TY - JOUR T1 - SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects JF - bioRxiv DO - 10.1101/2022.11.24.517882 SP - 2022.11.24.517882 AU - Celine Boschi AU - David E. Scheim AU - Audrey Bancod AU - Muriel Millitello AU - Marion Le Bideau AU - Philippe Colson AU - Jacques Fantini AU - Bernard La Scola Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/11/28/2022.11.24.517882.abstract N2 - Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than for the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterwards. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines which use spike protein as the generated antigen.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsACE2angiotensin converting enzyme 2CD147cluster of differentiation 147 protein, encoded by the BSG geneCOVID-19coronavirus disease 2019GPAglycophorin ANTDN-terminal domainRBCred blood cellRBDreceptor binding domainRCTrandomized clinical trialSAsialic acidSARS-CoV-2severe acute respiratory syndrome coronavirus 2 ER -