Therapeutic Strategies with Synbiotics, Thalidomide, and Celecoxib for
Severe COVID-19 Pneumonia
Abstract
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.