Impact of Doxycycline on COVID-19 Patients with Risk Factors: DYNAMIC, a Multi-Centre, Randomised, Placebo-Controlled, Double-Blind Trial

Abstract Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from matrix metalloproteinases. It is possible their chelating activity may help inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) Tetracyclines are also modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. Moreover, the lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among the tetracyclines, doxycycline has three advantages: its long safety history (side effects are uncommon with no notable risks), its short treatment duration and its low cost.Methods: The trial will involve 330 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as outpatients for early treatment of illness. For logistical reasons and in order to be able to standardise the study as much as possible, recruitment will take place in 6 hospital departments covering the whole of France. For 14 days they will be given either 200mg of doxycycline a day or placebo. Our hypothesis is a considerable reduction in the number of patients hospitalised due to COVID-19 thanks to the treatment of doxycycline.Discussion: This study could have an impact on the overcrowding of patients with COVID-19 at the hospital which is one of the major world-wide problems of this pandemic. This treatment would therefore contribute to supporting the deconfinement strategy by blocking the viral infection early and reducing the infectious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.