Taken together, these findings highlight the critical role of the COX-2/PGE2 pathway in modulating IBV strain-specific effects of IBV on macrophage survival, with DMV/1639 infection primarily inducing necroptosis, which was mitigated by COX-2 inhibition and PGE2 pathway modulators, whereas Conn A5968 infection led to significant cell death via apoptosis and necrosis, further exacerbated by COX-2 and PGE2 receptor inhibitors. This evidence concerns the gene PTGS2 and infection.