Hence, we hypothesize that vitamin D supplementation will help COVID-19 patients maintain sufficient serum levels of vitamin D as guideline recommended [91, 103], allowing inflammation-upregulated CYP27B1 in respiratory epithelia and immune cells to generate a local high dose of 1,25(OH)2D3 to inhibit CRS and disease progression. The gene discussed is CYP27B1; the disease is COVID-19.