A cursory examination of the recent coronavirus literature was revelatory in that SARS-CoV and MERS-CoV have been the subject of very many experiments utilizing a vast array of immortalized human cells. It would appear to be standard practice in surveillance studies to challenge human cell cultures over-expressing known entry targets such as human angiotensin-converting enzyme 2 (ACE2) in the case of SARS-CoV and dipeptidyl peptidase 4 (DPP4) in the case of MERS-CoV.

In a recent study, the ink of which may not yet have dried, a human antibody targeting the receptor-binding domain (RBD) of the (original) SARS-CoV virus enabled Antibody-Dependent Enhancement (ADE), facilitating viral fusion preferentially with CD32A+ rather than ACE2+ cellular membranes. (Wan, Y., et al. (2020). "Molecular mechanism for antibody-dependent enhancement of coronavirus entry." Journal of virology 94(5).)

This phenomenon has also been observed in other mammals infected with CoV strains, depending on the locale of the antigenic determinant, the virus can circumvent and potentially exhibit an enhanced rate of infection due to antibody-binding of one RBD on one subunit of the spike protein homo-trimer; initiating an an alternative route of infection. ADE has been observed in other viruses, notably HIV and Ebola strains, although the mechanisms of the aforementioned and hitherto most notorious viruses have had decades of elucidation. Far less time and resources have been devoted to coronaviridae, a seemingly benign pathogen before the the turn of the century up until the emergence of the first respiratory, lethal pneumonia-inducing strains. The downstream effects of human ADE of SARS-CoV2 are completely unknown in humans, and what little mammalian data we do have this mode of infection elicited a significantly more severe syndrome.

Is there a mitigation strategy given the potential existence of a biomolecular mechanism, whereby an unknown subset of potential epitopes have demonstrated an alternative route of infection, preferentially fusing into immuno-associated cell membranes in previously inoculated individuals? The very limited mammalian data suggests that felines, previously inoculated with spike protein antigens, exhibited far more detrimental effects and increased rates of mortality upon subsequent viral exposure, compared to the control group.

(Hohdatsu T, Yamada M, Tominaga R, Makino K, Kida K, Koyama H. 1998. Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus. J Vet Med Sci 60:49 –55. https://doi.org/10.1292/jvms.60.49.)

(Vennema H, de Groot RJ, Harbour DA, Dalderup M, Gruffydd-Jones T, Horzinek MC, Spaan WJ. 1990. Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization. J Virol 64:1407–1409.)