Abstract
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.
Highlights
We are in the midst of a pandemic caused by the novel coronavirus SARS-CoV-2. [1] A recent Morbidity and Mortality Weekly Report (MMWR) revealed that among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. [2] Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years
The most common cause of mortality due SARS-CoV-2 is Acute Respiratory Distress Syndrome (ARDS). [1, 2, 7, 8] The objective of this review is to explore the possible role of tetracyclines on decreasing the mortality observed with SARS-CoV-2 as an immunomodulator targeting the COVID-19-associated-Cytokine Storm Syndrome (CSS)/ARDS
There are only two drugs approved under Emergency Use Authorization (EUA) to treat COVID-19 patients with severe disease as discussed above
Summary
We are in the midst of a pandemic caused by the novel coronavirus SARS-CoV-2 (named by WHO on Feb 11, 2020). [1] A recent Morbidity and Mortality Weekly Report (MMWR) revealed that among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. [2] Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years. [1, 2, 7, 8] The objective of this review is to explore the possible role of tetracyclines on decreasing the mortality observed with SARS-CoV-2 as an immunomodulator targeting the COVID-19-associated-CSS/ARDS. The consequences of the overwhelming immune response are: 1) Epithelial and endothelial apoptosis with vascular leakage; 2) Decreased SARS-CoV-1/2 specific T cell immune responses due to the exuberant immune response with T cell apoptosis (and high titer viral replication); and 3) Persistent activation of macrophages, neutrophils, and fibroblasts (with lung fibrosis). [26] Decreasing chemotaxis, secretion of pro-inflammatory cytokines, vascular leakage, and local oxidative stress could be extremely important to prevent COVID-19-associated-ARDS/CSS. Fibrosis is the culmination of many types of chronic inflammatory processes and it can be either beneficial or
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