The personnel responsible for caring of patients infected by the SARS-CoV-2 virus: doctors, nurses and paramedics working at Intensive Care Units (ICUs)), are at high risk of SARS-CoV-2 infection. Epidemiological figures suggest a high morbidity and mortality of doctors responsible for the care of infected individuals, a factor that darkens further the panorama of the current pandemic. The present proposal has two specific aims: (i) to evaluate whether hydroxychloroquine, used prophylactically at low dose (400mg/week for three months), protect against SARS-CoV-2 infection; and (ii) to examine whether exhaustion and senescence of immune system cells are associated to higher risk of SARS-CoV-2 infection. This is a PILOT STUDY, a Phase III double-blind, randomized, placebo-controlled clinical study in which we assess the clinical effect of the prophylactic administration of hydroxychloroquine vs. placebo to healthcare workers working at our University Hospital (HUN). Participants in each arm (n = 43) will be administered with a unique loading dose of 800 mg of hydroxychloroquine the first day followed by 400 mg/week for 90 days. The population to be studied (uninfected healthcare personnel) will be highly exposed to SARS-CoV-2 infection. Taking into account that around 80% do not express symptoms or that these are mild, an active search should be made for individuals who become infected while participating in the study. For this, once the informed consent form is signed, the molecular test for the diagnosis of SARS-CoV-2 infection by RT-PCR will be carried out every 4 days in order to determine as closely as possible the moment the participant become positive. The results of the diagnostic RT-PCR tests will be confronted with: (i) the results of immune monitoring of at least 30 immunological parameters in leukocytes (number and phenotype of: PMN cells, monocytes, T- and B-lymphocytes and NK-cells) and in plasma (levels of IL-2, IL-6, IL-7, IL-10, GM-CSF, TNF-a, IP-10, MCP-1, MIP-IA, IL-1, CRP, Type IFN-alpha and IFN-betta), analyzed by automated flow cytometry software such as tSNE, SPADE, FlowSOM, among others (see attached file); and (ii) the daily recording of data on the presence or absence of signs and symptoms associated with SARS-Cov-2 infection. For the recording of immune monitoring 20mL blood samples will be taken at eight-time points (day 0) and at 8, 15, 21, 30, 45, 60 and 90 days in order to monitor the baseline of immune functionality throughout the 90 days of the study. In summary, this proposal seeks to identify immunological markers of the immune system important for defense against SARS-CoV-2, that may be useful as prognostic markers for clinical response and treatment of patients with COVID-19, and also, to evaluates whether Hydroxychloroquine, used prophylactically, has a role in protecting against SARS-CoV-2 infection in a group of healthcare workers. If hydroxychloroquine, as we all hope, turns out to be an agent that prevent SARS-Cov-2 infection, a significant group of healthcare workers at HUN at risk of becoming ill during the epidemiological peak (expected May 1st), will be protected thanks to their participation in this study.