoagglutinin activity (Arend, 2017; Arend, 2022), expressed by the ancient poly- and autoreactive germline-encoded immunoglobulin M (IgM) in

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... which is serologically identical to anti-A from the C57BL/10 mouse (Arend and & Nissen, 1977), and hardly arises in response to A-allelic genetic activities. This antibody, which does not occur, or occurs in reduced form in sera from blood group A individuals, may reflect the functions of metazoan defense proteins or lectins, which are considered non-self/self-recognition molecules (VASTA et al., 1994) that monitor expression of the cross-species evolutionary serological Tn antigen (O-GalNAcα1-Ser/Thr-R). Tn (T nouvelle) is an intermediate structure, almost exclusively expressed in tumor tissues and represents a key point of non-self-/self-recognition in metazoan species, while its complementary protein in human plasma, the anti-Tn-reactive IgM, mediates growth process monitoring. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human body via a trans-species Tn formation (Arend, 2020): the viral serine molecule, mobilized from the viral spike (S) protein by the host transmembrane protease serine subtype 2 (TMPRSS2) enzyme, was identified as a fusion molecule (Bertram et al., 2013), essential for SARS-CoV-2 infection, wherein the syngeneic serine might be replaced by the pathogen molecule and the key point of nonself/self-recognition become the target of infection and source of aggressive autoimmunization. While it was argued that anti-Tn is protective against SARS-CoV-2 (Breiman et al., 2021), the hypothetical, cross-species enzyme-substrate comp [...]