key: cord-0910681-8ooirpzf
authors: Gironi, Laura Cristina; Damiani, Giovanni; Zavattaro, Elisa; Pacifico, Alessia; Santus, Pierachille; Pigatto, Paolo Daniele Maria; Cremona, Ottavio; Savoia, Paola
title: Tetracyclines in COVID‐19 patients quarantined at home: Literature evidence supporting real‐world data from a multicenter observational study targeting inflammatory and infectious dermatoses
date: 2020-12-29
journal: Dermatol Ther
DOI: 10.1111/dth.14694
sha: 8657bb553eb829060df830456540a866dc89725c
doc_id: 910681
cord_uid: 8ooirpzf

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID‐19 outbreak, several dermatological patients contracted SARS‐CoV‐2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID‐19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21‐67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID‐19 outpatients with mild symptoms.

The rapid pandemic spread overwhelmed healthcare systems capacity worldwide, forcing physicians to quarantine at home both confirmed and suspected COVID-19 patients with mild respiratory symptoms. 1 At the same time, no treatment protocols were approved for these patients, consequently only a symptomatologic therapy was delivered.

Furthermore, several antivirals and immunomodulators which seem to have shown anti-COVID-19 effects (ie, lopinavir/ritonavir, tofacitinib etcetera) are currently recommended by the World Health Organization (OMS) only in the context of clinical trials. 2 Thus, drug reproposal and drug discovery are magnetizing both physician and scientists' efforts for their potential; in silico evaluation and pharmacoepidemiology play a pivotal role in scanning the possible candidate against COVID-19. 3, 4 In this scenario dermatology offers a wide armamentarium of immunomodulatory and immunosuppressant drugs that may contrast or even prevent the cytokines storm due to COVID-19 hyperinflammatory phase. [5] [6] [7] [8] Remarkably, tetracyclines (TetraC) were candidate as promising drugs to fight against COVID-19 pandemics due to their potential antiviral effect. 9 TetraC represent a wide spectrum polyketide antibiotic that show a bacteriostatic effect on bacteria, that act through inhibition of translation and, consequently, the bacterial growth. The first members of the TetraC group to be discovered were chlortetracycline and oxytetracycline in the 1940s.

In the following years, the TetraC family has expanded a lot; currently, it includes more than a dozen molecules. In the dermatological field, TetraC have been widely used for several decades to treat both Laura Cristina Gironi and Giovanni Damiani contributed equally to this study. infectious and noninfectious diseases ( Table 1) . As a matter of fact, TetraC are largely used in dermatology also for their additional properties, such as antioxidative, immunomodulatory, antiapoptotic, proproliferation, and proangiogenetic ones, to treat several inflammatory and immunemediated skin disorders summarized in Table S1 . Among TetraC in daily practice, Doxycycline (DOX) and Minocycline (MIN) are the most prescribed ones due to their safety profile, availability and efficacy, adequate to treat in an outpatient setting. 10 Their profiles together with their antiviral property make TetraC an encouraging candidate to treat dermatological outpatients with mild forms of COVID-19 (Table S2) . Furthermore, during the Italian lockdown (March-May 2020) no pharmacological treatment, unless symptomatic ones, were approved for mild COVID-19 and patients had to stay in their home and use telemedicine. Thus, we performed an observational study on dermatological outpatients with mild COVID-19 and concurrent dermatoses with TetraC indication.

TetraC displayed in humans and animals interesting antiviral properties not previously tested on Coronaviruses. Furthermore, no therapeutic protocols were present for mild COVID-19 outpatients, so dermatological patients treated with TetraC at home and positive for SARS CoV-2 represent a unique real-life opportunity to evaluate in vivo TetraC antiviral properties.

The present study fulfilled the ethical principles regarding human experiments contained in the Declaration of Helsinki and their subsequent, included the last one in October 2013. The study received a full approval by ethical committees of all the involved institutions and every patient signed an informed consent form.

We performed a multicenter, prospective observational study. the most severe symptom. Patients were also asked to register daily temperatures and other signs and symptoms.

In this subset, we selected the patients who matched all the following (Table S2) . These findings are promising also for severe COVID-19 patients in which IL-6 is the main driver of the "cytokinic storm" and consequent mortality, as testified by the encouraging results obtained using tocilizumab, an IL-6 receptor inhibitor, on lung lesions. 33 

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