key: cord-0686505-c51lfwd6 authors: Kavanagh, Oisín; Marie Healy, Anne; Dayton, Francis; Robinson, Shane; O'Reilly, Niall J.; Mahoney, Brian; Arthur, Aisling; Walker, Gavin; Farragher, John P. title: Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 date: 2020-07-15 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110110 sha: 243d15fcd77669e1a17a5ef21a89bd9bcf661141 doc_id: 686505 cord_uid: c51lfwd6 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. 2 25 The COVID-19 (SARS-CoV-2) pandemic has had devastating health consequences 26 worldwide 1 , and life has been brought to a standstill as the world awaits a vaccine. Meanwhile, 27 many patients continue to fall critically ill and, in the absence of a vaccine, antivirals and other 28 treatments to alleviate the effects of the disease are urgently sought. 29 30 In recent months, since the outbreak of COVID-19, a large number of clinical trials have been 31 registered on ClinicalTrials.gov with the aim of repurposing medicines to reduce the severity 32 of the disease 2 . Chloroquine and hydroxychloroquine (HCQ) were two of the earliest drugs to 33 receive attention as possible repurposable treatment options for COVID-19 3 . Indeed, a number 34 of studies investigated their anti-SARS-CoV activity as early as 2003 4-6 . However, the 35 potential efficacy of HCQ must be balanced against its side-effects, particularly those 36 associated with QT elongation, which is exacerbated by age, comorbidities and administration 37 with other agents (such as azithromycin) that prolong the QT interval 7 . A recent analysis of 38 NHS (UK) electronic health records revealed that the most striking risk factors for COVID-19 39 death were age and male gender 8 , and those same risk factors have been identified previously 40 in the context of drug induced QT elongation 9,10 . Concerns associated with severe side effects 41 are such that the FDA and EMA now formally recommend against taking HCQ for COVID- Effects of chloroquine on 178 viral infections: An old drug against today's diseases? New insights into the 181 antiviral effects of chloroquine Hydroxychloroquine in SLE: Old drug, new perspectives. 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