Abstract: Letters ­ Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-­ CoV-2 infection and severe COVID-19 The use of hydroxychloroquine (HCQ) in the prophylaxis and treatment of coronavirus disease 2019 (COVID-19) has received significant attention by politicians and media figures. This has occurred despite limited data supporting its efficacy in COVID-19 as well as considerable concern about its safety when used at high doses (>400 mg daily) and in combination with other QT interval prolonging drugs.1–4 An inaccurate narrative has emerged in recent weeks that patients with systemic lupus erythematosus (SLE) who are taking HCQ as a baseline therapy are less affected by or do not develop COVID-19.5–7 This assumption has been challenged by Monti and Montecucco,8 referencing data from the COVID-19 Global Rheumatology Alliance registry on patients with rheumatic disease that previously identified 19/110 (17%) patients with SLE.9 A case series of 17 patients with lupus or antiphospholipid syndrome who developed COVID-19 on a median HCQ dose of 400 mg daily (median HCQ blood level of 648 ng/mL) has since become available. 10 As of 17 April 2020, we have now identified 80 patients with SLE and COVID-19 in the global physician-­reported registry. Patients were predominantly female (72/80, 90%) and less than 65 years of age (69/80, 86%). Importantly, 64% (51/80) of patients with SLE were taking an antimalarial (HCQ or chloroquine) prior to infection with severe acute respiratory syndrome coronavirus 2 (SARS-­ CoV-2) (30% as monotherapy). Notably, 21.1% (121/573) of all reported patients with rheumatic disease in the registry were treated with an antimalarial prior to onset of COVID-19, yet 49.6% (60/121) required hospitalisation. In patients with SLE, frequency of hospitalisation with COVID-19 did not differ between individuals using an antimalarial versus non-­users (55% (16/29) vs 57% (29/51), p=ns; χ2 test). In patients with lupus, escalation to maximum level of care (non-­invasive ventilation, invasive ventilation or extracorporeal membrane oxygenation (ECMO)) was required regardless of HCQ use (online supplementary table S1). Thus, patients with lupus—even if they are using an antimalarial such as HCQ as baseline therapy—can develop SARS-­CoV-2 infection and severe COVID-19 at similar frequency as lupus patients not on antimalarials. 1386 Ann Rheum Dis October 2020 Vol 79 No 10 Ann Rheum Dis: first published as 10.1136/annrheumdis-2020-217690 on 7 May 2020. ­ There are currently >40 ongoing clinical trials examining HCQ in the prophylaxis or treatment of SARS-­CoV-2 infection that employ highly variable strategies with regards to dosing (total oral loading dose 400–1400 mg), duration and time of initiation.11 However, dosing considerations of HCQ in COVID-19 may be critical to understand why patients with lupus may not be protected from SARS-­CoV-2 infection. Similar to in vitro studies indicating activity of antimalarial 4-­aminoquinoline derivatives against SARS-­CoV-1 and MERS-­CoV,12 13 a putative role for HCQ in the treatment of COVID-19 has been suggested by its antiviral effect in cell culture systems.14 15 Given the assumptions made when moving from a cell-­based model to a complex in vivo system, in vitro potency cannot be expected to translate into in vivo efficacy,16 as observed for chloroquine in a..