The University of Louisville Journal of Respiratory Infections


The author(s) received no specific funding for this work.


We are in the midst of a pandemic due to the novel coronavirus SARS-CoV-2. Innovative therapies are in the lookup around the world. Recently, chloroquine and hydroxychloroquine in addition to azithromycin were proposed to be used in patients with severe disease even though strong evidence is lacking. We propose the use of tetracyclines in addition to anti-virals early in the curse of the disease in order to prevent the cytokine storm syndrome associated with COVID-19 and prevent ARDS. The proposed mechanisms of tetracyclines are: 1) anti-apoptotic properties; 2) decrease the Myeloperoxidase and ROS releaser from immune cells; 3) decrease neutrophil and monocyte migration and chemotaxis; 4) decrease the secretion of pro-inflammatory and vasoactive cytokines from macrophages (IL-1 beta, IL-8, and TNF-alpha); 5) inhibition of iNOS expression; 6) inhibition of chemotaxis of peripheral monocytes; 7) inhibition of IL-6 production and its receptor system; 8) prevention of fibrosis; and 9) inhibition of metalloproteinases (particularly MMP-2 and 9). Tetracyclines are well-known drugs with lower costs, and are not associated with adverse effects like QT prolongation. Clinical trials are needed to test our hypothesis.



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