Can Unconventional Immunomodulatory Agents Help Alleviate COVID-19 Symptoms and Severity?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.

Biochemical screening for SARS-CoV-2 main protease inhibitors

“…Both thimerosal and phenylmercuric acetate and other Hg-containing molecules are thought to have antibacterial properties by their capacity to bind thiol groups in proteins [ 23 ], like the catalytic cysteine of M pro . With regards to other viral infections, very low doses of thimerosal have been additionally found to modulate and promote the host's immune response, promoting Th2-cell responses and inhibiting proinflammatory cytokines and chemokines [ 24 ], which could provide further benefits in the treatment of COVID-19.…”

Cannabis for COVID-19: Can Cannabinoids Quell the Cytokine Storm?

“…The neurological manifestations of COVID-19 and AIDS share some molecular pathways [ 24 ]. Phytocannabinoids, such as Δ 9 -THC and cannabidiol have been demonstrated to reduce inflammatory cytokine storms [ 7–9 , 12–14 , 22 , 25 ]. What’s more, the approval by the US FDA for medical use of cannabidiol and Δ 9 -THC [ 10 ] supports the hypothesis that cannabinoids could reduce the damage caused by COVID-19 by dousing the inflammatory cytokine storm provoked by SARS-CoV-2.…”

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

“…CBD also has anti-inflammatory properties due to the inhibition of cytokine production: IL-1α and β, IL-2, IL-6, interferon-gamma, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and TNF-α [ 149 , 150 , 151 ]. Cannabis constituents THC and CBD also inhibit T-helper type 1 (Th1) cytokines and/or promote an in vitro and in vivo Th2 immune response [ 152 ]. Th1 and the inflammatory immune response profile predominate in COVID-19.…”