Dysregulation of proinflammatory cytokines promotes immune-mediated injuries. Epithelial-cell proliferation and an increase in lung macrophages have both been associated with the 2003 SARS-CoV infection. Proinflammatory cytokines as well as lipopolysaccharide and pathogen-associated molecular patterns (PAMPs) promote macrophage transition which promotes ongoing inflammation. PAMPs are primarily sensed by Toll-like receptors and/or by angiotensin-converting enzyme 2; this interaction serves to activate NF-κB to promotes synthesis and secretion of proinflammatory cytokines. Activated immune cells secrete large amounts of specific proinflammatory cytokines including IL-1, IL-6, IL-8, TNF-α, and TGF-β1 which can promote severe lung injury. As such, immunomodulatory drugs alone may have an impact on the cytokine storm even without the addition of antiviral agents. The central transcription factor, NF-κB, induces angiogenesis during cancer progression; combinations of pharmacological agents, including thalidomide and celecoxib, show promising results in cancer treatment studies. This may be due to a low-level, chronic cytokine storm similar to that described for acute and chronic hepatitis as well as for cirrhosis and hepatoma. As previously described, I have used thalidomide, celecoxib, and low dose cytotoxic agents since 2000 for the successful treatment of a variety of cancers. This regimen is cited or introduced in leading medical journals. Thalidomide is an immunomodulatory agent that modulates the activities of NF-κB in combination with the cyclooxygenase-2 inhibitor, celecoxib. The combination of thalidomide and celecoxib might limit the inflammatory symptoms when used to treat severe COVID-19 pneumonia due to infection with SARS-CoV-2.