withdrawal due to the evolution of the epidemic, the arrival of vaccination and because the associated centres could no longer commit to the number of inclusions requested

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.

Inclusion Criteria:

• Man or woman > 45 years old.

• Patient with a positive SARS-CoV-2 PCR

• Patient with ENT and / or respiratory symptoms, without hospitalization criteria (no dyspnea, respiratory rate <22 / min, SaO2 ≥ 94% in ambient air), or digestive signs.

• Patient with at least one of the following risk factors for unfavorable outcome:

  • 70 years, BMI> 30, cardiovascular history (stroke, coronary artery disease, complicated hypertension, cardiac surgery, NYHA III or IV heart failure), respiratory pathology likely to decompensate during viral infection respiratory failure, unbalanced and / or complicated diabètes, respiratory pathology likely to decompensate in the event of of viral infection, patients with renal insufficiency chronic dialysis, .cancer patients under treatment.

Exclusion Criteria:

• Lactose-intolerant patients
• Patient needing immediate hospitalization for any medical reason
• Patient having more than 5 days of clinical symptoms at the inclusion visit
• Patients with a history of allergy to tetracyclines
• Pregnant or lactating women
• Patients participating in another clinical trial
• Patients with photosensitive skin pathology
• Patients treated with anticoagulant
• Patients treated with oral retinoids: isotretinoin, alitretinoin, acitretin
• Patients treated with vitamin A Patients treated with systemic antibiotics for the duration of treatment
• Patients treated with barbiturates, carbamazepine or phenytoin
• Patients with treatment that may have an effect on COVID-19 infection: chloroquine, hydroxychloroquine, remdesivir, ganciclovir, acyclovir, ribavirin, lopinavir-ritonavir
• Patients under guardianship or trusteeship or in safeguard of justice

Double blind