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• The severity of SARS-CoV-2 has resulted in a rush to find antiviral treatment for this disease. • Despite in vitro data on efficacy of (hydroxy)chloroquine and azithromycin on SARS-CoV-2, there is no in vivo data that supports this. • We provide pharmacological, methodological and clinical considerations in response to the paper by Gautret et al. The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust. [ABSTRACT FROM AUTHOR]

• Repositioning of old safe drugs against SARS-CoV-2. • Azithromycin and ambroxol could save lives of thousands. • Understanding the cellular uptake mechanism of SARS-CoV-2 aids in treatment design. • Advantageous targeting with inhaled drug delivery system. Knowing the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind to the angiotensin-converting enzyme 2 (ACE2) receptor and to enter cells via endocytosis paved the way for repositioning of old drugs as potential treatment of COVID-19, the disease caused by SARS-CoV-2 infection. This paper highlights the potential of azithromycin and ambroxol to treat COVID-19. Azithromycin and ambroxol share lysosomotropic characteristics, i.e. they penetrate and accumulate inside the late endosomes and lysosomes and may possibly interfere with multiplication of the virus inside cells. In addition, both of these drugs have anti-inflammatory effects. Ambroxol has a proven antiviral effect and a unique stimulatory action on the secretion of surfactant by alveolar type II cells, the main target of SARS-CoV-2. Surfactant may form a fundamental defence mechanism against the virus. Involvement of nasal epithelial cells in SARS-CoV-2 entry suggested advantageous use of inhaled drug delivery of these two drugs over the use of systemic administration. Inhaled drug delivery could aid in targeting the drug to the exact site of action with little or no side effects. To conclude, administration of these two drugs using a special drug delivery system provides two kinds of drug targeting: (i) tissue targeting through using an inhaled drug delivery system to achieve high drug concentrations at the respiratory epithelial tissue that overexpress the ACE2 receptor for virus binding; and (ii) cellular targeting of the virus in the acidic vesicles (late endosomes and lysosomes), which represent the fate of endocytic viruses. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease. [ABSTRACT FROM AUTHOR]

• The mean incubation period is 2-14 days, and the basic reproduction number is 2.24-3.58. • COVID-19 infection should be diagnosed clinically with typical respiratory syndromes coupled with recent exposure. • Chest computerized tomography (CT) could facilitate early diagnosis. • Public health measures, such as isolation, quarantine, social distancing and community containment, can curb COVID-19. • Clinical trials assessing antivirals, chloroquine, hydroxychloroquine, glucocorticoids, convalescent plasma transfusion against COVID-19. In December 2019, the outbreak of the novel coronavirus disease (COVID-19) in China spread worldwide, becoming an emergency of major international concern. SARS-CoV-2 infection causes clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus. Human-to-human transmission via droplets, contaminated hands or surfaces has been described, with incubation times of 2-14 days. Early diagnosis, quarantine, and supportive treatments are essential to cure patients. This paper reviews the literature on all available information about the epidemiology, diagnosis, isolation and treatments of COVID-19. Treatments, including antiviral agents, chloroquine and hydroxychloroquine, corticosteroids, antibodies, convalescent plasma transfusion and vaccines, are discussed in this article. In addition, registered trials investigating treatment options for COVID-19 infection are listed. [ABSTRACT FROM AUTHOR]