Glycan is an essential molecule that controls and drives life in a precise direction. The paucity of research in glycobiology may impede the significance of its role in the pandemic guidelines. The SARS-CoV-2 spike protein is heavily glycosylated, with 22 putative N-glycosylation sites and 17 potential O-glycosylation sites discovered thus far. It is the anchor point to the host cell ACE2 receptor, TMPRSS2, and many other host proteins that can be recognized by their immune system; hence, glycosylation is considered the primary target of vaccine development. Therefore, it is essential to know how this surface glycan plays a role in viral entry, infection, transmission, antigen, antibody responses, and disease progression. Although the vaccines are developed and applied against COVID-19, the proficiency of the immunizations is not accomplished with the current mutant variations. The role of glycosylation in SARS-CoV-2 and its receptor ACE2 with respect to other putative cell glycan receptors and the significance of glycan in host cell immunity in COVID-19 are discussed in this paper. Hence, the molecular signature of the glycan in the coronavirus infection can be incorporated into the mainstream therapeutic process.