To further understand the interplay between SARS-CoV-2 and pIgR, we have investigated which viral proteins may cause the downregulation of pIgR and discovered that ORF8 is capable of potently diminishing the expression of pIgR, thus potentially dampening the mucosal immunity by blocking the secretion of dIgA and pIgM; as a result, it promotes SARS-CoV-2’s infection of the respiratory epithelial cells. The gene discussed is PIGR; the disease is infection.