Reaching beyond the possibilities of currently evaluated drugs for single targets of the cytokine cascade, the inhibition of NF-κB pathway—preferably in parallel at several sensitive points (Figure 1)—could provide the unique potential to inhibit the release of multiple cytokines simultaneously, in particular strongly pro-inflammatory cytokines including IL-1, IL-6, TNFα, and chemokines including MIP-1α, MIP-1β, MCP-1, as well as adhesion molecules that are increased during highly inflammatory processes during acute COVID-19 stages. Here, NFKB1 is linked to COVID-19.