Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Medical Hypotheses 143 (2020) 110110 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy Letter to Editors Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19 T ABSTRACT Current formulations and dose regimens of hydroxychloroquine (HCQ) put patients at risk of harm. An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Further, almost all of the trials registered do not consider dosage adjustment in the elderly, a patient population most likely to require HCQ treatment. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. As this simple formulation progressed to phase II studies, safety data can be used to immediately enable phase II trials in COVID-19. The COVID-19 (SARS-CoV-2) pandemic has had devastating health consequences worldwide [1], and life has been brought to a standstill as the world awaits a vaccine. Meanwhile, many patients continue to fall critically ill and, in the absence of a vaccine, antivirals and other treatments to alleviate the effects of the disease are urgently sought. In recent months, since the outbreak of COVID-19, a large number of clinical trials have been registered on ClinicalTrials.gov with the aim of repurposing medicines to reduce the severity of the disease [2]. Chloroquine and hydroxychloroquine (HCQ) were two of the earliest drugs to receive attention as possible repurposable treatment options for COVID-19 [3]. Indeed, a number of studies investigated their anti-SARS-CoV activity as early as 2003 [4–6]. However, the potential efficacy of HCQ must be balanced against its side-effects, particularly those associated with QT elongation, which is exacerbated by age, comorbidities and administration with other agents (such as azithromycin) that prolong the QT interval [7]. A recent analysis of NHS (UK) electronic health records revealed that the most striking risk factors for COVID-19 death were age and male gender [8], and those same risk factors have been identified previously in the context of drug induced QT elongation [9,10]. Concerns associated with severe side effects are such that the FDA and EMA now formally recommend against taking HCQ for COVID-19 infection unless it is being prescribed in the hospital or as part of a clinical trial [11,12]. Our analysis of the 185 trials registered with ClinicalTrials.gov (13th May 2020) using the search terms “COVID-19 and..