Doxycycline Ultra Early Treatment Trial (DUETT): A Randomized Controlled Trial Protocol for the Treatment of COVID-19 -

The study aim is to compare doxycycline (a tetracycline) versus placebo for the treatment of patients with suspected COVID19 caused by SARS-CoV-2 (a positive single-strand RNA virus) in an ultra-early timeframe starting at the time of presentation of a patient at primary health care centres prior to a confirmed PCR result and ending at day seven or two serial negative PCR results are found whichever is earlier. The aim is to abort viral replication, reduce morbidity and mortality, and reduce the R0 of infection transmission. The following arguments support a biologically plausible use of tetracycline for the treatment of COVID19: (1) Metalloproteases (MMPs) are upregulated in human lung tissue in inflammatory lung disease (Greenlee et al. 2007), murine studies show increased expression of MMPs due to coronavirus infection (Zhou et al. 2005). Tetracyclines are known to chelate zinc from MMPs and inhibit MMP function (NYAS Publications ). (2) Tetracyclines inhibit the replication of positive single-strand RNA viruses such as the West Nile virus replication (Michaelis et al. 2007) and Dengue virus replication in tissue culture (Yang et al. 2007). (3) Doxycycline decreases the inflammatory cytokines such as IL-6, IL-1β, and TNF within 3 days reaching a peak effect at 7 days(Castro et al. 2011). A doxycycline is therefore a treatment option that may be able to inhibit SARS-CoV-2 replication, morbidity and mortality and transmission.