Our goal was to evaluate CD44, OPN, and COX-2 expression in three groups of pregnant women (healthy and unvaccinated, COVID-positive and unvaccinated, and COVID-vaccinated and COVID-negative) to assess possible physiopathological pathways for the alterations in placental architecture consecutive to inflammatory responses, which may be influenced by viral infections or vaccine-induced immune modulation. Here, SPP1 is linked to viral infectious disease.