We assume the following messages from the human placenta: (1) SARS-CoV-2 entry may be physically blocked with all barrier defense mechanisms; (2) SARS-CoV-2 may be actively combated by three molecular pathways (the type III IFN signaling, secreted miRNAs triggering autophagy and the NF-κB pathway); and (3) if infected, immunomodulation could be employed, which may mitigate violent immune response, possibly soften cytokine storm tightly associated with progression of COVID-19, potentially minimizing damages in cells and tissues, and probably reducing SARS-CoV-2 transmission (Figure 1). This evidence concerns the gene NFKB1 and COVID-19.