The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses its spike protein to enter the host cells. Vaccines that introduce the spike protein into our body to elicit virus-neutralizing antibodies are currently being developed. In this article, we note that human host cells sensitively respond to the spike protein to elicit cell signaling. Thus, it is important to be aware that the spike protein produced by the new COVID-19 vaccines may also affect the host cells. We should monitor the long-term consequences of these vaccines carefully, especially when they are administered to otherwise healthy individuals. Further investigations on the effects of the SARS-CoV-2 spike protein on human cells and appropriate experimental animal models are warranted.