Can hydroxychloroquine be useful in the prevention of COVID-19? An Italian survey in dermatologic and rheumatologic patients already under treatment
Authors: Maria Vastarella, Angela Patrì, Maria Carmela Annunziata, Mariateresa Cantelli, Paola Nappa, Marco Tasso, Luisa Costa, Francesco Caso, Gabriella Fabbrocini
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: The World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. To date, there is an urgent need for effective drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chloroquine and hydroxychloroquine (HCQ) have been shown to inhibit SARS-CoV-2 in vitro, and HCQ seems more effective than chloroquine.1Liu J. Cao R. Xu M. et al.Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.Cell Discov. 2020; 6: 16Crossref PubMed Scopus (1501) Google Scholar,2Yao X. Ye F. Zhang M. et al.In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [e-pub ahead of print].https://doi.org/10.1093/cid/ciaa237Date accessed: April 26, 2020Google Scholar The aim of our research was the evaluation of HCQ preventive effects on the acquisition of SARS-CoV-2 infection. We conducted an observational retrospective study through a telephone survey among patients in treatment with HCQ for chronic dermatologic or rheumatologic diseases referring to the Dermatologic and Rheumatologic Clinics of the University of Naples Federico II, Italy. The survey and its results are summarized in Table I, Table II, Table III.Table IQuestions asked in the telephone survey and dermatologic patients' answersPatientAge, yDermatologic diagnosisHCQ dose, mg/dDuration (ongoing?)History of respiratory symptoms or fever∗In the last 2 months.Exposure to people with respiratory symptoms or fever∗In the last 2 months.Exposure to established COVID-19 casesHCQ-related toxicity158LPP20018 mo (yes)NoNoNoNone257LPP+FFA20030 mo (yes)NoNoNoNone317LPP2007 mo (yes)NoNoNoNone460LPP20012 mo (yes)NoNoNoNone559LPP20024 mo (yes)NoNoNoNone658LLP20012 mo (yes)NoNoNoNone731LLP60018 mo (yes)NoNoNoNone864LLP20012 mo (yes)NoNoNoNone965LLP20012 mo (yes)NoNoNoNone1047LLP20015 mo (yes)NoNoNoNone1162LLP2007 mo (yes)NoNoNoVisual decline1266LLP2003 mo (yes)NoNoNoVisual fogging1358LLP20012 mo (yes)NoNoNoNone1474LLP20012 mo (yes)NoNoNoNone1556LLP20012 mo (yes)NoNoNoNone1661LLP+AGA20015 mo (yes)NoNoNoNone1785FFA20012 mo (yes)NoNoNoNone1862LLP2006 mo (yes)NoNoNoNone1948LLP2005 mo (yes)NoYes, a son with feverNoNone2055LLP2005 mo (yes)NoNoNoNone2168LLP20012 mo (yes)NoNoNoNone2260LLP20011 mo (yes)NoNoNoNone2370LLP20014 mo (yes)NoNoNoNone2472LLP20014 mo (yes)NoNoNoNone2529LLP20015 mo (yes)NoNoNoNone2656LLP20012 mo (yes)NoNoNoNone2740LLP20015 mo (yes)Yes, fever ≤37.2°CNoNoNone2838LLP20032 mo (yes)NoNoNoNone2918DLE20010 mo (yes)NoNoNoNone3067LLP and RA20036 mo (yes)NoNoNoNoneAGA, Androgenetic alopecia; DLE, discoid lupus erythematosus; FFA, frontal fibrosing alopecia; HCQ, hydroxychloroquine; LPP, lichen planopilaris; RA, rheumatoid arthritis.∗ In the last 2 months. Open table in a new tab Table IIQuestions asked in the telephone survey and rheumatologic patients' answersPatient, No.Age, yRheumatologic diagnosisHCQ dose, (mg/d)Duration (ongoing?)History of respiratory symptoms or fever∗In the last 2 months.Exposure to people with respiratory symptoms or fever∗In the last 2 months.Exposure to established COVID-19 casesHCQ-related toxicity137SLE200 × 218 mo (yes)NoNoNoNone255SA200 × 224 mo (yes)NoNoNoNone354SA200 × 224 mo (yes)NoNoNoNone459SA200 × 220 mo (yes)NoNoNoNone531UCTD200 × 236 mo (yes)NoNoNoNone661SLE200 × 236 mo (yes)NoNoNoNone731SLE200 × 230 mo (yes)NoNoNoNone843Myositis200 × 28 mo (yes)NoNoNoNone953SLE200 × 236NoNoNoNone1051SLE200 × 28 mo (yes)NoNoNoNone1164Sjögren200 × 2170 mo (yes)NoNoNoNone1259Sjögren200 × 260 mo (yes)NoNoNoNone1334UCTD200 × 24 mo (yes)NoNoNoNone1433UCTD200 × 229 mo (yes)NoNoNoNone1547SLE200 × 212 mo (yes)NoNoNoNone1651UCTD200 × 260 mo (yes)NoNoNoNone1732UCTD200 × 224 mo (yes)NoNoNoNone1867UCTD200 × 216mo (yes)NoNoNoNone1936SLE200 × 219 mo (yes)NoNoNoNone2053SLE200 × 248 mo (yes)NoNoNoNone2152SLE200 × 2240 mo (yes)NoNoNoNone2240SA200 × 234 mo (yes)NoNoNoNone2349SS200 × 2144 mo (yes)NoNoNoNone2469Sjögren200 × 221 mo (yes)NoNoNoNone2545SLE200 × 236NoNoNoNone2642SLE200 × 278 mo (yes)NoNoNoNone2732UCTD200 × 238 mo (yes)NoNoNoNone2837Sjögren200 × 280 mo (yes)NoNoNoNone2942UCTD200 × 284 mo (yes)NoNoNoNone3048UCTD200 × 2180 mo (yes)NoNoNoNone3133UCTD200 × 210 mo (yes)NoNoNoNone3253SLE200 × 2140 mo (yes)NoNoNoNone3339UCTD200 × 22 mo (yes)NoNoNoNone3455SLE200 × 29 mo (yes)NoNoNoNone3537UCTS200 × 28 mo (yes)NoNoNoNone3638SLE200 × 218 mo (yes)NoNoNoNoneHCQ, Hydroxychloroquine; SA, seronegative arthritis; SLE, systemic lupus erythematosus; SS, systemic sclerosis; UCTD, undifferentiated connective tissue disease.∗ In the last 2 months. Open table in a new tab Table IIISurvey's main resultsPatientsNo.Mean age, yDose of HCQMean duration, moHistory of respiratory symptoms or fever,∗In the last 2 months. No. (%)Exposure to people with respiratory symptoms or fever,∗In the last 2 months. No. (%)Exposure to established COVID-19 cases, No. (%)Dermatologic3055.5200 mg/d14.21 (3.44)1 (3.44)0 (0)Rheumatologic3646.16200 mg 2×50.10 (0)0 (0)0 (0)HCQ, Hydroxychloroquine.∗ In the last 2 months. Open table in a new tab AGA, Androgenetic alopecia; DLE, discoid lupus erythematosus; FFA, frontal fibrosing alopecia; HCQ, hydroxychloroquine; LPP, lichen planopilaris; RA, rheumatoid arthritis. HCQ, Hydroxychloroquine; SA, seronegative arthritis; SLE, systemic lupus erythematosus; SS, systemic sclerosis; UCTD, undifferentiated connective tissue disease. HCQ, Hydroxychloroquine. We reviewed 66 patients, 30 dermatologic patients (8 men and 22 women; median age, 55.5 years; medium duration of HCQ treatment, 14.2 months; range, 3-36 months) and 35 rheumatologic patients (5 men and 30 women; median age, 46.1 years; medium duration of HCQ treatment, 50.1 months; range 2-240 months). Overall, 65 of the 66 patients (98.4%) in treatment with HCQ had not developed fever, sore throat, fatigue, cough, or dyspnea in the previous 2 months. One patient had reported a temperature of 37.2° C for only 1 day, without any other associated symptoms. Mostly, the treatment was well tolerated, without related adverse events; only 2 patients described a brief episode of visual impairment. These patients were suggested to have an examination of the ocular fundus, beyond the regular 6-month ophthalmic follow-up already performed. HCQ has immunomodulatory properties and an attractive adverse effect profile.2Yao X. Ye F. Zhang M. et al.In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [e-pub ahead of print].https://doi.org/10.1093/cid/ciaa237Date accessed: April 26, 2020Google Scholar It could contribute to the suppression of the cytokine release syndrome responsible for the progression of COVID-19 to severe clinical forms through several mechanisms, including (1) reduction of T-cell activation and differentiation, (2) decreased production of cytokines by T cells and B cells (eg, interleukin 1 and 6 and tumor necrosis factor), and (3) attenuation of proinflammatory signaling pathways activation. Interestingly, HCQ and chloroquine inhibit receptor binding and membrane fusion, 2 critical steps required for cell entry by coronaviruses.3Zhou D. Dai S.M. Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression [e-pub ahead of print].https://doi.org/10.1093/jac/dkaa114Date accessed: April 26, 2020Google Scholar However, HCQ offers advantages compared with chloroquine, including a better clinical safety profile, possible higher daily dose, and fewer pharmacologic interactions.1Liu J. Cao R. Xu M. et al.Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.Cell Discov. 2020; 6: 16Crossref PubMed Scopus (1501) Google Scholar,2Yao X. Ye F. Zhang M. et al.In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [e-pub ahead of print].https://doi.org/10.1093/cid/ciaa237Date accessed: April 26, 2020Google Scholar,4Patrì A. Fabbrocini G. Hydroxychloroquine and ivermectin: a synergistic combination for COVID-19 chemoprophylaxis and/or treatment?.J Am Acad Dermatol. 2020; 82: e221Abstract Full Text Full Text PDF Scopus (70) Google Scholar In our study, no patient already in treatment with HCQ developed symptoms suggestive for SARS-CoV-2 infection, although Italy is currently the third-most infected country in the world. Limitations of our study are the low sample size and the absence of exposure to established cases of COVID-19 in the interviewed patients. Further studies on larger samples are needed to assess the possible protective effect of HCQ on SARS-CoV-2 infection. We recommend extending this kind of survey to all patients actually in treatment with HCQ, possibly stratifying them according to residency, posology, other ongoing systemic treatments, comorbidities, and starting prospective observational study for a more extended period (4-6 months). The in vivo demonstration of prophylactic efficacy of HCQ could be a revolutionary result to prevent the transmission of the virus, until the development of a vaccine.