Abstract: Correspondence: H. Yi, South Southern University of Science and Technology, Shenzhen, China (yhg926@gmail.com). Clinical Infectious Diseases®  2020;71(15):884–7 © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciaa219 Is Hydroxychloroquine a Possible Postexposure Prophylaxis Drug to Limit the Transmission to Healthcare Workers Exposed to Coronavirus Disease 2019? To the Editor—We read with great interest the study by Yao et al [1] reporting that hydroxychloroquine has better antiviral activity than chloroquine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is associated with a high lung-to-plasma concentration ratio and immunomodulatory effects. Moreover, the authors highlighted that hydroxychloroquine half maximal effective concentration values “tended to decrease with longer incubation times” and that, in the simulation model, the lung trough concentrations were still above the target concentration on day 10 after a 5-day course of hydroxychloroquine. Besides household contacts, SARSCoV-2 can be acquired in hospital settings, with healthcare workers (HCWs) attending at invasive procedures on the respiratory tract (ie, intubation, endotracheal tube aspiration, or bronchoscopy) at the highest risk. Accidently infected HCWs represent an important source of infection during the period that they are asymptomatic or presymptomatic, as they can transmit the virus to household contacts and to patients seeking medical care for reasons unrelated to SARS-CoV-2 infection. For these reasons, we suggest preventive strategies for those accidentally exposed to SARS-CoV-2 such as preexposure or postexposure prophylaxis to avoid viral transmission, as largely accepted for those exposed to other viral agents such as human immunodeficiency virus (HIV) [2]. Chloroquine and hydroxychloroquine are able to inhibit replication at early stages of viral infection, increasing endosomal pH at the time of virus/cell fusion, as well as impairing the glycosylation of cellular receptors of many viruses including coronavirus [3]. In contrast, no similar effect on early phases of coronavirus infection has been reported for other drugs proposed for SARS-CoV-2 treatment, which are able to interfere only after cell infection, affecting protease cleavage (protease inhibitors) or viral genome replication (remdesivir or ribavirin). These effects of chloroquine on early phases of viral replication permit the attenuation of vertical transmission in an animal model of Zika virus infection, significantly reducing brain viral load, and make cells refractory to SARS-CoV infection in an in vitro model [4, 5]. Hydroxychloroquine, the HIV protease inhibitors (particularly lopinavir), ribavirin, and remdesivir are the most promising drugs proposed for coronavirus disease 2019 (COVID-19) treatment, but currently no drug has been proposed for postexposure or preexposure prophylaxis for those accidently exposed to SARS-CoV-2 [6]. On the basis of these investigations, we believe that hydroxychloroquine can be effective in preventing respiratory tract invasion in HCWs exposed to SARSCoV-2 and that hydroxychloroquine administration as a prophylactic agent could be particularly useful for HCWs attending to high-risk procedures on the respiratory tract in COVID-19 patients. Hydroxychloroquine’s effectiveness..