The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the
patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of
reducing or even abolishing the cytokine explosion and thus the evolution towards a serious
form of the disease which can lead to death.
Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is
known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival.
Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit
COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may
also be able to inhibit the replication of positive-polarity single-stranded RNA viruses,
such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are
modulators of innate immunity (anti-inflammatory activity), a property used in the treatment
of inflammatory skin diseases for many years. These modulating effects are noted on several
targets of innate immunity: They can decrease the expression of NFKB, the release of
inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and
free radical release.
Tetracyclines could therefore participate in limiting the cytokine release induced by
COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to
inhibit viral replication.